Wearable Continuous blood pressure monitor technology is finally here
At last, a continuous blood pressure monitoring wearable arrives
Continuous blood pressure monitoring through a high quality wearable device is now possible. In our post today, we’ll take a detailed look at the latest wearable continuous blood pressure monitor from our collaborators at Aktiia.
Your blood pressure can be measured 24/7 wearing and data transferred to your app for easy monitoring
Monitoring your blood pressure is an absolutely pivotal part of your longevity strategy. After all, cardiovascular disease, including heart attacks and strokes comprise the most common cause of death for both men and women, globally.
And you guessed it, high blood pressure is one of the top risk factors for cardiovascular disease, as well as for kidney disease.
However, there are several challenges for blood pressure monitoring, which make it difficult to appropriately manage your risk. The most troublesome is the relative lack of blood pressure measurements; you may only get a few such measurements a year at a doctor’s office visit.
Blood pressure constant monitor technologies have not historically been used. For nearly everyone, if you do decide to monitor your blood pressure at home, you will still only manage to get a few measurements per week or per month, if you are diligent. It is also very important to complete these measurements in a controlled and routine fashion.
This data shows the different ranges of blood pressure in adults and how varied it can be.
Healthy blood pressure ranges were set by a foundational research study call the the SPRINT trial, completed in 2015, and are pictured here. Comprised of a systolic (SCP) and diastolic (DBP) blood pressure measurement, respectively representing the pressure of when the heart muscle contracts and in between beats.
Continuous blood pressure monitor wearables are a new technology option, if you’re serious about your longevity. And you’ll want to stay in the ‘normal’ range, to lower your risk of potentially fatal disease. However, a shockingly high number of people have elevated blood pressure. In the United States, for example, nearly 50% of adults have stage 1 or stage 2 hypertension. Even more concerning, as we will learn in our interview today, half of those individuals don’t even know it.
Continious Blood Pressure Monitor Technologies
For these reasons and more, we are very excited to introduce the latest in continuous blood pressure monitoring from our partner’s at Aktiia. Consider the following statistic from their website:
“Hypertension is the epidemic of our time. Hypertension affects 1.3 Billion people and is the leading cause of heart attacks and strokes globally.
Such statistics are again, quite shocking. And the primary barrier to doing something about this epidemic level of high blood pressure around the world, is making it easily accessible for more people to monitor their blood pressure closely and easily.
The state of the art in continuous blood pressure monitoring wearables - the Aktiia 24/7 system. Worn on the wrist, tracked in an app. Monitor your blood pressure all day and all night without any annoying cuff squeezes.
At Aktiia, they have developed a completely wearable solution which can monitor your blood pressure without constantly wearing a blood pressure cuff (as in “continous blood pressure monitoring cuff” but without the “cuff” part, just what we’ve been looking for!)
If you’re new to Longevity Blog, you’ll quickly learn it is our role to introduce you to novel longevity technologies like this one, and guiding you on how to choose the most effective solutions for extending your own healthspan.
We love to get deep into the details with the founders and lead scientists at longevity tech companies to help you cut through the marketing and onto what really works.
Without any further delay, let’s hear from the Chief Medical Officer at Aktiia, Dr Jay Shah, who is a cardiologist with 15+ years of medical expertise and leadership in healthcare and is a wealth of knowledge on the topic of blood pressure monitoring.
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with Aktiia, we have a negotiated an industry leading 10% off coupon code for our readers.
Use the code ‘longevityblog’ at checkout!
This interview was conducted in October 2023 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Aktiia Enables Continuous Blood Pressure Monitoring with a Wearable
Longevity Blog (LB):
Jay, thank you so much for joining us on Longevity Blog today, we are really interested in your novel piece of technology that allows continuous measurement of blood pressure. You are the Chief Medical Officer at Aktiia and you are here to tell us about that technology. Thanks for joining us.
The status quo in modern medicine is blood pressure measurements taken by a cuff on the arm, sometimes there is still a stethoscope involved, and is only done once or twice a day at most. However, longevity technology has advanced and there is now the ability to measure blood pressure continuously.
We are really curious to know upfront - what is the most interesting thing that measuring blood pressure continuously reveals versus it being measured just once or twice a day?
Dr Jay Shah (JS):
It comes down to the main reason that elevated blood pressure actually causes death and disease to your body - BP does this over long periods of time.
Taking one measurement at one moment, at one point in time, maybe once or twice a year, really does not allow any one physician, person/patient to understand what are their blood pressure trends, fluctuations, consistency, over long periods of time, over weeks, months, and years.
In fact there is no current or traditional technology that allows us to do that until very recently and that is really at the heart of what Aktiia does. Our central perspective about blood pressure is that consistently optimising blood pressure over long periods of time is how a person can mitigate the risk of blood pressure driven diseases.
To do that, you need a tool that allows you to consistently assess, look at, manage and optimise your blood pressure over long periods of time.
Blood Pressure Constant Monitor to Reveal Masked Hypertension
LB: The reason behind this, there is this word called 'hypertension'. Hypertension is referring to systolic and diastolic blood pressure measurements above a certain range that we have established through clinical research, that is the healthy, borderline and unhealthy ranges.
To be above the healthy range, you are creating the risk that you are talking about. For many people, they are unaware they have hypertension. There is this concept called “masked hypertension”. What does that term mean? And what is the approximate percentages of adults who have masked hypertension?
JS: Masked hypertension is a term that refers to situations where people have normal appearing blood pressure in the physician's office when it is checked by a nurse or a physician. But at home, which is where we spend 99.9% of our lives, 'in the at home environment', they have higher than normal blood pressure.
In effect, it is essentially missed. People can go years, decades having higher than normal blood pressure, and that is what is called masked hypertension. That is about 15% of the population who have hypertension.
Another version of that is called “white coat hypertension”, which is sort of the inverse, where someone has high blood pressure in the clinic, so the physician and patient get worried, but actually the blood pressure is normal at home.
High blood pressure often starts fairly early on in life - in our 20's, 30's and 40's. Precisely during the decades where we are the least aware of our own health, the least proactive generally.
“Only after years and decades, for many reasons, and not just masked hypertension, but for many reasons, high blood pressure often goes undiagnosed. Over that period of time is really when blood pressure really starts to do its significant damage.”
How to Sleep with a 24 hour blood pressure monitor?
LB: There are a lot of variables that are involved in an individual’s blood pressure. This is known, this is not a surprise. For quite some time now, there have been options for using an 'ambulatory' or '24 hour' blood pressure monitoring device to get a full day or maybe a few days of blood pressure data. Even Though that has been available for quite some time, there is not very much uptake.
Why don't we see more people using continuous blood pressure monitoring data?
This data shows the difference between using a 24/7 monitor compared to the normal ambulatory device. You can read the study for yourself here.
JS: There are several reasons.
First of all, it's dramatically cumbersome, it's a real pain to use it. There are reimbursement issues in many countries where it is often not paid for or not paid very well, for a physician or health care system to actually do it. Which of course limits the motivation in some ways.
Even if they did, or even if someone did use a 24 hour ambulatory blood pressure monitor, it's still a regular cuff that stays attached to your upper arm for the entire 24 hours and you cannot remove it, and you have to carry a fairly large box with you for the 24 hour period.
About every 15 to 30 minutes, it will go off. It will inflate, squeeze your arm and take a blood pressure measurement, even when you are sleeping.
For all those issues and reasons it is not reused very commonly outside of usually highly specialised hypertension centres or academic institutions, or some other select sort of health care centres.
Continuous Blood Pressure Monitor Wearable Data
LB: It certainly sounds quite uncomfortable, but the data it yields certainly would be much more insightful than a single point measurement?
JS: Remember, it's 24 hours and generally it's not repeated on a yearly basis, or every six months or every three months, it's generally done once and usually to answer a specific question.
The benefits of being able to share the data with your health practitioners will help with the longevity of your health journey
For example, if a physician is confused about what is this person's true blood pressure they suspect white coat hypertension, masked hypertension or some other confusion about what this person's blood pressure is, then that is the scenario where we where we might order a 24 hour ambulatory blood pressure monitor and it is done almost exclusively through physicians, as you need a prescription for it.
Even if you did it, it is still only for a single 24 hour period. And as you just said, blood pressure fluctuates continuously, day by day, even changes week by week, it might change month by month.
If diet changes, if your weight changes, if your alcohol intake changes, if you change medicines, if you change all the other factors that affect your blood pressure, that pattern changes.
There have even been studies where the same person repeats the 24 hour test three months apart where there can be up to a 40% variability in the readings. So it is still a snapshot, usually one day's worth of data.
What is the best continuous blood pressure monitor
LB: To summarise, we hear there are three real barriers to greater uptake of 24 hour ambulatory blood pressure measurement. One is, you have to go to your doctor to get it. Second, there is the cost barrier and whether or not that device costs you out of pocket. Third, it is particularly cumbersome and not very comfortable.
Elegant Swiss Design which you charge and wear it all day long. The Aktiia 24/7 system sits on your wrist comfortably, watching the blood surge through your capillaries to create highly accurate estimates of blood pressure.
This brings us nicely to discussing the solution that Aktiia have developed in their very unique combination of a cuff, a bracelet and an app that allows us to monitor blood pressure continuously.
And when we say ‘continuously’, that’s important because we are going into a completely new space, where we have genuine continuous measurement. What does that enable for everyday at home use? What might we learn from this data?
JS: It is easy to use, it's simple, it's an easy to use wearable, you just put it on your wrist and you set it and forget it. Once every month you have to do a calibration step that takes about 10 minutes driven through the app and using the cuff and that is about it.
You just have to keep it charged, wear it - and it has the form factor of elegant Swiss design. It enables you to just not have to think about the act of taking blood pressures. Typically, with any device, traditional cuff you have to think about it, it is an active process, you have to sit down, you have to create a space for yourself, you have to sit in the right position, have the right environment, do all the things that you are supposed to do to take an accurate cuff measurement.
With our device, it is all built into the programming that it takes accurate measurements at the right time, and it is done for the user.
24 hour blood pressure monitoring versus continuous blood pressure monitoring
LB: How many readings does it take per day?
JS: On average, you get about 27 readings per day. It's not taking every minute, because there is too much motion of the wrist to take accurate readings and other other limitations. On average it takes readings slightly more than once an hour.
Remember going back to our primary perspective is that consistency of blood pressure over long periods of time is really what we are trying to solve for. What is more important than one reading, is to compile hundreds and thousands of readings over long periods of time, and to really allow you to understand your long-term blood pressure trends.
There are so many things that this type of data unlocks, and the closest analogy that we have seen, and as most most people are now aware of, are continuous glucose monitors
LB: And what is this continuous blood pressure monitoring data revealing?
JS: For the first time with this dataset, approximately 800 data points in a month of blood pressure, you can start to see trends and patterns clearly.
One thing this enables is a personal trial where you do an intervention targeted at your blood pressure and see its effect. You can see that cause and effect much more clearly with the broader, bigger dataset that this technology enables.
Again, one of the cardinal issues with blood pressure management is trying to effect behavior change. There are often seven recommended lifestyle changes for BP, all of which are extremely difficult to do and some medications they can try.
As a physician, I really don't know and neither does that person, which one of those seven changes and which one of the medications is actually going to work best for them. We have no idea. We recommend the same thing to pretty much everybody.
How is continuous blood pressure measured?
Data is the key to being able to monitor your blood pressure which allows you to manage your own health. Extensive validation has been undertaken by Aktiia across 5 separate research papers to assure its accuracy and precision.
LB: We really like this point because it is really valuable to understand what is working for you and there is this opportunity here with this rich data set to do some self experimenting.
Jay before you go on and into that, we want to just ask one or two questions about this technology. You mentioned it is elegant, it is Swiss design, there is a really impressive story here and how this piece of technology was developed.
We are going to talk about how to use it, before we do that, let's talk about where it came from. We are immensely curious.
Your website states there is 18 years of research and development behind the Aktiia technology and that some of that core work came out of novel research done by your CTO, and in his PhD research.
Can you tell us just briefly some of the key milestones that have allowed this technology to come to exist?
JS: It all stems from our two Co-founders, Drs. Joseph Sola and Mattia Bertschi. They met in Neuchatel, Switzerland at an engineering innovation lab called CSEM - the Centre for Semiconductors, Electronics and Microtechnology.
It started in 2003 -2004, before the iPhone was even developed. There was no such thing as a smartwatch. They were starting to use optical sensors to try to derive physiologic parameters. The first thing they did was to go and study and they could measure heart rate. Again, before the smartwatches, and wearable devices.
They developed a way to look at optical signals and derive heart rate from it. Now many, if not most of these technologies around the world eventually licensed some of their scientific work and discoveries.
Continuous Blood Pressure Data: All About the Algorithm
LB: And then they made the leap to blood pressure?
JS: Heart rate was dramatically easier than blood pressure, so they tell me. At that time, they said, wow we have learned a lot about how to look at these sensors and look at these optical signals, what else can we start to learn about? What else can we start to derive? Can we try to derive blood pressure from these data?
That started an 18 year journey. They started with an animal wet-lab, with pigs, studying their arterial physiology, and how the sensors and the optical signals reacted to them. They did it in animal models first and then they did in human models and then they eventually got a working prototype together in about 2017.
This brought them to the point where they thought they could spin it out and commercialise the technology. Five years ago, 2018, they spun out from CSEM, created the company called Aktiia.
Continuous Blood Pressure Data without a Cuff
LB: The core technology behind this measurement - it is not a compression cuff at all. It is not making any noise - this is an optical sensor.
Tell us, how does that technology work? You mentioned understanding arterial physiology, we imagine there is some fluid dynamics in there. Trying to guess pressure changes based on estimated dilation and contraction, the diameter of blood vessels or arteries, veins, etc. Can you give us a bit of insight into that?
JS: The way it works is it takes these lights that are the two green LED lights on the back of all of what you see most smartwatches. There is nothing actually proprietary about the Aktiia hardware. It has two LED lights and an optical sensor and a three way accelerometer.
What it does is it shines those lights into your skin into the capillary bed, the tiny vessels of that are just underneath your skin and it gets a reflection back. That reflection back into the optical sensor creates a a waveform similar to an arterial waveform - not quite the same but similar.
The devices takes about 30 to 50 waveforms, compiles them together, and then they are sent from your device to your phone via Bluetooth, and from your phone to the cloud via the Wifi connection or cellular connection.
In the cloud that is where the algorithm that they have developed and continue to refine over almost 20 years now, goes to work on that optical sensor data. They were able, after all this time in discovery, to build an algorithm that picks out the salient features of those waveforms for them to be able to derive accurate blood pressure and heart rate, and then delivers that data back to your app as blood pressure heart rate data.
You can't feel it, as you said correctly, you can't feel when it's taking a measurement, there's no cuff and there is no squeezing.
“There’s no cuff and there is no squeezing. ”
LB: There is an important step in this where there is a cuff, and I wanted to just make sure that it was clear what that cuff element on your website product page represents.
You might think I have to wear that, but no, you are doing a once a month calibration. Where does that fit into enabling the algorithm that you just described?
JS: The simplest way to describe it is it puts the numbers in terms of millimetres of mercury. That is the only thing that is missing from the algorithm is that it derives a number and it can use these waveforms to track changes, but it needs something to provide results in units of millimetres of mercury. It's just for that once a month calibration step.
Aktiia is the Best Continuous Blood Pressure Wearable with the Science to Prove It
LB: This device has actually gone through all of the required steps for regulatory approval in several regions. There are five clinical trials now completed with the technology, some of which you are the co-author on, which are dedicated to the validation of this device.
Can you give us a few bullet points around how we know this device is both accurate and precise with these continuous measurements?
JS: All blood pressure devices in countries are regulated medical devices. In all the markets that we are in, we have to have regulatory approval. And regulatory approval generally means that you have to prove that your device, whatever it is, is accurate as compared to a reference device, some standard other device that is well accepted and has proof for.
We have regulatory approval across the EU, UK, Canada and Australia and New Zealand. When we do our validation studies, we don't compare ourselves to a standard automatic upper arm cuff, because the range of error of standard upper arm cuffs is actually fairly wide.
Monitor your blood pressure 24/7 with the elegant wrist band and data collected while you sleep
We run our own, highly rigorous validation protocol in Lausanne, Switzerland at the University Hospital, in their hypertension specialty lab.
Our standard reference is called 'double auscultation'. What the traditional “auscultation method” means is that the observer is using a stethoscope to listen to the arterial sounds to measure the blood pressure using a cuff.
We do that, but with two observers at the exact same time with a bifurcated stethoscope. Two observers are listening at the exact same time to a patient using an electronic mercury column to determine the blood pressure value. They have to agree within five millimetres of mercury or less on every reference value.
That is determined as the gold standard reference value and that is what we are comparing to. So that is how we have done all our validation studies across all the body positions where we have validation data and that is how we have gotten the CE mark across EU in the UK, Health Canada and TGA in Australia.
When will Aktiia become Available in the United States?
LB: People are going to want to know about the United States and this really exciting piece of technology. There is probably only so much you can tell us and it might be speculative, but talk to us about entry to that market. What does that look like for you in terms of a time?
JS: It is probably the most conservative and challenging regulatory body probably in the world, and it is a matter of going through their process and meeting their milestones and the desires that they want to see before they will think about regulatory approval.
There is clearly a pathway forward with them and all I can say is that there are several other parts of the puzzle that have to fall into place for us to have a good chance of approval there. I think that will happen within the next 12 to 16 months.
Can Aktiia Take Blood Pressure Measurements During Exercise?
LB: Thank you for putting it down to a range for us.
You have talked about the technology and how it works and getting these measurements across the day - readers will naturally have questions around what types of measurements they are going to get.
We have two questions for you about certain times a day. The first one is exercise, you mentioned accelerometer in the device and I am assuming that you are not going to get measurements during exercise?
Learn more about cardiovascular disease prevention with this post about four blood tests that can help you manage your risk.
JS: The first thing to understand is just what happens to your blood pressure when you are exercising. Physiologically, when someone exercises your blood pressure generally goes up, normally. It goes up above the standard reference ranges of a resting blood pressure, and that is normal, in most cases. Sometimes it goes up excessively, but most of the time it goes up normally.
Then immediately after exercise, generally, it actually dips below your normal resting blood pressure, and then comes back to your normal. These are the sudden, what we call acute changes of physiologic exercise. During exercise of most types, if not all, not maybe not all, but most types, the Aktiia system will not take a measurement.
The reason for that is, one is that the accelerometer when it detects significant motion of the wrist is the first and primary filter of quality for motion, and it just tells the device, no, you are not going to take a measurement.
The rationale behind that, is that the optical signals in the capillary bed at your wrist, are highly sensitive to and degraded with significant motion. We do not want to analyse bad data.
If someone is exercising, you are not going to get measurements during that time, but you will get measurements before and after, and all it requires is about 30 seconds of stillness of the wrist.
Aktiia and Continuous Nighttime Blood Pressure Measurements
LB: Thank you Jay, our second question is about nighttime blood pressure measurements. There is actually a significant amount of science dedicated to nighttime blood pressure measurements, in particularit being more correlated to cardiovascular disease risk than daytime measurements.
Very few people will have ever received a nighttime blood pressure measurement, your device clearly is going to enable that. What do these measurements most often reveal?
Some light-hearted blood pressure monitoring fun…
JS: There are many signals in nighttime blood pressure data that you just don't get during daytime. There are clearly certain signals that are more associated with cardiovascular risk. But even with the ambulatory blood pressure monitoring data, which all drives the evidence around this nighttime data, there is not clear knowledge about what to do with all those markers or data points, other than just to know about it.
There are a few things to think about, maybe you can alter medication regimens, sometimes it involves sleep disorders, like sleep apnea, but oftentimes, there is not that much that you can do about it.
One of the things about Aktiia and continuous blood pressure monitoring will enable, is that the data set is so dramatically different. We are working with many universities and research centres around the world to try to understand all possible novel markers that we can get out of this dataset.
Historically we have never really been able to look at blood pressure data in this way, and now all of a sudden, we have this dataset where we can. I think there is a lot more discovery to be done and there are probably many more unknowns than there are knowns at this point.
Data from Continuous Blood Pressure Wearables Enables Personalised Healthcare?
LB: That makes a lot of sense because whenever we start to get continuous data or higher frequency measurements, in many fields of science, we start to see some of those second and third order effects that jump off the page that we didn't see before.
In your answer there, you started to touch back on one of your points earlier that I promised we would come back to, and this was your reference that when somebody comes and visits you in the clinic, and they have high blood pressure, you give them seven things to go try.
Can you tell us what those seven things are?
Eating a healthy balanced diet is one of the best ways to keep your blood pressure under control
JS: Almost all your listeners could too, because they are so well known. They will say you need to exercise more, you need to lose weight, you will need to decrease alcohol, you need to stop smoking, you need to decrease your sodium in your diet, you need to have better sleep habits, and decrease stress.
But here is the catch - every one of those seven things to a patient to a person is fairly life-changing; these are not easy things to do.
Even increasing exercise to over three hours a week takes an inordinate amount of effort for most people to really adjust their lifestyle. Or if you actually want to reduce your sodium in your diet to the recommended value of 1800 to 2300 milligrammes of sodium a day, it is incredibly difficult, because sodium is in almost all foods.
And these blanket recommendations are completely generic. As an example - only about 50% of people are are salt sensitive. Meaning for fully half of the people that we tell to lower their sodium, it will not make a difference in their BP. There is currently no way to know who is salt sensitive and who isn't. We do not know, physicians do not know, the patient does not know either. And there is no way currently to figure it out.
Using Continuous Blood Pressure Monitoring to Select the Right Blood Pressure Medication?
LB: The same thing could be said about testing blood pressure medications, correct? There is usually trial and error involved in finding the right medication to control a person’s blood pressure and balance that with any side effects.
JS: All expert hypertension bodies recommend two pathways of medications. Either you are 55, or above, or 55 or below, or you are black or non black. Based on those two things, you get a regimen of blood pressure medications, and it is the same standard medication for everyone.
We don't really know who is going to respond more significantly to one medicine or another. All the evidence that has ever been done on blood pressure medications has been done on a large scale, population based way. So we do not know how individual people respond to them.
This is another example of how people can start to use individual data from clinically validated wearables to say, okay, that medicine really did not work, but this second one really did work. Maybe I can just get away with one instead of two, and really start to dial in on their medication regimen in a more precise way and a more individualised way.
Dr Shah’s Personal Approach to Longevity
LB: We love this because you've just gone through and describe self experimentation, you have done that from a doctor's perspective, from a technology entrepreneurs perspective, that's really refreshing and fun.
Clearly, the Aktiia system is going to support our audience with healthfully monitoring and improving their blood pressure with lifestyle changes and medications in collaboration with their personal doctor.
In building a longevity strategy, each of us has to pay attention to what works for us and what our risks are. In closing, we would like to hear from you personally, one or two things that you do to look after your own longevity, if you don't mind sharing?
Dr Jay Sharing lives a balance lifestyle including regular exercise and social interaction. This is one of his walks in Switzerland along Lake Geneva.
JS: The two things that I try to focus on as much as I can - exercise is the primary one. I always try to get as much exercise as possible throughout the week. I try to get at least three, four hours of exercise in.
Second, and I don't know the science behind it, but I think one of the most important things to living a long and fulfilling life is social interaction, laughter, community, and I think that over the last few years, I have really tried to be proactive and purposeful about finding a place in a community, neighbourhood, people and family around me. This really gives me a sense of contentment and fulfilment.
I think those are the two things that I really tried to focus on more than anything else.
LB: We really appreciate you joining us on the Longevity Blog here for the interview today. We hope to hear more about when this device will be available in the US. Thank you.
JS: Thanks very much for having me! It's been a pleasure to be here.
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Can Tru Diagnostic Finally Answer: Why am I aging so fast? An interview with Ryan Smith
Why am I aging? Why am I aging so fast?
Why do I feel older than I am? Why am I aging suddenly?
Sometimes aging can catch up with us very quickly, leading us to ask questions like these ones.
The years add up, and we don’t feel the vigour and vitality we are used to. Most of us assume, there isn’t much we can do about it. Aging is inevitable, after all?
You may be new to the longevity technology scene, most people are. Or you may be a longevity hacking legend, who thinks they know everything about how to slow the aging process.
It doesn’t matter which side of the spectrum you find yourself on, there is an exciting new development in the field of biological age testing which can help you answer the all important question…
Why am I aging?
In this post, we are going to review recent updates to TruDiagnostic’s biological age test, which help to answer:
Why am I aging?
If you’re new to biological age testing, there a few deep dive posts you can read on Longevity Blog, perhaps start here or here.
To summarise them in one sentence, it has become possible to measure how old you are biologically over the past few years and there are now dozens of tests for doing so.
But to date, none of them could give you concrete details on the why behind your biological age score.
You might be biologically older or younger than your chronological age (connected to your birthday, the number you celebrate each year).
And beyond ‘exercise more, eat better, sleep more, stress less, don’t smoke, avoid pollution’ - there really hasn’t been much you can do about the aging process.
Until Now….
Tru Diagnostic: Getting to the “Why” behind “why AM I AGING?” (and what to do about it)
Aging is ridiculously complex. Our approach with the OMIC Age clock has been to consolidate information from the entire system and taking a more complete look at the full picture of biological aging…
One of the big things that we have shown with this new aging clock is that it is really the most predictive of every type of age related outcome.
This quote is from our interview below with Ryan Smith, Co-Founder at Tru Diagnostic. We’ve previously introduced Ryan and interviewed him in a two part review series, which you can find here - Part 1 and Part 2.
Our role here at Longevity Blog is to dive into the why and how behind such claims. We aim to dig deep and find the real answers behind the marketing slogans.
We interview founders and lead scientists at longevity tech companies and present you the raw, unfiltered conversations that get straight into the answers.
Today, we’re going to explore some of the key updates to the TruDiagnostic test kit, including the powerful new research efforts behind its development.
What just become possible is truly impressive, and may even be groundbreaking into a new era of biological age testing (namely finally answering - why am I aging so fast?).
Let’s do just that.
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with Tru Diagnostic, we have a negotiated an industry leading 12% off coupon code for our readers.
Use the code ‘longevityblog’ at checkout!
This interview was conducted in October 2023 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Tru Diagnostic “OMICmAge” Update
Longevity Blog (LB):
Ryan, thanks so much for coming back to join us again on Longevity Blog, we are really excited to talk to you about some updates that Tru Diagnostic has to their biological age estimates.
The new algorithm is called “OMICmAge” which you are pronouncing as “OMIC Age”. This algorithm is multi “omic” in nature and has demonstrated some very impressive results particularly in predictive capability for mortality and health outcomes.
We are going to break it down - let's start first with what does it mean to be “multi-omic”? And what is an “omic”?
Ryan Smith (RS):
Generally, we would call these “omics” different levels of measurement that are trying to replicate what happens naturally in our body from a stepwise process.
This starts with things like genomics, everyone's familiar with the genome. That would go to the epigenome into things like transcriptomics, metabolomics, and proteomics. These are different ways to measure physical things which are happening in the body.
Bringing together data from all of your “omes” provides a more comprehensive picture of your biological age and why you are aging.
The reason that this is important for aging, is because aging is ridiculously complex. Our approach with the OMIC clock has been to consolidate information from the entire system and taking a more complete look at the full picture of biological aging.
LB: Just to make sure we get this really clear, you mentioned a few different types of “omes”. First genome and epigenome, our audience is pretty familiar with those.
You probably start to lose some readers when you mentioned proteome or metabolome. Why don't you briefly explain what either of those are just as examples?
Tru Diagnostics New Aging Clock Tests More of Your Individual Biology
RS: In the molecular biology world, we have being transcribed by the ribosome, which then create the proteins or peptides that make up the infrastructure of the body. That's what we call proteomics.
Metabolomics is the study of all the small molecules or metabolites within the body. One example of important metabolites are our hormones or neurotransmitters.
Even if you might not be familiar with proteomics and metabolomics, you are certainly familiar with the spectrum of biomarkers that influence disease progression or performance.
LB: This involvement of these different “omes”/”omics” provides a lot more information about what's happening in the body as it is aging. Including this additional information produces a great result - the predictive capability for both mortality and health outcomes.
Can you explain the significance of this development?
OMICmAge Can Predict Health Outcomes, Not Just Mortality
RS: One of the big things that we have shown with this new aging clock is that it is really the most predictive of every type of age related outcome.
More generally, if you are accelerated with this biological clock (biological age > chronological age), you are going to be at more risk of all negative health outcomes than you would be if you were accelerated with the same amount (e.g. +1 year) than any other clock (i.e. any other biological age test).
Pulling together so many sources of information, allows the new OMICmAge algorithm to be incredibly predictive of both mortality (death) and disease outcomes (what age related illnesses you are most likely to get).
LB: The last few sentences that you described are really exciting, and something we will converge in on after a few more questions here. One thing we want to go back to, in addition to this “omic” part of the clock name - we also have an “m” in there, which stands for methylation.
This part of the background development on the new clock comes from a broader collaboration, that is actually really impressive. You have pulled in some of the best researchers on this topic in the world.
We would like to just briefly hear from you about that collaboration.
Tru Diagnostic Partnered With Harvard to Bring in the Leading Science
RS: Proving outcomes about longevity and disease requires following up patients for 40 or 50 years to see what is happening to them. Are they developing disease? Are they dying? When are they dying and what are they dying of?
All that information is incredibly important, but also incredibly difficult to get because really, you had to start a lot of these studies or these data collections a long time ago. In order to do that type of analysis, which we know we needed, we had to work with a biobank.
TruDiagnostic’s dramatic leap ahead of the competition on biological age analyses has been made possible by collaboration with world class researchers and datasets.
Dr Jessica Lasky-Su ticks both of these boxes - an Associate Professor at Harvard Medical School with access to the incredible biobank data at Brigham’s Womens Hospital.
We chose to work with Brigham Women's Hospital and researchers at Harvard. Dr. Jessica Lasky , was our main collaborator on this, along with her postdoctoral student (Dr. Ching Win).
We were able to get samples that had been taken 50 to 40 years ago, and then do our analysis on those samples.
LB: An important part of which was methylation data, the “m” in the OMICmAge clock?
RS: To your point about methylation data, it actually saves greatly on costs. Biological aging is very complex and to measure all of those different “omes” in individual aging it is prohibitively expensive.
Of the 5000 patients in our cohort, costs for testing were $9,000 to $10,000 (USD), to quantify all of those different things at every single level. It's way too expensive.
We knew we had to consolidate data from all those ‘omics’ into a single test which can be done at a much lower price and at scale.
With DNA methylation we can actually predict the “omic” data. Meaning we can quantify things that previously you could only do through advanced proteomics and metabolomics.
OMICMAGE Uses Methylation Data to Predict Biomarkers of Aging
Through measuring your DNA methylation (epigenome), TruDiagnostic can now reveal how different systems in your body are contributing to your biological age.
In short, the “why” behind why you as an individual are aging is starting to be revealed.
LB: Let us jump in there and just break down some really important parts of what you just said.
The omic data you were describing at the opening of the interview is a rich source of information from all different systems in the body. However, it is very expensive to measure those things directly, but they are very indicative of aging outcomes. So we want that information.
Now, what Tru Diagnostic and your research collaborators have made possible, is using the DNA methylation data to make estimates or predictions of omic information that is driving aging - this is a really big advancement.
RS: That is exactly it. We are starting to understand the why of biological aging by incorporating more detail about the things that are driving the process. In our study we used methylation to predict other values.
Right now we can use methylation to predict things you would get at a typical doctor's visit, things like your HbA1c for blood sugar management, your fasting insulin, fasting glucose, or even your creatinine.
Now we can use DNA methylation to output the things that previously were things you had to go get a blood draw at your physician's office to actually quantify.
See Why You are Aging So Fast (Or Not!)
An excerpt from a sample report from TruDiagnostic. Your DNA methylation data can now reveal the status of key blood markers and how they are contributing to your biological age.
LB: To that point, this ability to use the methylation data to predict different biomarkers and provide information about the “why” behind individual aging - there are new reports that are going to be accessible to Tru Diagnostic customers on the 12th of October (2023).
Moving ahead, OMICmAge is going to become your primary biological age clock and this information about these biomarkers will be in the TruDiagnostic reports made available to your customers.
You have offered to show us a sample report with some of this information. Let's pull that up now and walk through some specifics of what information we are able to predict about different OMIC areas of the body with his DNA methylation data.
RS: This is a very robust report, I won't take you through everything. We have about 10 clinical biomarkers, 12 different proteins and 12 different metabolites which we can connect to impacting your epigenetic age.
For instance, we might give you your haemoglobin or your creatinine results, much like you might see on a blood based lab. The real important part here is that we can also tell you how it is contributing to either helping or hurting your biological aging process.
For instance, probably the most protective factor in this particular individual (see image) is serum albumin. Serum albumin is a protein which can bind a lot of other things in your body and for people who are very interested in aging, this is one of those factors, which tends to decrease in decline with age.
We also know that red cell distribution width (RDW) and HbA1c are probably the factors in this particular patient, which are driving their aging process the most.
Another excerpt from a TruDiagnostic OMIC Age test report. Key blood markers which are contributing to an individual’s aging. Here, low blood Albumin is a key target for intervention. Low levels are making this individual biologically older than the would otherwise be. Red cell distribution width (RDW) on the other hand, is looking healthy.
Why I am Aging? Then, What do I do about it?
LB: This seems to be directly related to the term precision aging - we have heard it in a few other places.
That concept is broadly representing what you just said - namely personalised outcomes and understanding aging for the individual.
Carotenediol also goes into the name Lutein, which people already often take as a supplement.
Through the work on the OMICmAge clock, its importance in aging has been even further emphasised. It is a key metabolite for biological age.
You have shown some examples there. Let's talk in a little bit more detail about what this means for an individual's longevity strategy for their own effort to stay helpful and youthful for longer.
You mentioned that we can use that report to find targeted opportunities for improving biological age. Could you give an example from this report that reveals a marker that is very important for that individual and what action would they take to improve their biological age?
RS: I think that one great example is a metabolite. These are really good examples because a lot of the metabolites in your body are based off of things you eat or supplement. Carotenediol also goes into the name Lutein, which people already often take as a supplement. People might be familiar with it for some of its eye health benefits, which is probably most common for.
Lutein and other Carotenoids are a pillar of longevity. With the OMIC Age test from TruDiagnostic, you can understand how your diet (and supplement) strategy are working (or aren’t working) to improve your biological age.
We included Lutein in our OMIC Age prediction through algorithmic selection. We find that if we wanted to predict death accurately, that Lutein (carotenediol) was one of those metabolites which was highly influential in terms of predicting longevity as an outcome.
This is a really good case example because we also know that if you supplement with carotenoids, you start eating more things like leafy green vegetables like spinach, or kale or, or carrots or yellow peppers, you can actually increase that carotenediol level within your plasma.
And that will actually change our biological age prediction through changes in DNA methylation. That will then take your overall biological age down.
OMIC Age and Self-Experimentation
LB: What is the sensitivity in or I should say, responsiveness of the algorithm to change that you just mentioned? How long do you think a user would have to run that self experiment? They are going to measure with a Tru Diagnostic test, they are going to make a dietary or supplement change, maybe both and test again. What does that testing protocol look like?
RS: That is a really good question, and to be honest with you, we are not quite sure yet.
I think quite frankly, it might be different for many of those different predictors. For instance, your HbA1c is a really good example, because it behaves a little bit like methylation biomarkers behave, which is sort of a three month running average.
Traditionally, we only recommend testing every six months. But we've seen even some of these epigenetic biomarkers change effectively, in as little as eight weeks.
LB: So we are still looking at six months as the approximate timeline for self experimentation, that could change because there is a lot here that is new and unknown.
Just come back to that example, if somebody wanted to make a dietary shift or dietary change, or supplementation change, and then measure before and after, we are going to still go with the guidance of approximately six months at this time for measuring before and after. Do you agree with that summarization?
RS: I think on a casual basis that is what I would recommend. In shorter periods of time, you might have some transient changes that don't reflect the true biological aging changes and so the longer period of time that you are doing intervention, the more confident we can be that the result is correct, and that you are moving in the right direction.
DISCOVERING NEW FACTORS DRIVING AGING
Before you go! Why not dive deeper on biological age testing with TruDiagnostic? Our two part interview with Ryan Smith covers many important basics.
LB: One other thing I wanted to explore before we close off, Ryan - You have actually been discovering new influential factors in aging through this research that were not previously known - please give us an example?
RS: As our ability to predict other things with epigenetic methylation become even more powerful we are going to have even more insights. The metabolite ribitol is one of those examples.
This is a metabolite that is influential in creating the baseline molecules we use to regulate DNA, RNA, or even some of those sugar based pathways.
If you look this up in the literature, you find only two examples about this in PubMed. Although there were very few references to it, we are seeing that it seems to be a very good predictor of mortality.
LB: That's really fascinating Ryan, and we have walked through a great update of what is coming out with this new clock. Soon, we are going to be able to look at some examples from our Founder Nick’s results after the OMIC Age clock comes out.
In closing, we just would like to say that this is really exciting and congratulations to TruDiagnostic and your collaborators for bringing such an advancement to the field!
RS: It is always a pleasure to talk with Longevity Blog. We always have some elevated conversations, which probably yield a lot of questions. If anyone has any questions, feel free to reach out to us directly at TruDiagnostic.
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Understanding One Truth 818. Is this premium product worth the price? An interview with Rachael D’Aguiar
One Truth 818 Review. What is it?
As we’ve previously discussed, the market for ‘anti-aging’ skincare products is absolutely huge. There are so many options for looking after your skin, nearly all of which claim to be ‘anti-aging’.
And of course, we understand why this is the case - looking younger is worth its high price, to many. And those who have the funds to spend, well, they tend to look the most youthful, and thus the premise already proves true. You can look younger - if you have the money to spend on it.
And that’s where we come in. We believe that your aesthetic age is an investment, worth your hard earned dollars. But you have to be smart about it! We help you do just that.
Today, we’re going to review the company OneTruth 818, going much more than skin deep, to help you answer the question - is this premium price point product worth your hard earned dollars? One Truth 818 certainly makes the claim that their products will do the job, consider their headline website statement (at the time of writing).
Some of the reported benefits of using One Truth 818 are lifting of the skin, particularly eyelids and the neck. In this post we interview their Co-Founder to find out more.
“Unleash the enzymes that repair DNA damage. Scientific skincare that truly reverses the signs of ageing.
As time passes by, the Telomeres at the ends of our Chromosomes get shorter. This shortening is what causes us to age. But there is an enzyme within your genes that can undo the ageing process, all you have to do is activate it”
At Longevity Blog, we help you sort through the hype and get down to the real results you want, by helping you to test before & after results yourself. Our job is to ask targeted questions of the founders and lead scientists at longevity tech companies, to help direct your personal investment into your own longevity strategy, effectively.
Once again, today, we are going to do just that.
One Truth 818 Reviews: What is ‘Scientific Skincare’?
In our review of OneTruth 818, one thing that really jumps out at us are the marketing claims that the product is rooted in solid science.
We of course love the sound of the term ‘scientific skincare’; there simply isn’t much science behind most skincare products at all. Most of the science that is in place is basic safety testing, uses animal models and doesn’t actually evaluate efficacy in human skin tissue directly.
But, upon some detailed investigation, One Truth 818 does appear to break this mould. And in our interview today, we are going to hear from Director and Co-Founder Rachael D’Aguiar about the science that backs their unique product line.
A foundational part of the multiple claims by One Truth 818 is the activation of the gene which produces telomerase.
Telomerase is an enzyme which repairs/maintains telomeres, which are aprotective ends on the chromosome. And it is the chromosome which contains all of the DNA information required by your cells to healthfully replicate and function.
Notably the discovery of telomerase won a Nobel Prize in 2009.
Telomere dysfunction is now known to be one of the causes of aging. Within the skin, increasing amounts of evidence are linking telomere ‘attrition’ (shortening) to skin aging, but more research is needed to demonstrate the direct link between telomerase and improved skin health.
What is known however, is that UV damage, so called ‘photoaging’, reduces telomere length as damage from sun exposure is accumulated. More recently, telomere attrition in the skin has been linked to significant increases in skin cancer risk.
So, while more science is needed to have ‘all the answers’, this is common in the longevity technology sphere. As we look out for our long-term health, we get to choose how far ahead of the ‘proven’ science we individually are comfortable to reach.
This is the ‘art’ side of practicing longevity, and is of course exactly where your own self-experimentation fits in. The answer to ‘will it work for me?’ - well, that is of course the only thing that really matters!
And with that, let’s hear more on these topics from an expert on telomeres, skin health and aesthetic age…
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with One Truth 818, we have a negotiated an industry leading 15% off coupon code for our readers.
Use the code longevityblog at checkout!
This interview was conducted in September 2023 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
One Truth 818 Serum Review
Longevity Blog (LB):
Rachael Thank you and welcome to Longevity Blog, we're really excited to hear more about the science behind your product line, your company, One Truth 818. And to kick off, we'd really like to hear from you on what the term “scientific skincare” means to you.
Rachael D’Aguiar (RD):
Absolutely, you know, most skincare products on the market, are not actually based on science, the information comes from regurgitated blogs, or vloggers, and really outdated information, or they'll talk about a new ingredient.
But they don't stop to ask, what's the starting base of this? Where's the science? What does ageing look like in the skin? How do cells age? And then let's go from there. So everything we do, is based on science, not a trend, and not something that we read from someone else.
What is TAM 818?
LB: And to that point, the name of your company is actually based on some science, you've got this number in there - “818”. There's a fascinating scientific story behind where that number comes from. Could you tell us about that?
RD: I can. So we work very closely with Dr. Bill Andrews, who is the molecular biologist who actually discovered this molecule, which we call TAM 818. TAM stands for “telomerase activating molecule”.
Dr Bill Andrews discovered telomerase and is also an avid runner who enjoys ultramarathons.
You can't shove telomerase into your skin. It has to be activated within a cell and used within a cell. But the interesting part is the number 818. That's what people always ask us about.
It's also a nod to Dr. Bill Andrews’ tenacity, because the TAM 818 molecule was the 314,818 molecule that he screened and tested.
All up he actually screened and tested over 400,000 molecules for telomerase activity, this one being the strongest.
LB: That's really a sign of tenacity, as you've just shared and Bill Andrews is clearly a very important figure in the history behind the science and has a relationship with your company.
Could you tell us a bit about Bill and where he fits into One Truth 818 today?
RD: He is an award winning molecular biologist, and he's credited with discovering the gene and the enzyme telomerase, which at the time was touted as the biggest discovery since antibiotics.
It actually triggered the Nobel Prize in 2009 to be given to the people who discovered telomeres, although they discovered them in the early 1980s. So it wasn't until Dr. Andrews discovered telomerase, that it showed the importance of what a telomere was.
Now he's the president of Sierra Sciences with a personal motto “cure ageing or die trying” and he's been nicknamed “Dr. Telomere”. So he really is the authority on everything and all things telomeres.
What are the ingredients in One Truth 818?
LB: The discovery of this telomere activating molecule 818 - it has become a fundamental ingredient in your product line. Naturally, we're all very curious. Now we know this is your IP, this is your secret sauce, but what can you tell us about TAM 818? We're fascinated and curious here, Rachael.
RD: I can tell you what it's not. It's not a peptide, it's not a protein, it's not an amino acid, it didn't exist until we created it. So it can't even be categorised, which probably explains why Bill has been able to test it as being the strongest telomerase activator on the planet by over 300 times.
There are many scientists studying the role of telomerase in maintaining healthy telomere function. You can read more in this article from the Journal Experiential Dermatology.
It is completely safe and non toxic. It's a small molecule so it penetrates the cell. Lucky for me, the very first tests that he did in his laboratory were on human fibroblasts skin cells. So right from day one, we've known it can do for the skin.
LB: Wow, that's really interesting to hear that it's been created or discovered, in a way. What an amazing discovery to find a small molecule that can penetrate the skin, get into the cell and then activate the telomerase gene.
There's an important connection between telomere attrition (the shortening of telomeres) and skin ageing. Could you talk to us a little bit about that connection? The scientific evidence is growing on this topic.
Why Telomeres are Important for Skin Aging
RD: What I am going to tell you here is the complete opposite to what the skincare industry will tell you.
We know that every time a cell divides, the telomeres shorten, and that cell can divide approximately 50 times until the telomere is so short that it can't divide anymore. That cell then becomes a senescent cell.
“I can tell you what it’s not. It’s not a peptide, it’s not a protein, it’s not an amino acid, it didn’t exist until we created it.
So it can’t even be categorised, which probably explains why Bill has been able to test it as being the strongest telomerase activator on the planet by over 300 times. ”
However, if you listen to the regular skincare industry, they will tell you that to have younger skin, you need to increase cell turnover, you need to bring new cells to the surface faster, but this actually speeds up cell division, accelerating the ageing process.
With One Truth 818, it is the complete opposite. TAM 818 has been proven to lengthen telomeres. So when that cell divides, the telomeres shorten, and then the telomerase enzyme is expressed so that those telomeres really lengthen. This means you are undoing the ageing process, reversing the ageing process.
I want your takeaway from me today to be: 'cell division equals ageing'. There is a Hayflick limit, your cells cannot keep on dividing past that. It's telomere shortening, cell division, that drives this.
LB: With this cell division, you are not naming names here, but we'll jump in there and say this is the premise of retinol of retinoids. That's one of the approaches that we could say that you're citing, which is again to take off that top layer of skin bring the new youthful skin cells to the surface.
This takes skin cells through their lifecycle more quickly, thereby accelerating the ageing process. This brings us to an important distinction for One Truth 818 - you are talking about a rejuvenation and about keeping cells that are there healthier for longer.
Transitioning just over to another type of damage to the skin, let’s talk about UV damage. The “photoaging” effect. It is the primary driver of ageing in the skin and there is unique relationship between photoaging and telomere shortening.
Could you introduce our audience to this relationship?
Telomere Attrition and DNA Damage
RD: When you are exposed to UV radiation, you damage parts of your DNA. This includes the telomeres, which are the tips of your DNA, there to protect your DNA.
In my mind, it is actually no different to the other sorts of damage which the skincare industry is intentionally doing to the skin. Ablative laser for example - there is no reason why it wouldn't be the same as the damage caused from UV radiation or other forms of toxicity.
Learn more about the role of UV damage in skin aging in our interview with One Skin CEO Dr Carolina Reis.
These types of damage lead to telomere shortening, and the shorter your telomeres are, the less likely they are to be able to produce collagen, elastin and balanced pigmentation.
The photoaging issue, when it comes to telomeres, it's twofold. The cells are constantly dividing, trying to heal the damage.
It also is damage to the pigmentation cells, which then start throwing more pigment out, which is also an issue of short telomeres. The shorter your telomeres are, the more likely you're going to have pigmented skin.
One Truth 818 Serum and Pigmentation
LB: This is fascinating because one of the primary signs of ageing in skin is pigmentation which is ultimately a defense mechanism. Tell us about more about the relationship between telomere attrition and pigmentation.
Before and after changes of skin pigmentation after 60 days of One Truth 818 serum.
RD: If you look at your children, or someone younger than you, they have collagen, they have elastin, and they have a balanced pigmentation, because they have lovely long telomeres and really functioning cells.
But between those 50 divisions I was telling you about (Hayflick limit), between really long telomeres, and critically short telomeres, you have old age. When those telomeres hit old age and are incredibly short, they can't produce collagen, they can't produce elastin and they will vomit pigmentation on the surface of your skin or they will stop making pigment whatsoever, and you will have white patches.
These are all conditions caused by aged cells. They are not separate things that need separate treatments. If you can re-lengthen your telomeres, and have a younger cell again, it functions like a younger cell again.
Does One Truth 818 improve wrinkles?
Improvements in wrinkle depth from One Truth 818's independent study with Abich Laboratory.
LB: In this exploration of the concept of scientific skincare, your company commissioned a study in Italy with an independent laboratory to test your product on 100 volunteers of widely varying different ages.
There were some really interesting results after just 30 days usage of One Truth 818, and there are two categories that we want to go cover today.
The first is measurement before and after by high quality optical sensors from the company EO Tech. This provided an ability to 3D map the skin and look at the “surface topography” - or simply put wrinkles and smoothness of the skin.
What did this study find after just 30 days?
RD: To my knowledge, the largest scale topical study ever performed on skin, certainly in the field of epigenetics on skin. This is where we found the information about pigmentation, for example. So my background, I come from a regular skin background, I worked as a skin therapist for about 20 years before I came into this.
I had all those beliefs, that all the conditions of ageing were all separate, that they were different issues among themselves.
I was actually really surprised myself at the time, to go hang on what's happening here and to talk it through with Bill, and that is where we understood actually, pigmentation is caused from aged cells.
For the smoothness and wrinkles results you’re asking about - there was a 14% reduction in wrinkle depth and skin roughness decreased by 12% on the forehead, and 11% and nearly 10% in the ‘crows feet’ region.
One Truth 818 Before and After skin elasticity
LB: Thank you for sharing those. As we mentioned, there was second part of the study we were very interested in, which looked at skin elasticity and firmness.
Using a scientific grade “Cutometer” digital cutaneous (skin) probe, which is the ‘standard’ for measurement of elasticity in dermatology - there was some really exciting results in elasticity, and firmness, and in fact firmness improved by 20%, skin elasticity by around 10%.
What is going on with telomeres and skin elasticity and firmness? These are quite significant changes for these measures, and in only 30 days! Clearly something valuable is happening here.
RD: Can you imagine putting something just topically on your skin, and your cells produce more elastin?
The volunteers were between 36 and 65, so they are not naturally going and producing a whole lot of elastin and with elastin, think “elastic”, it is all to do with the tautness and the turgor (skin turgor is the skin's ability of skin to change shape and return to normal).
Any kind of sagging is happening because you have a lack of elastin, so to be able to increase that by almost 10% just by popping something topically on your skin, is absolutely incredible. Just testament to the fact that your cell is behaving like a younger cell again.
OneTruth 818 and Telomere Length
LB: There is quite an exciting story coming together here, Rachael, and in this discussion there has been talk about telomerase, telomeres, scientific research. On this topic, we have a follow-up question:
One of the observed benefits from the One Truth 818 customer base is a notable improvement in sagging skin around the neck.
Do you have any direct evidence of before and after telomere length in this skin that shows TAM 818 is making skin telomeres grow longer?
RD: All of that was done by Dr. Bill Andrews, before we even popped TAM 818 into a skin cream. He was able to say, on his scale of measurement, that TAM 818 was a 16% “HeLa”.
At that level, it should actually reverse ageing and make a cell immortal. We had a molecule that was already tested to activate telomerase and human skin cells.
The Abich laboratory studies we were just discussing really surprised Dr. Andrews and his scientists, as it discovered that telomerase preferentially lengthened the shortest telomeres first, which explains how you get such a visual result so quickly.
OneTruth 818 Before and After Photos
LB: On the topic of visual results, your customers love sending you before and after images. If you were to summarise what you have learned from the users of your product, what would you say the most common observations are?
RD: Lifting of the skin, so particularly eyelids and necks, which are typically very, very hard to have an effect on without some kind of surgery.
The quality of their pores, because everything about the texture of their skin changes. Pigmentation is another - the effects on pigmentation are incredible.
This is a before and after from the One Truth 818 customer base that appears to show significant reduction in wrinkles and improvement in skin thickness below and around the eye.
Trying One Truth 818 Serum Yourself
LB: That's exactly the type of thing that our audience likes to hear, because we are a group of self-experimenters.
The next thing that we want to ask you, building off of what you just shared is, what a protocol would be for self-experimentation.
Our audience want to know, is One Truth 818, worth my hard earned money? Is it worth my investment?
We excel at before and after images for skin longevity. Check out this post for some ideas on how to get quality before and after images for your own self experiment.
Let’s get specific - what product, how many times a day, for how long, and most importantly, how do they see before and after and know - this product is working for me?
RD: I tell everyone to take a before shot - go out into natural light, with no makeup and a totally relaxed face. Notice what time of day it is and take some photos from the front and from the two sides.
The regime, it is the most simple thing that anyone has ever told you to do. Clean your face and then put the One Truth 818 serum on from your forehead over your eyes over your lips and down your neck, that is all.
Two pumps will do the face and the neck.
Longevity Blog is Testing One Truth 818
LB: We actually have a bottle of the serum here (shows bottle), and we have been told that a bottle of the serum at the protocol you just mentioned will last around two months, correct?
RD: 8 to 10 weeks with twice a day.
LB: So just over 2 months, less than three. Thank you.
RD: I do encourage twice daily use, as all of our experiments are done on twice daily use. The more frequently you activate telomerase, the better results.
Don't buy this product and keep it as a once a week treatment, or once a month as a special occasion, you won't see the results you are after, I want you to activate telomerase twice a day to see the results that you're after.
Longevity Blog is testing both One Truth 818 Serum (centre) and the Atomiser (right). Over the course of the 3 months we expect to use 2 bottles of the serum and one bottle of atomiser to complete the self experiment.
LB: That's for the serum and then we also have the atomizer (show atomizer bottle), which spritz on your face across the day, and also you can put it on before you put on the serum. Were would this sit in a self-experimentation protocol?
RD: The atomiser is super hydrating, so if you have problems with hydration, you can pop it on under the serum, and even use it over makeup because it's water based, no oil.
For example, you would use the serum morning and night like I've told you to and then you could carry the atomizer in your handbag and use it as frequently as you want throughout the day.
Rachael’s Personal Approach to Longevity
LB: Great, thank you, Rachael for helping us walk through what that self experimentation might look like. Of course, in true Longevity Blog form Nick is already two and a half weeks into testing this on himself and will be sharing results with some very high quality Visia scanner before and after images.
As we shift this conversation toward closing out, we are really always very curious to hear how our interview guests look after their own longevity. We call it having your own longevity strategy.
Let's narrow this down into two categories. You are obviously very, very knowledgeable about the aesthetic age, looking young, staying young. What is your protocol, what things are you doing to look after your aesthetic age as an important asset in your life?
Rachael enjoys hiking and this is one of the trails she experienced recently and believes this is a one of the key factors to longevity.
RD: I think the big one because everybody looks at my skin, I have my skin routine down pat but what can throw me with my skin is hormones.
I'm almost 48 years old, I'm a woman, so hormones can be a bugbear. So really, I'm a supplement queen, I love my supplements, and most of them are adrenaline balancing and hormone balancing for me means iodine to make sure my thyroid is taken care of, vitamin B for stress levels, otherwise, those hormones really throw my skin out.
LB: And beyond aesthetics?
RD: I also try to look after my immunity and we have a couple of supplements repair for lengthening telomeres and eliminate for eliminating senolytic cells.
Another big thing, which again does come to telomeres, is I exercise. My choice of exercise is dance because it brings me joy and happiness, as well as strength and oxygen.
I think you need to find what makes you happy while also exercising so that you carry on doing it. That's a big thing for me!
LB: Absolutely, because an unhappy life is not one that you want to keep living. So I love that you take us to that point at the end. Rachael, thank you so much for joining us today on Longevity Blog.
It was really fascinating to learn about One Truth 818 and telomerase activation and all the ways that it intervenes in healthy skin. Thank you very much for joining us.
RD: My pleasure, thanks for having me!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
AKG supplement benefits your biological age? An Interview with Dr. Yelena Budovskaya of TruMe Labs
AKG Supplement benefits - A Younger YOU?
The AKG supplement has many benefits. However, the most powerful of them might just be making you biologically younger!
The AKG supplement “Alpha Keto Glutarate" has a wide array of benefits:
It improves muscle growth and athletic recovery
Delays fatigue in sport performance
Reduces muscle breakdown during exercise
Improves the health of skin by increasing collagen production
May improve bone density
Appears to improve immune function
Scavenges excess blood nitrogen and ammonia, improving detoxification
But perhaps most excitingly, recent evidence shows that it just might make you younger.
For many, this is a startling claim, so let us explain it in more detail.
First, as we will explore in our expert interview today, we can now measure biological age - meaning how old your body is, biologically (rather than just chronologically) - at home for only $100.
And second, in both animal models and in humans, AKG supplementation has been found to:
Improve the biological age of 40 humans by a median of 8+ years (clinical trial)
Change gene expression (epigenetics) to a younger state
Alter cellular signalling to be more youthful
Possibly be reducing wrinkles
May be reversing or delaying hair greying (in mice evidence is strong, in humans, anectdotal)
This is nothing short of groundbreaking information for wellness enthusiasts and longevity hackers everywhere.
If we’ve managed to catch your attention, please keep reading!
Alpha Keto Glutarate Supplement Benefits - The Why and How
Alpha Keto Glutarate is a pivotal molecule for your energy metabolism (interacts with the Krebs cycle).
The TruAge Explorer test kit. From only $100USD using the discount code ‘longevityblog’.
It is produced in your skeletal muscle and is involved in the balance of many key processes that regulate levels of carbon, ammonia and nitrogen across the body.
The reason that the AKG supplement seems to be involved with regulating aging is that the levels of Alpha Keto Glutarate decrease with age. This means that many cellular functions do not perform optimally, with many knock-on effects.
By supplementing with AKG, we may be delaying these effects significantly.
We’ve recently composed a more thorough review of AKG supplementation which you can read here.
As we move ahead, we are going to focus on the technology you can use to test whether or not AKG improves your own biological age and understand in a bit more detail why AKG supplementation might be one of the most powerful longevity interventions you can try at home.
AKG Supplementation and Biological Age - From Expert Dr Yelena Budovskaya
“AKG is actually balancing a basic metabolic process within your body, specifically the Krebs cycle...
What we see with alpha ketoglutarate is it influencing not just the methylation process, but also the methylation of certain sites associated with younger age.
Another example are the molecules called integrins that are key parts of our skin health... People do report less wrinkles and much better quality of skin.”
At Longevity Blog, we are fascinated by all things related to longevity technology. We define this sector as anything tech that is helping you stay healthier for longer.
In our post today, we are focusing on the intersection between two such technologies.
Calcium Alpha-Ketoglutarate - a longevity supplement, which we source from DoNotAge.
And, biological age testing, specifically the most affordable high quality offering on the market - the TruAge Explorer from TruMe Labs.
The unique nature and power of this combination cannot be understated. Here we have two technologies which together have been shown in clinical research, to improve the youthfulness of 40 (out of 42) human subjects.
The question is then of course - could it do the same for you?
The fantastic news is that both of these technologies are available to you in the safety and comfort of your own home.
With a bit of careful forethought, you can run your own self-experiment to see if AKG can improve your biological age for only a few hundred dollars (with our unique discount codes).
To understand how this all works in more detail, we reached out to CEO and Co-Founder of TrueMe Labs, Dr Yelena Budovskaya to learn about how biological age testing works and why Alpha Keto Glutarate appears to be so powerful for maintaining your health as you age.
Let’s hear what she has to say…
NOVEMBER 2023 UPDATE:
Nick has now completed his 9 month self-experiment with Ca-AKG. Read the results here!
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with TruMe Labs, we have a negotiated an industry leading 15% off coupon code for our readers.
Use the code “LONGVITYBLOG” at CHECKOUT TO SAVE 15%!
And through continued collaboration with DoNotAge, we are offering a 10% off discount for their Calcium Alpha-Keto Glurate supplement as well!
Use the code “Longevityblog” at checkout to save 10% on AKG
This interview was conducted in November 2022 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Alpha Keto-Glutarte, biological age & More
Longevity Blog (LB):
Yelena, thank you so much for joining us today, we're really excited to talk with you about biological age testing. You've co-founded TruMe Labs and you offer the TruAge Explorer test kit.
We might hear about biological age testing all of the time, but it's still a new concept to most people. And it's fundamental for the rest of this discussion.
An important important place to start: how do we determine biological age?
Yelena Budovskaya (YB): Biological age is the age an individual would be if they lived a perfectly healthy life, and did not take any anti aging supplements. His physiology will be representative of that generic age group. Your biological age is the physiological state of your body, not the years by calendar.
Interview excerpt: Biological age testing - how it works, what it means (in three minutes)
Biological age - How young you are on the inside
“Your true biological age... might be a little bit behind... or it might be faster than your chronological age. But in any case, it is more representative of your health...”
LB: In that way, we're looking at an age that tells you what you “look like” biologically, not necessarily what the clock says. But instead, comparing you to other people than other populations saying, do you look older or younger at a cellular level?
What would you add to that?
YB: We look at how your cells and in particular how your DNA looks after all you put it through over the years. How that information is written on your DNA is reflecting your physiological state.
This physiological state is your true biological age. So it might be a little bit behind your chronological age. It might be faster than your chronological age. But in any case, it's more representative of your health rather than your calendar years.
Biological Age Reveals How Old You Really Are - for ONLY $100USD
Nick with an AKG supplement from DoNotAge
LB: So ‘biological age’ is comparing your biology with other healthy individuals in your age group to see how you stack up in terms of biological years accumulated or not accumulated.
In this space, we've had biological age testing for a few years now, but they've traditionally been quite expensive, costing $400-$500 US dollars per kit. One of the most attractive aspects of the TruAge Explorer biological age test kit is that it's very affordable.
Talk to us about the innovations that are occurring at TruMe Labs in terms of biological age testing. How can you offer a biological age kit for only $100 US dollars?
Speaking of supplements - Our Founder Nick tried the supplement Nicotinamide Mononucleotide and measured biological age before and after. Curious? So were we… read the post!
YB: Our journey actually started quite a while ago. I spent so many years studying the natural genetics of the aging process.
One of the things that I noticed is that we cannot stop human beings from aging. But nor can we stop them from trying to extend their lifespan - people are always going to be searching for the answer to their aging process.
With the expansion of internet and social media what's happened is more individuals are reading new innovative science in longevity and they think “Okay, I'm gonna start taking that supplement tomorrow. If it works on mice, it should work on me”.
When I first started in this field, it shocked me to see a lot of people who take a lot of supplements without really checking whether or not it's actually working for them.
self-experiments & biological age tests
LB: It is so refreshing to hear you say this. Part of our philosophy at Longevity Blog is to guide people to know the answer to what works for them! Go on.
“When I first started in this field, it shocked me to see a lot of people who take a lot of supplements without really checking whether or not it’s actually working for them. ”
YB: Then we start thinking - how can we measure if these interventions works? And of course that means we needed a biomarker of aging. Today, we know many companies are spending the time looking at biomarkers of aging.
I really liked what Steve Horvath, Hanham and other centers in genetics were doing, because it looks like that biomarker was actually very simple to adapt to home testing.
LB: This is referring directly to epigenetic biological age clocks, based on DNA methylation data.
YB: Yes, but DNA methylation is a very dynamic process. We started the development of our test kit with several basic requirements in mind.
Firstly, how can we make our test very accurate. So deviation from the number that we predict, should not be more than five years.
Second, it should be affordable - no more than $120. About the cost of three months worth of vitamins.
Feeling impatient and just want to learn about Alpha Keto-GluTArate and biological age? Just Scroll down a few sections!
Third, it should be fast, because the tests that we've previously done take 8 to 10 weeks to complete. We wanted to have a two week turnaround time. And no needles!
LB: That’s a great answer, we can see that affordability was actually just one part of your holistic thinking about how you might produce a quality and low cost kit.
Does the AKG supplement actually work? What about other longevity supplements?
We love the part of the story where you referred to how others were taking supplements without knowing if the are actually working for them. This is precisely one of the things we talk about on Longevity Blog, repeatedly.
In your answer you mentioned accuracy - we want to get into some of the details around the accuracy and precision of your test. But first, we’ve just introduced the concept of “epigenetic” age testing where the test is looking at the epigenome and particularly these sites called CpG islands.
These locations control turning the genetic code on or off in our bodies. Please briefly tell our audience a bit about that process of on/off in the epigenome.
If you want to go deeper on biological age clocks, epigenetic aging and what all of these terms mean, check out our interview with Ryan Lewis, Founder at TruDiagnostic.
YB: Even at birth, we already have some level of methylation happening in the body. And as you mentioned, this is the CpG sites on our genome. These CpG sites are located all throughout genome.
In some cases they are in the “promoter region” of the gene. Methylation at these locations prevents the cellular machinery from binding this region before the gene and expressing it.
In some way, epigenetics is a dynamic mechanism instructing the cell to turn on and off genes to fine tune how the genes are working together.
DNA Methylation and Biological Aging
LB: Why is this turning on/off of genes important for aging/longevity?
You don’t have to use supplements to improve your biological age. Nick did it by adding more plants to his diet, read about it here.
YB: DNA methylation is happening all the time. DNA is methylated and demethylated. Certain genes activate expression and other genes repress the expression.
This is how the body is fine tuning its function throughout life. It can be associated with the biomarkers for almost every single physiological process with the body.
LB: With aging, tracking this process is incredibly complex. Some of the other technologies we looked at for biological age testing might look at hundreds of thousands to millions of points in the epigenome.
However, your biological age test kit has actually boiled it down to looking at just nine locations in the epigenome. Clearly those are very closely related to aging.
Can you help our readers understand how there could be this reduction from millions of points in the epigenome in some of the fancier, more expensive test kits down to just nine points in your TruAge Explorer test?
Low Cost Biological Age Testing: How TruMe Labs Made it Happen
Test your biological age for $100USD with TruMe Labs and our discount code “longevityblog”
YB: When we first studied epigenetic connections to aging, we looked at the whole genome, because we didn't know much. We didn't know where this information was actually kept.
Any model that uses epigenetics to calculate biological age is a statistical mathematical model. It converts DNA methylation data into the number that corresponds to the biological age.
As we have studied this more we have realised that not all the biomarkers are the same. Some of them actually influence and can predict your biological age more. Most others have a miniscule influence on the equation.
We have identified the methylation markers that change with age, which are promoters of those genes. These markers should also be age regulated (changing its expression with age).
When we put these constraints over our algorithm development, we end up only with 30 CpG sites. But still, 30 was too many sites for the affordability and scalability of the process that we were developing.
So we distilled it to the best performers (9 of them). Afters some early testing and improvements, we validated it within a clinical trial setting and we saw that our deviation from the chronological age of the healthy individual was only 3.8 years, which met our accuracy target.
How does TruAge Explorer Compare to More Expensive Biological Age Tests?
LB: What an interesting story to follow. You've described this process of thinking about how to constrain a very complicated problem through the lens of affordability and the very dynamic relationship between gene expression and aging.
You’ve mentioned accuracy again, so let’s discuss this in more detail. You've done a comparison with your kit to the MyDNAge test. That test kit uses a much larger portion of the epigenome (approximately two thousand CpG data points). And yet there's a really strong correlation between the outputs from your algorithm and theirs.
Tell us what that reveals about these nine CpG sites and the way you've just constructed the test?
YB: Well, of course I think it tells you that we're probably found the CpG sites that are more dynamically changing with age and that methylation within those sites is clearly important for measuring a normal natural aging process.
The main reason our accuracy is comparable to another test in the market is because we are actually using different technology.
We don't use next generation sequencing (NGS), because we wanted to keep the cost down. NGS is quite expensive unless you sequence hundreds of patient samples at the same time.
We are instead using single sequencing, which allows us to sequence at a greater depth. In other words we sequence the same region many, many, many times over.
Low Cost Biological Age Test, the Makings Of
LB: Let's help our readers understand in a bit more detail. Just so it's nice and clear.
You've described Next Generation Sequencing, which enables many samples to be computed in parallel. However this is not the route that you've chosen, as you’ve pursued affordability. Explain to us again, what the difference in your single sequencing approach means for the consumer.
YB: What we do is sequence only one sample at a time. From this one sample, one fragment at a time.
Altering CpG sites in action. By sleeping better, Stacey improved her biological age from TruMe Labs. Read their female biohacking guide here!
Let's say we are sequencing nine fragments, the nine CpG sites. This means we sequence each of the CpG sites separately.
For each of the sites, we look separately at all the messages we get to calculate the percentage of methylation at that particular site.
This means we get thousands to tens of thousands of messages that we aggregate together to calculate the percentage over one CpG site.
As a result, we can use statistics over these many messages to see how clean the sample was.
There's one positive side and one negative side of this approach. The positive side is, because we sequence it so deeply, it means that we can actually capture miniscule changes of methylation, which can have acute effects on your biological age.
The negative part is that our test is much more sensitive to your lifestyle changes than tests using the NGS approach.
Is the TruMe Age Explorer Precise? Repeatable results are key for self-experimentation
LB: Both the price point and the sensitivity to lifestyle changes make the TruAge Explorer a very nice tool for self experimentation.
Read our interview with Ryan Smith at TruDiagnostic to understand the importance of accuracy and precision for biological age testing.
Let's talk a little bit about error and precision in the test kit. We recently discussed these concepts with Ryan Smith of TruDiagnostic. Talk about your test through the lens of accuracy and precision.
YB: Yeah, so we actually tested two aspects of precision and accuracy.
The first was precision. Let's say, I give you five tests today and you collect your saliva across five samples. So the sample is the same, right? It was put in the paper at the same time, and was sent to us in the same envelope. So what is the result is going to be?
We actually tested this quite a bit and the result is that we predict biological age from these five samples to within 3 to 4 months of each other.
Then a second aspect of this is actually a bit tricky but super important to understand. And I'm not sure very many people actually understand it.
LB: Our audience will! Give it to us.
YB: Every single biological age algorithm, including ours, uses the chronological age to standardize your biological age number. This presents an issue - why is the chronological age the standard?
Well, we don't have any other markers right now that reliably would predict that. So that's why we still use it. And this is why I keep bringing up this healthy individual who does not take any anti-aging therapies, who would live a healthy life and overall being healthy in perfect health today. What is their biological age?
We make the assumption that their biological age is equal to their current chronological age.
Then we took individuals between ages 40 to 75 that were absolutely healthy. No chronic diseases, no big problems. When measured the biological age of these individuals (150 of them) we realised that were within plus or minus 3.8 years of that person's chronological age.
This is why we know that even with multiple repeats of the same test, we can say that we can predict person chronological age plus minus 3.8 years.
“We get biological age as a starting point, do something to change the biological age and then compare follow-up results to your first biological age test.
The goal is to make that number smaller (“younger”).”
TruMe AGe Explorer: Precise to within 3 months, accurate to within 4 years
LB: This is a really fascinating point that you're making. We are going to try to say it back to you in different terms.
You're saying here is that to know how “accurate” a biological age test result, we have to find a compare that to a source of truth. When we consider “what is the right answer?” or what is the “true age” of a given person, TrueMe Labs construct this by looking at both the biological age and chronological age of many healthy individuals across different ages, statistically.
Here, you found an accuracy of plus or minus 3.8 years.
YB: Exactly. But I want to add to that.
If you personally are taking a biological age test, the most important thing is actually comparing your own results after an intervention. We get biological age as a starting point, do something to change the biological age and then compare follow-up results to your first biological age test.
The goal is to make that number smaller (“younger”).
AKG Supplement BenefitS Video: Reducing Biological Age
AKG supplement benefits for biological age with Dr Yelena Budovskaya of TruMe Labs.
LB: This is great, because you're coming back around to the concept of self experimentation.
We believe this is true value of biological age tests. They are giving you a reference point from which to improve.
This is why it's so important to pick a kit that you can afford that you have confidence in, and to keep using it. Because you get your baseline result and then try to improve and see what works for you.
We have a really great example in the literature of this - your company the TruMe Labs technology worked participated in a clinical study published in the journal Aging back in 2021.
November 2023 Update: Nick’s 9 month self-experiment with Ca-AKG results are in! See how much his biological age improved.
There were 42 participants self-experimenting with an alpha ketoglutarate supplement (AKG), which we've just recently written about on the blog. Your TruMe Explorer test kit had an important role in that study.
Can you tell us about this study?
YB: This study was done in collaboration with Ponce de Leon Health, who are producing the akg supplement. They wanted to give their clients the opportunity to be sure that their product works.
In this study, the result showed that so many of the participants actually decreased their biological age significantly. They also reported that they don’t have gray hair anymore and that their skin health improved.
We saw that on average there was 8.8 years of healthy lifespan reversal. Only two people actually did not improve their biological age.
AKG Supplement Benefits: Why it Works on Biological Age
LB: We love this. We think this is the longevity science of the future, particularly as longevity technologies move faster and faster.
This is why finding a kit that we can use for self experimentation is so important.
Score a 10% discount of high quality, third party tested Alpha Ketoglutarate from DoNotAge.
How do you think the alpha ketoglutarate supplement is working on these nine CPG sites in a way that improves biological age? What’s happening here?
YB: I think the AKG supplement is actually balancing a basic metabolic process within your body, specifically the Krebs cycle. AKG is also important for increasing the activity of demethylase, which is the enzyme that the methylate the genome.
What we see with alpha ketoglutarate is it influencing not just the methylation process, but also the methylation of certain sites associated with younger age.
Another example are the molecules called integrins that are key parts of our skin health. They are important for wound repair and skin elasticity. We observed that some of those markers actually methylated more with alpha ketoglutarate.
Maybe that's why there's such a great effect on skin. People do report less wrinkles and much better quality of skin.
The Future of Biological Age Testing
LB: Thank you for diving into that. Our audience loves looking after their skin health!
As we move to close the interview, can you share us your your vision for biological age testing? Where is it going over the next five years? What will become possible?
YB: We think that the most important thing right now is not actually making more precise biological age measurements.
Instead, we intend to expand our portfolio with genetic tests which give you information is how your DNA by drivers of aging. For example, how you are are affected by your diet taken or by the air you breathe, or your stress levels, or level of inflammation in your body. This could also included your hormone status.
We are going to be combining epigenetic and genetic tests together to deliver this information. So this is where we're heading next.
Dr Yelena Budovskaya’s Longevity Strategy
“I also finally tested alpha ketoglutarate on myself. It actually did work and I love it! ”
LB: That's an exciting vision. We love that you have this idea of combining different types of data in practical way for people to influence their longevity, at ho
We're going to wrap up the interview here. But before we go, we'd like to ask every guest to just share one or two things that they do to look out for their longevity each day.
Hear from our Founder Nick on biological age testing and how you can change diet, sleep, exercise and stress to improve yours! Read more
YB: Personally, I have always been fighting with weight loss. I was also guilty of taking too many supplements.
Now I practice intermittent fasting and am trying to get my feeding window to just six hours a day. It seems to work great for me. I like the effect this is having on my body.
I also finally tested alpha ketoglutarate on myself. It actually did work and I love it!
Everything else I am trying, I aim to be very thoughtful and self-experimenting with one intervention at a time.
LB: Thank you for your answer Yelena, and thank you again for joining us on Longevity Blog today. It was a pleasure.
YB: Thank you. I'm looking forward to see what result you get from your AKG self-experiment!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
One Year With OneSkin OS-01 - Review, Questions and Where to Start
we have updated our oneskin OS-o1 Review
Curious to know if OneSkin OS-01 actually works?
At Longevity Blog, looking younger is about far more than vanity. How ‘young’ you look is an asset to be protected, an investment in your longevity, particularly in developing and maintaining a longevity mindset.
But as we have previously explored, keeping your skin young and healthy extends into actual, tangible longevity benefits much beyond aesthetics and how young you ‘feel’. By switching on the repair mechanisms of your skin, you are reducing systemic inflammation across the body. In doing so, you’re slowing down ‘inflammaging’, one of the key reasons you get biologically older in the first place
In our interview with OneSkin CEO and Co-Founder Dr. Carolina Reis, we heard about the destructive role of senescent cells in the skin. These aged cells send off inflammatory signals to the surrounding tissue, which extend their impact throughout the body.
But, by looking after the healthspan of the skin - “skinspan” as OneSkin refers to is - we can halt or even reverse this process.
“Once you have senescent cells, there is a cascade of inflammatory signals leading to events such as collagen breakdown, which in turn will lead to a series of further dysfunctions in the skin.
These results in breaks in the skin barrier, and eventually, the signs of aging that we experience growing older, which are loss of firmness, wrinkles, dark spots, and so on.
If we're able to partially block the senescent cell feed forward loop, this allows the young and healthy cells to continue to proliferate, keeping up with healthy collagen and repairing your skin barrier, essentially reversing aging.” (Dr. Carolina Reis in our interview with her from February 2022)
But does oneskin actually work?
A classy, sustainable and innovative product. OneSkin OS-01 FACE.
It’s one thing to claim you can reverse skin aging, another to suggest you can halt or reverse cellular senescence in the skin.
It is another matter altogether to prove it. To know - “Does OneSkin OS-01 actually work?”
At Longevity Blog, our job is to put such claims to the test. And we did this, in a groundbreaking self-experiment that we published in August 2022 after our Founder Nick tested their product on his face for six months.
The results were impressive. With a reduction in Nick’s apparent skin age (as measured by a Visia scanner) of 7 years. (See the Before and After review here)
ONeSKin OS-01 - ONe year Later
In this brief follow-up, we wanted to share Nick’s further experience with OneSkin OS-01 after 12 months of using this product.
It’s natural to wonder, what happens after longer term use of OneSkin? Or was the testing a fluke? Could another factor have been in play?
Over the course of the 12 month period, Nick did not make any major changes to his skincare routine. He maintained regular sunscreen use and daily cleaning with a squalene cleanser. He applied a generous amount of OneSkin OS-01 FACE each evening, and watched the results come in.
As Nick is now executing a follow-up self-experiment with IPL Laser Therapy (be sure to subscribe to get notified when we drop this exciting new video project!), it was time to gather some additional Visa scanner data.
What he found might surprise you….
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with OneSkin, we have a negotiated a 15% off coupon code for our readers.
Use the code longevityblog at checkout to save!
Note: You must use the above link for the discount code to be applied to your order.
OneSkin OS-01 FACE, after 12 months of continual use at once per day, significantly improves skin texture.
OS-01 FACE Smooths Skin Texture Dramatically
Texture as measured by the Visia Scanner is primarily an analysis of skin smoothness. Texture measures skin color and smoothness by identifying gradations in color from the surrounding skin tone, as well as peaks (yellow) and valleys (blue) on the skin surface that indicate variations in the surface texture.
While Nick’s forehead was not sampled in the before image, his cheeks were in both the before and after. We can see a dramatic decrease in the peaks and valleys from left to right.
Anecdotally, Nick’s skin ‘feeling smoother’ was on of the most notable benefits of using OneSkin.
OneSkin OS-01 FACE, after on year of daily use, appears to reverse Nick’s wrinkles.
ONESKIN reverses wrinkles
While we saw a significant decrease in wrinkles after six months, those changes were only just beginning. After 12 months, we can see the Visia scanner barely detects wrinkles on Nick’s face.
“Wrinkles” are furrows, folds or creases in the skin. These are known to increase in occurrence as a result of sun exposure, and are associated with decreasing skin elasticity.
“Once you have senescence cells, there is a cascade of inflammatory signals leading to events such as collagen breakdown, which in turn will lead to a series of further dysfunctions in the skin.
These results in breaks in the skin barrier, and eventually, the signs of aging that we experience growing older, which are loss of firmness, wrinkles, dark spots” -Dr Carolina Reis, OneSkin CEO- (read the interview)
OneSkin OS-01 FACE using it for one year seemingly halts the accumulation of new UV damage.
OS-01 Peptide holds UV damage stable
While we didn’t see any big changes in Nick’s UV damage levels over the 12 months, this means more than you might think.
UV damage is accumulating due to sun exposure over the course of your life. As a triathlete, Nick is outside often and gets plenty of sun exposure. Australia, where Nick lives, is also known for very high UV levels and high incidence of skin cancers.
You can learn about technologies for detecting skin cancers early in our interview with MoleMap.
The analytics on the Visia Scanner showed a small, but meaningful decrease in ‘feature count’ - otherwise tracking the total number of UV spots underneath his skin.
With this small decrease and UV damage overall holding stable, even with Nick getting chronologically ‘older’ - it does look like OneSkin OS-01 is helping out in this category too, although less dramatically.
OneSkin OS-01 FACE, used for 12 months with no other changes, significantly improves spotting (skin lesions, pigmentation).
ONESKIN OS-01 FACE reduces spotting
“Spots” as detected by the Visia Scanner are typically brown or red skin lesions including freckles, acne scars, hyper-pigmentation and vascular lesions.
Spots are distinguishable by their distinct color and contrast from the background skin tone. Spots vary in size and generally have a circular shape.
After one year with OneSkin, Nick’s spotting dropped by an impressive 40%!
ONESKIN after one year - We’ll keep Using it!
Our verdict continues to be that OneSkin OS-01 not only works, but is an essential part of your longevity strategy for your skinspan.
In world awash in ‘beauty’ products and ‘skincare’ brands, we are proud to be collaborating with a longevity technology company like OneSkin who are breaking the mould and targeting skin aging at its source.
However, these results really only apply to one person - that’s our Founder Nick. If you want to know if OneSkin OS-01 will work for you - there’s only one way to find out!
Run your own self-experiment! We provide some good tips on how to do just that in our previous blog post here.
If you decide to give OneSkin a try, be sure to use our exclusive discount code to save 15% and extend your longevity budget just a bit further.
Enter ‘LONGEVITYBLOG’ at checkout. Note that you must use our unique link here to have this code applied to your order.
If you do self-experiment, we’d love to hear from you! Please share your results with us and who knows, you might just end up on Longevity Blog yourself!
The First Longevity Blog Video Project is Here - IPL Laser Therapy
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
How Fast are You Aging? A Biological Age Test for Rate of Ageing with Ryan Smith of Trudiagnostic (Part 2)
How Fast are You Aging?
Are you considering taking a biological age test?
If so, you probably are interested to know - how old am I really?
When investing in a biological age test kit, you’ll want to choose the product which has the best accuracy and precision. What does this mean? We’ll discuss this in detail in today’s interview.
This is of course a tempting data point for those interested in their longevity. But any given biological age test is really only a snapshot in time.
We often argue that the real value in biological age tests is in their ability to test, undertake a longevity self-experiment and re-test to see if your bio age improves. See this example or this example to see what we mean in more detail.
Using test kits in this way mean you really have to purchase at least two biological age tests. Even with the lowest cost kits, this means spending at least $300-$400USD.
However, recent developments in this space mean you can now see your rate of aging in a single test. This arguably saves you on cost twice - as the rate of aging biological age test kit is about half the price of the full test and you only need to purchase one kit.
TrueAGE PACE TEST KIT REVIEW
The capability to directly measure rate of aging has been developed by Longevity Blog partner TruDiagnostic. To our knowledge it is the only biological age test kit with this capability (at the time of writing).
This test (TruAge PACE) analyses short-term changes in epigenetic methylation and is a sort of “speedometer for aging”. Those looking out for their longevity want this speedometer value to be as low as possible!
This kit has very high precision and is very responsive to interventions, whereas most epigenetic test kits giving you a biological age are slow to respond. The TruAge Pace test kit is arguably quite ideal to see which longevity technologies are working for you.
Of course, we’ll be working to prove that hypothesis (be sure to subscribe to monthly updates to hear the answer!)
It is worth noting that the full cost kit from TruDiagnostic - TruAge Complete includes the rate of aging result (as well as extrinsic age, immune age and telomere age + more).
How Does Rate of Aging Testing Work?
To get into the details behind how the TruAge Pace test kit works, we continue our interview series with Ryan Smith the Co-Founder and VP of Business Development at TruDiagnostic.
We recently interviewed Ryan, and in the first part of this series, we had him walk us through the recent developments in biological age test kit technology.
One of the most important take-aways is that you want to be choosing a third generation biological age clock to get the most accurate and precise result. Be sure to review it for more details!
Today, we’re exploring this concept of the rate of aging and looking into Ryan’s view of the longevity technology roadmap - where will biological age test kits go next?
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with TruDiagnostic, we have a negotiated a 12% off coupon code for our readers.
Use the code longevityblog at checkout to save!
This interview was conducted in August 2022 over Zoom and is an audio transcript with edits for clarity, brevity and correctness.
How fast are you aging?
Ryan Smith, Vice President of Business Development at TruDiagnostic is an expert in the latest developments in biological age testing.
Longevity Blog (LB):
TruDiagnostic are also providing an estimate of how fast you are aging. This is unique, and part of the reason this is possible is due to the DunedinPACE algorithm being a third generation clock.
Can you give us a brief history of why the city of Dunedin has become important in building a unique biological age algorithm?
Ryan Smith (RS):
This data comes from a study started in 1972, with a group of right around 1037 New Zealand children all at the age of three. They started this cohort by tracking them all the way across their aging process.
Now we're here, we are in 2022, and these individuals are approximately 50 years of age with 900 or so of those patients providing us information and blood biomarkers showing us how they're aging throughout their life.
Dunedin is located on the South Island of New Zealand. The Dunedin Study has followed the lives of 1037 babies born in 1972/73 since birth.
The study is now in its fifth decade and has produced a considerable amount of data that shapes what we know about the rate at which humans age.
This is a very, very unique cohort that really doesn't have replication anywhere else in the world.
LB: Do we have epigenetic measurements from these folks?
RS: Thankfully, they have saved some of that blood, but unfortunately, we haven't had epigenetic measurements across the entire lifespan.
It would be great if we did, but we have taken a lot of other lab measurements across their lifetime. And those 19 blood related biomarkers are what we have used to train an algorithm to estimate the pace of aging.
Following Individuals Aging over Time = Rate of Aging Algorithm
LB: So there's the connection from the blood based biomarkers to the rate of aging and methylation data. And all gathered longitudinally, again, which is what makes the third generation clock so powerful.
Let’s come back around to DunedinPACE’s (the algorithm behind the TruAge PACE test kit) ability to estimate the rate of aging. Explain how this works.
Source: TruDiagnostic ‘Pace of Aging’ report document.
RS: In order to look at the rate of aging, you have to have some context for the change over time.
What we do is look at all those 19 blood related biomarkers and giving them a composite score. Then looking at how that score changes as these individuals age from the time they were 3 years old to now, we can see what is optimal.
We really get to see what is happening on average to most people as they age chronologically with very little intervention. This gives us a standard to see - what is the average pace of aging?
We can show our customers how they individually compare to that, where we can get an instantaneous point in time measurement of what their aging rate is at this moment.
I think this is very exciting because most other clocks are encompassing the entire body's aging process over the course of a long period of time. But these instantaneous markers are showing how you are aging right at this moment.
This can be very helpful in terms of finding out what lifestyle changes or interventions are working on an individualised basis.
How to Improve Your Biological Age Rate
“We also know TruPace has probably the most accurate or most predictive of all clocks... this rate of aging estimate is responsive instantaneously”
LB: That last part that you just mentioned, in terms of determining what works on an individualised basis, is right at the heart of what we like to do at Longevity Blog.
One thing we find really fascinating about the TruDiagnostic TruAge test kit is this rate of aging algorithm.
We suspect it will actually be more responsive to interventions and helping our readers self-experiment and see how the rate of aging is changing.
The extrinsic age is a pretty sticky number. It's harder to change and takes longer. Do you agree with our thinking? That the rate of aging estimate lends itself better to the everyday longevity enthusiast or biohacker?
RS: I certainly think it does, and I think that we've already talked about some of the reasons why.
One is precision. This clock is extremely precise. That means as you're measuring biological age more frequently, you want an even more precise clock.
We also know it's probably the most accurate or most predictive of all clocks. Ultimately, this (rate of aging estimate) is responsive and responsive instantaneously.
Sometimes it can be very hard to improve or to fix damage. We know this to be true when dealing with classical aging, where it's harder to reverse disease than it is to prevent it. With some of these biological age clocks, what you're measuring is the whole history of a person being alive.
“With some of these biological age clocks, what you’re measuring is the whole history of a person being alive”
With the rate of aging estimated, you're getting a more intermediate effect. And that intermediate effect is absolutely correlated to health outcomes.
So as someone who is trying any type of intervention, whether it be diet, nutrition and exercise, they can look at their rate of aging and then find out what is the most optimal strategy for them by comparing markers even within three months.
LB: That's really valuable for the self experimenter.
TruDiagnostic Biological Age Test Kit Includes Telomere Age
Extract of the TruAge Complete telomere based biological age estimate.
LB: So far we’ve discussed three biological age values. Extrinsic, intrinsic and rate of aging. We won't talk about today, but we’d like to also mention that there's also a telomere based estimate that TruDiagnostic offers through the TruAge Complete test kit.
A theme has been building through this conversation about third generation biological age clocks. One innovative area of development for such clocks is a new and very powerful capability to be predictive of specific disease outcomes.
Tell us briefly about how TruDiagnostic test kitsare starting to connect the dots to certain disease risks.
Biological Age and Age Related Disease Risk
RS: We're lucky enough to have biobanks that have taken samples from 30 years ago. This enables us to look at how their epigenetic methylation correlated to the health outcomes that they faced.
A good example is our validation with the Framingham Heart Study cohort. We found that those people who are aging anywhere below one year per year generally would have a 50 to 50% less chance of dying over the next seven years. They also have a 54% decrease risk of a chronic disease over the next seven years.
But those people with an aging rate above one year per year, so called ‘fast agers’ were overall 65% more likely to die. That's obviously just talking about mortality.
“People who are aging anywhere below one year per year generally would have a 50 to 50% less chance of dying over the next seven years”
We have also found that the rate of aging marker is predictive of things like grip strength and muscle mass, as well as IQ and mental processing speeds, and even facial aging.
We have some really great composite images of how people age in our cohort, grouped according to their rate of aging, and even at age 45, the 10 slowest aging members of the cohort look to be maybe 20 years younger than the same individuals at 45 with a fast aging.
The Future of Biological Age Testing
LB: We love to talk about tools for disease risk on Longevity Blog. We believe there is significant value in thinking ahead about your personal risk, and that by analyzing that risk profile you can get 10 to 20 years ahead of the age-related problems you're going to develop.
As your team looks forward, what is going to become possible for TrueDiagnostic in the near future? Your company is actually very fast moving - you're putting out new reports every few months - tell us one or two new and exciting capabilities that are coming in the next year.
RS: There are a couple of things that I'm really excited about.
TruDiagnostic can analyse your epigenome to reveal much more than just your biological age. They are adding new reports regularly, including a recent ‘weight loss’ report to better understand how your body might respond to calorie restriction, for example.
One of which is a project we've been working on for a long time - what we consider a fourth generation algorithm. In order to do this, we want to include what we call multiple levels of the “multi-ome”.
This is a very complex process. We already have talked about how challenging working with longitudinal data can be, and how it is really important to remove confounding factors. But if we can also add to that longitudinal score more depth on those physiologic measurements or those molecular measurements, then we can get an even clearer composite image.
We are in collaboration with Harvard and have been working on a multi-omic clock for probably two years, now. It will include genetic data and will include some micro RNA data, as well as epigenetic, proteomic data (peptides and proteins in the blood), and then lastly, metabolomic data (metabolites in the blood). We will also expand it to to include 75 blood related biomarkers (up from 19 in the current version).
Measurement will take place over four different time points, which should allow for a biological age clock that is hopefully unparalleled, in terms of its accuracy and precision. So we're really excited about that.
LB: I think it is a very exciting version of the future capability of biological age clocks.
Ryan Smith Co-Founder at TruDiagnostic’s Longevity Strategy
Wrapping up our interview, one thing we always ask our guests is this - knowing all the developments upcoming in longevity technology, what are you doing everyday to look out for your own health and longevity? Tell us part of your longevity strategy.
RS: One thing I'm ashamed to admit now is that previously, I was, I would say, a big skeptic of the importance of meditation and mindfulness. I used to think, you know, am I doing this right? Is this really meditation? Is this even working?
Stress has a “Major Impact” on Biological Aging
The impact of stress and emotional regulation on aging and the aging process is incredibly strong. It is way stronger than I would have ever anticipated. It still baffles me that someone's emotional regulation can have such a major impact on their biological aging process.
Stress, sleep, diet, exercise - these all impact biological age results. Want to learn more? Check out our interview with Dr Robert Lufkin on YouTube here.
We're still not really sure how this is mitigated. I think a lot of people might say it's regulated by cortisol or some of these other stress hormones. But I can tell you that it has a major impact. And so one of the things I really try and do is to spend some time on mental health. I was never that way previously. But you know, seeing the results I've seen and the correlations I've seen, I've definitely done a 180.
In addition to that, from an interventional approach, I tend to be a very big fan of rapamycin and mTOR inhibitors. In all the aging interventions that we know about now, this one is probably one of the most exciting for wide scale application.
Lastly, even though I am probably not the best at actually implementing this into my own life, I think periods of fasting, fasting and caloric restriction are also some great strategies which have very little downside and have the potential to have really good longevity benefits.
LB: As that's fantastic, Ryan, we're going end the interview there. Thanks so much today. We really appreciate your time.
RS: Thanks for having me as guest on Longevity Blog!
Trudiagnostic Discount Code!
A part of our mission is to make your longevity budget stretch further.
You can save 12% off TruAge Complete or TruAge PACE biological age test kits.
se the code longevityblog at checkout and save!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
At Home Laser Treatment for Arthritis and Joint Pain with the Kineon Move+
Reducing joint pain and inflammation with laser therapy
New things are possible for your joint health, as the next generation of ‘at home’ light therapy devices hits the market.
Could the Move+ from Kineon heal your knee/joint pain? Yes, it certainly could. Read on for more…
Laser therapy for chronic joint pain - does it work?
The answer hasn’t always been yes. Amazon and eBay are awash with low quality imitators and ‘cold laser’ clinics have popped up around the globe with very mixed reviews.
We’ll spare you too many details, as we know you’re in search of something that actually works (hang tight - we won’t disappoint!)
In short - there are many pitfalls facing new users of laser therapy devices.
Three Issues with At Home Laser Treatment Devices
Firstly, most at home treatment options claiming to be ‘lasers’ (watch out for 'low level’ or ‘low intensity’ or ‘cold’ terminology) are simply using LEDs and are not truly a laser therapy device. One ‘tell’ is that light power will be rated in the milliwatts (mW) rather than watts. These devices will never get light deep into your joint (necessary for stimulating stem cell activity and oxygenating blood!).
Secondly, nearly all of the lower cost devices are not effectively calibrated to penetrate joint tissues at depth. This is related to the first point (power), but there’s more to consider - light needs to be focused in a column not a spray to penetrate into the joint. LEDs cannot do this - you need an authentic laser emitter (with true light amplification).
Third, price point. We’ve reviewed all of the at home laser treatment devices we could find. Most of them do not have enough power, nor do they focus light in a column appropriately. The few that do cost several thousand to tens of thousands of dollars. This is why the laser treatment options that actually work have historically only been used on athletes or available at expensive clinics.
Choosing Effective At Home Laser Therapy for Joint Pain and Arthritis
These three issues do not mean that at home laser treatment for joint pain is a bust! They simply mean that you need assistance in choosing an at home laser therapy for arthritis pain - and that is why the team at Longevity Blog have done the hard work for you!
The aches and pains of arthritis and joint pain in general are usually driven by one key factor - inflammation.
We review the basics on how to keep your cartilage healthy and your joints pain free in part one of our interview series with Kineon.
We highly recommend you check it out!
We are always tracking the latest developments in longevity technology (which is why you should subscribe to our monthly updates!).
A key trend we discovered in this process is that the proliferation of laser devices in aircraft, cars, robotics means the price point for high quality lasers has recently begun to fall very quickly.
Kineon, led by pioneering CEO Forrest Smith, were very quick to realise the opportunity to bring low cost, high quality laser treatment for joint pain to the market. With the Move+ launching just months ago, we knew we’d found a game changing device for at home treatment of joint pain. They have cracked the trifecta of problems in laser quality, device calibration and price point.
And as their devices have begun shipping to users worldwide, self-experimenters everywhere are validating the effectiveness of this device. Today, we’re going to discuss how you can get your hands on one and hear from Forrest directly on how to self-experiment at home to know if laser treatment for joint pain will work for you.
Kineon’s Move+ - a light therapy device which relieves joint pain safely and quickly by stimulating factors which support healthy joint cartilage.
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with Kineon, we are please to offer a 10% off coupon code for the Move+, exclusive to our readership
Use the code “longevitymove+“
This interview was conducted in June 2022 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Be Sure to Read Part One of the Interview with Kineon Here!
Laser Treatment for Arthritis in Hands, Knees, Joints
Longevity Blog (LB):
Coming back to the beta testers you mentioned - using the Move+ on yourself and testing how it might work for you is what this audience loves to do. It's one of the things that we focus on.
Often our Founder Nick is the guinea pig, but increasingly our audience are participating and sharing the results with us.
The Move+ seems to offer great opportunities for self experimentation. Let’s consider a reader who has, say, a shoulder or a knee issue and is interested to try the Move+
Let's talk about how they would do a self-experiment. Let’s hear some details - how long they should run it for, how often they should treat the joint and what they could effectively measure before and after?
Self-Experimenting with the Kineon Move+ for Joint Pain
Forrest Smith (FS): We've run a number of different tests and found a couple that are really interesting. I’ll share the most accessible one.
One way to check if the device is working through all of the mechanisms that we've discussed is using a blood flow restriction cuff where you can reduce the blood flow to the affected limb to essentially zero. Then, you remove the cuff and let the blood reperfuse.
You measure how long this takes, first recording a baseline measurement. Then you test again after several weeks of treatment. This is an extremely powerful test in a couple of ways.
One - the faster your tissue reperfuses, the healthier you are from a cardiovascular standpoint. Second - in most instances, any previous injury (such as an old ACL tear) will result in slower reperfusion of the blood into the affected leg.
You should be able to see a difference after just one month of treatment. Then you can retest the numbers. We’ve done this across many beta testers and what we're seeing is that the microvasculature is improving extremely well.
We might see a 20% differential between left and right leg and pull it up to within a 5% differential after only a month of treatment.
At Home Laser Treatment for Joint Pain - How Long Does it Take?
LB: You mentioned one month of treatment. Tell us about what the treatment protocol during that one month period.
FS: The protocol that has been most effective for testers to date is five minutes of treatment on the actual joint, and then five minutes upstream and five minutes downstream. You can then increase that treatment period over time to a maximum of around 10 to 12 minutes for each.
LB: Would you do this every day? And you just mentioned the reader should do this for a month? What happens if you go longer?
“five minutes of treatment on the actual joint, and then five minutes upstream and five minutes downstream”
FS: Yes, everyday, and you can absolutely treat for longer. One month is just the starting point.
LB: It also sounds like you can perform this treatment while sitting still. You can use the Move+ while watching Netflix or playing a video game. It sounds like it's pretty easy to use and it doesn't take a lot of time?
FS: That was one of our core goals as a company, and I harp on it quite a bit with our team. We wanted to build a device that is making the most substantial change possible in the quality of life of the highest number of people we can.
To achieve that, we need to remove inconvenience and make the device as functional as possible so customers can use it on a daily basis. I typically use my Move+ during a breathing and meditation session in the morning.
If you can find something that you do habitually, whether it's a cup of coffee in the morning, or whether it's a routine that you have before going to bed - use the Move+ then. You can use it when you’re moving or sitting down and even when you’re completely focused on something else. It's battery powered, it's wearable, and it's quite comfortable relative to anything else on the market.
The Cost of Laser Treatment for Knee Pain
LB: We are looking forward to trying the Move+ out!
Tell us about how we can get our hands on a device. How much does it cost to get an at home laster therapy device for knee pain and arthritis? And where can you find it?
FS: Right now we are selling for $397. We are also going to offer your readers a discount, in the spirit of self-experimentation!
Get 10% off the Move+
Use the code “longevitymove+“
LB: We are very excited about this 10% discount, which brings the price down to $357USD.
Let’s discuss the price point you just mentioned, for some $400-$500 USD might feel quite expensive. However, there is a story here, and that price point actually represents a real technological advancement.
Similar devices which have been used in a clinical setting cost $15,000 or more. The $400-$500 price point Kineon is offering reflects how you’ve really innovated to deliver this device at such a low price.
FS: Absolutely. It really reflects back to our core mission. We knew we were going to have to get the cost way down. This has to be a device that people can afford to have in their homes, and that they can use conveniently and frequently, or is not going to impact their life the way that it should.
LB: We love that mission!
Where Laser Therapy for Joint Pain is Headed Next
LB: As we move forward and wrap up this interview - we want to end with two things in mind. A forward looking view of where the longevity industry is headed and secondly, what you're doing for your own health and longevity
Let’s start with looking into the longevity future and let's narrow it down in terms of the scope of photobiomodulation light therapy. Where is that going in the next decades specific to health and longevity? What are we going to see?
“with the application of cheaper lasers...we are soon going to be able to track specific molecules in your blood”
FS: We've thought long and hard about this and we see some really good ways to be able to impact people's lives and quality of life in the next 3 to 5 years that haven't been available up until now
We think optical sensors paired with light therapy emitters is going to create many new opportunities. This is the next generation of what you might see on a Garmin watch right now. The green LEDs on the back of your Garmin watch which make for a not so accurate heart rate monitor.
With the application of cheaper lasers and better sensors with some machine learning will be a very powerful combination. We're going to be able to track many new physiological characteristics and even specific molecules in your blood.
We have this capability at the research/hospital level and they will be in your home in the next 3 to 5 years. Kineon plans to be in that space as well, so hopefully we can talk more about this soon!
The Surprising Connection Between Lasers and Gut Health
LB: Brilliant, that's really exciting. You’ve mentioned a few areas where light therapy is producing impressive and unexpected outcomes for cardiovascular health, brain health, but one other you mentioned in the lead up to the interview was gut health.
Tell us, briefly, how there could be a relationship between lasers and gut health?
FS: There's fundamental clinical research into this now using machine learning and mapping bacterial populations in your gut, and even determining the health of that bacterial population.
When you apply photobiomodulation positive outcomes result. For example, different bacterial populations generate different waste materials based on what they are consuming. Early testing in clinical trials with photobiomodulation appears to support healthier gut bacteria.
With our dosing models along with a digital signal processing and machine learning team, we are exploring applications for our light therapy devices in the gut. Watch this space!
LB: That's exciting. If you need a guinea pig, we are all ears.
Forrest Smith CEO at Kineon’s Longevity Strategy
LB: Onto our second question. Share a few of the top things you do when looking out for your own longevity. Tell us about your longevity strategy. Give us one or two things that you're doing each day to look after yourself.
FS: I would say carb cycling and fasting are what I’ve been onto for the longest. I've seen ongoing great results and it's very simple. Fasting and carb cycling has been amazing from a health standpoint.
The Kineon Move+ in action, tipping the balance back in favour of cartilage regrowth & join healing.
Obviously, the light therapy treatments have been helpful for getting myself back into training after injuries. And then there’s daily meditation. I have been doing this for the last five or six years. Pairing that with breathing has been super powerful.
LB: And with that daily meditation, we can now think about adding lasers to the mix! This is a great illustration of what's possible in the longevity feature.
Thank you for joining us today Forrest. There's a lot more to talk about, but for now we're going to head off and play around with the Move+. Our thanks to your team for making it possible to have such a power device in the homes!
FS: Fantastic. Thanks so much. I really appreciate the opportunity to be interviewed on Longevity Blog.
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
What is the Most Accurate Biological Age Test? An Interview with Ryan Smith of Trudiagnostic (Part 1)
Trudiagnostic review: Most accurate Biological Age TEst
How accurate is the biological age test you are currently considering?
Great question, but you also need to ask - how precise is the biological age test?
What do we mean by this? If the difference between these two terms isn’t 100% clear to you, you’re definitely not alone.
The fact of the matter is, choosing the best biological age kit for you is not a straightforward decision, and with more test kits arriving on the market each month - you’ll be glad to know that Longevity Blog is here to help!
In this post, we cover the basics of ‘accuracy’ vs ‘precision’ and in our TruDiagnostic review, reveal why their kit is the best biological age test currently available (plus we score you a discount to purchase one!).
Biological age test technology is moving fast
When investing in a biological age test kit, you’ll want to choose the product which has the best accuracy and precision. What does this mean? We’ll discuss this in detail in today’s interview.
Just like most of the longevity technology sector, biological age testing is advancing quickly.
And while we’ve previously reviewed some biological age testing companies, it is very important to keep you informed of the latest developments.
We have two very important updates for you.
Firstly, did you know that we’ve now moved into the third generation of biological age clocks?
What does that mean? These are algorithms which use longitudinal data collected from the same individuals to see determine how aging occurs over time.
Secondly, many of the first and second generation biological age clocks may have good accuracy, but they are not necessarily great at precision.
To illustrate what this means, if you were to send off three of the same saliva or blood samples to your biological age testing facility of choice, a highly precise laboratory would provide you the same biological age estimate each time. But if they don’t have great precision, you could get three different results.
A graphical representation of accuracy and precision (credit: TruDiagnostic).
For example, if your age is 35 and you get a biological age of 33, 35 and 37, that test kits only has a precision of around 2 years.
So, which results do you believe?
You might be surprised to know that many of the offerings on the market offer precision within 2-3 years.
What does that mean? It means that if you measure your biological age, test an intervention through a self-experiment, and then test again (which is how we recommend you use these kits) - your actual results could get lost in the ‘noise’ with low precision kits.
If this concerns you (and it should!), then you’ll be very interested to hear what our latest interview guest has to say…
TruDiagnostic review video: Hear it straight from the expert, Founder Ryan Smith.
latest developments in Bioaging with trudiagnostic CO-FOUNDER RYAN SMITH
Ryan Smith the Co-Founder and VP of Business Development at TruDiagnostic.
But don’t let his ‘business’ title fool you - he is exceptionally knowledgeable on the science behind epigenetic testing.
Ryan is a biochemist who founded Tailor Made Compounding, which became the 4th fastest growing company in healthcare in the US at the time.
In late 2019, he saw tremendous potential in epigenetic testing and analysis and co-founded TruDiagnostic, who now offer once of the most accurate and precise biological age test kits on the market.
Today, we ask him to walk us through these important developments in biological age test kit technology. Strap in and put your thinking caps on!
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with TruDiagnostic, we have a negotiated a 12% off coupon code for our readers.
Use the code longevityblog at checkout and save!
This interview was conducted in August 2022 over Zoom and is an audio transcript with edits for clarity, brevity and correctness.
How do you estimate biological age?
Ryan Smith, Vice President of Business Development at TruDiagnostic is a wealth of knowledge on the latest developments in biological age testing. In this interview, we first explore the development of biological age ‘clocks’ and what it means for these clocks to be accurate and precise.
Longevity Blog (LB):
Ryan, thanks so much for joining us today. We have a very common question that we'd like to ask you to kick things off. And it's an important one, lots of people ask it:
How do you determine your biological age? Could you give us a general answer?
Ryan Smith (RS): Certainly! I think that the answer has changed throughout time. The search for biological age has always been important because of something called phenotypic variation - there's a lot of difference between how people in the same chronological age group age differently.
This definition of biological aging, searching for how the body is aging was very crude initially. Things like the number of your chronological age plus the number of packs per year you smoke, as a biological age. But as we've gotten more sophisticated they’ve culminated in epigenetic clocks, which are probably the most sophisticated methods to determine biological age.
Even these have a little bit of a history where they've continued to improve. Right now, what we're essentially doing is creating algorithms to predict someone's biological age. And we do that by having a cohort that we train these algorithms and then a separate group as a validation cohort. That's what we've done with epigenetic clocks, and it's why they're generally the most predictive of negative age related outcomes and why they're so powerful.
What is an Epigenetic Age Clock?
Epigenetics instructs your DNA on how to be expressed. All cells contain all of your DNA, but how do they know to be a liver cell, or a brain cell or a skin cell? Epigenetics is where this information is stored.
LB: You've mentioned “epigenetic clocks”, briefly remind our audience what these are.
RS: Epigenetic clocks are essentially a biomarker measurement. Age clocks can be created using any type of data set, but here the data that we're measuring is an epigenetic methylation.
For those of you who aren't familiar with epigenetics, it essentially is the regulation of your DNA.
Every single cell on your body has the same DNA sequence, it's what makes it individual to you. But how that DNA is expressed is different from cell to cell. It's why your skin can behave like skin cells and your heart can behave like heart cells. This is determined by what genes are expressed or turned on.
What we're measuring is DNA methylation, which is the off switch, generally, for most of those DNA expressions. We have a lot of DNA methylation in our cells, with over 29 million spots in each cell, which can be methylated. And every cell is different. So it's a lot of data.
Epigenetic clocks have been created by seeing the differences in aging at these different locations across individuals. And then creating a predictive algorithm to see if we can predict that change with age and see how close we can get to variables, like someone's chronological age, for instance.
How Do You Determine Biological Age?
Methylation of the DNA is the on or off switch for DNA expression. There are over 29 million ‘CpG’ sites in your genome where methylation occurs. The patterns of methylation change with aging, and therefore they make an excellent predictor of how old you are biologically.
LB: Biological age clocks have been around for about a decade, and they’ve advanced very quickly over the last few years.
Can you introduce us to this concept of the “generations” of epigenetic clocks that have emerged and an approximate timeline?
RS; The first ever biological age clocks came out in 2011, with the first really widely applicable clocks created by Dr. Steve Horvath at UCLA in 2013.
I will go on record by saying I think he might be nominated for a Nobel Prize for this work. It is really groundbreaking, because, for the first time, we're able to read with a very high accuracy: the age of someone's body.
The clock was originally created by looking at those epigenetic methylation changes across a few thousand patients and looking at what markers were most significantly changed with age. Some locations might have no methylation at young adulthood, but as as we get older, significantly more methylation or vice versa.
That's how he was able to create this predictive algorithm. But it was trained to predict someone's chronological age. Originally, it was used for really interesting applications, but not necessarily health applications.
One example is collecting DNA at a crime scene to see how old a criminal might. In the case of the refugee crisis with Syria, it was used to see if people were adults or minors, and therefore eligible for asylum.
How Does Biological Age Testing Work?
Our Founder Nick has tested the TruDiagnostic product, and was very impressed with the wealth of knowledge TruDiagnostic provided through just a few drops of blood!
LB: But the new applications in health began to emerge, as ‘older’ individuals were connected to poorer health outcomes. Tell us about this transition.
RS: The research field started to notice a pattern, which is that those people who were older with this test than their chronological age, were at significantly increased risk for negative health outcomes.
While those people who were younger than their chronological age, were protected against those same outcomes.
They discovered, for example, that being seven years younger biologically than chronologically reduced the risk of morbidity and mortality by 50%. So that was the first generation of age clocks.
Generations of Biological Age Test “Clocks”
LB: That's a little bit of a complicated concept that you're introducing here, so let’s make sure we make this very clear for the reader.
First generation clocks weren’t developed to predict risk of poor health outcomes, but in their application were discovered to be capable of doing this.
Now, with this realization, we begin to see the development of ‘second generation’ clocks which are designed to be predictive of age related health outcomes. Is this correct?
RS: Exactly. An important concept here is “hazard ratios” for disease. This is essentially the likelihood of developing a particular outcome. You can have hazard ratios for anything. You know, that hazard ratio for it raining, for instance.
For disease, the higher the hazard ratio, the higher your likelihood. Ideally, the bigger the change in the biological age, the bigger the change in hazard ratio. That's exactly what we're seeing as these biological age clocks get better. “Second Generation” clocks are now being trained not on chronological age, but on biological signals.
LB: Have the inputs to second generation clocks changed? Are there new variables which are being considered in the training datasets with second generation clocks?
“the key characteristic of the third generation of biological age clocks is using ‘longitudinal’ data sets, which follow the same person over time”
RS: In the second generation clocks, we have started to measure things like your blood based biomarkers that we know change with age.
For example, your red cell distribution width, your immune cell types and distribution, or your serum albumin. These are all things that change as we get older.
Then, for third generation clocks, which is really where we're at now, they did the exact same thing, but they did so longitudinally. So instead of looking at a lot of different patients over a lot of different time points, they looked at the exact same patients over a long time period.
By analyzing data longitudinally, we are able to get rid of other confounding factors, things like environmental exposures. For example, if we get these from a biobank, the amount of antibiotics that someone was exposed to 40 years ago might have been a lot less than what we're exposed to now. And vice versa. Another example is leaded gasoline instead of unleaded gasoline.
By looking longitudinally, you can sort of factor those things out, because you can sort of assume that the population you're looking across time has had similar exposures, especially if they're living in a similar area. And so what we're starting to do is to now get rid of all of these confounding factors which might be taking away sensitivity and specificity from the biological signals of aging.
A graphical representation of the concept of generations of biological age clocks. For more information, you can read this scientific study.
LB: So the key characteristic of the third generation of biological age clocks is using ‘longitudinal’ data sets, which follow the same person over time, and understanding how that biological age is changing over time based on environmental factors and tracking blood based parameters? Second generation clocks are missing this ‘longitudinal’ data.
RS: Correct. There is really only one third generation algorithm that currently exists, DunedinPACE. This clock uses 19 blood related biomarkers from a longitudinal study, where they tracked gum health, for instance, and leukocyte telomere length, which has classically been a very popular marker for biological age.
Biological Age Tests: Accurate or precise?
“Precision is very, very important, especially on a personalized medicine aspect. If you have a wide degree of technical variation, you’re just not sure if the change you’re seeing is real biologic change, or if it’s just noise.”
LB: TrueDiagnostic have differentiated their biological age test from other providers by offering the market’s only third generation clock.
Tell us why this algorithm is better for biological age predictions in very simple terms.
One of the things you shared at pre-interview is the ability of this clock to consistently make the same predictions off the same sample data. Maybe start there.
RS: We've already talked a little bit about how to judge an aging clock’s accuracy, right? Which is generally more predictive of negative health outcomes? The other thing we want to always talk about is precision of the algorithm. We want it to be both accurate and precise.
This has been a very big problem, actually, for these epigenetic clocks to date. One of the reasons I think early adopters have been a little bit disillusioned with these second generation tests is because they've had wide variability.
For instance, even with Dr. Horvath’s original algorithm he created in 2013, if you took the exact same sample and tested it twice, you could have up to 3.9 years of variation from even the same sample. That's a huge problem, because if you're looking to use this for reliable information to judge things like interventions, you wouldn't be able to test within a period of 3.9 years in order to get a statistically significant outcome.
Precision is very, very important, especially on a personalized medicine aspect. If you have a wide degree of technical variation, you're just not sure if the change you're seeing is real biologic change, or if it's just noise.
What is the Most Accurate Biological Age Test?
The ICC (intraclass correlation coefficients) score represents precision. How consistent is a given biological age clock at reproducing a biological age prediction off of the same sample? At far right is the algorithm used by TruDiagnostic, showing how precise the algorithm is compared to other methods.
LB: Okay, so there's some complicated concepts you're talking about there, we're discussing the difference between precision and accuracy.
You've gone into some detail about some of the limitations of second generation clocks, and where this newer third generation has a bit more precision.
Generally, when people are trying to make a decision about a biological age test, they'll ask a question that's a bit more simple, or perhaps even naive of some of these details between terminology for precision versus accuracy. They're going to ask, “Which biological age kit is most accurate?”
If you're talking to that layperson, what do you tell them?
RS: Whenever you get the results of any biological age test - you want it to be informative about why you think they asked the question in the first place. I think for most people it would be - Why do you want to quantify aging in the first place? The answer is that biological age is the biggest risk factor for most chronic diseases and death.
So if you want to quantify a risk factor, usually, it's because you want to change it right? And so in order to measure that, you really want it to be predictive of outcomes. So the most accurate clocks are going to be the ones that get higher when you're going to have worse outcomes for all age related markers. And as they get lower, you're gonna have more positive outcomes for all age related markers.
And the way that we measure that is called a hazard ratio. What is your likelihood of getting a particular disease if you're aging at a rate of one versus if you're aging at a rate of 1.1? And in General, the higher the hazard ratio, the more predictive and so I would measure accuracy by its ability to be associated with health outcomes.
There are Different Types of Biological Age: Extrinsic vs Intrinsic
An example of an intrinsic biological age test kit is GlycanAge, which tracks inflammation in your body by analysing your glycans. What are glycans? How can you use intrinsic age to self-experiment, why not read about it here?
LB: Often, biological age is discussed as if it's one number. But one of the things that we've learned through engaging with your testing kit and platform is that there's two big categories of biological age.
Extrinsic biological age and intrinsic biological age. So far, we've been talking about extrinsic biological age.
Tell us about intrinsic biological age.
RS: At the cellular level, biological age measurement is different in every cell. Your skin cells are going to be very different than your heart cells, in terms of what genes are turned on, and turned off. So ideally, if we were to do this test, we would do it on a single tissue type and that would be the most precise and accurate way to develop an algorithm.
But the problem is that for most of our body, we have a whole combination of different tissues making up any given organ. In our skin, we might have keratinocytes, cells, as well as fibroblast cells. In our blood, the majority of the DNA is from our immune cells. These include things like CD8 T cells and CD4 T cells, your monocytes, your basophils - you know, all of these different cell type markers.
TruDiagnostic’s Immune Age ReporT: An Intrinsic Biological Age
LB: So in simple terms, intrinsic biological age can be based on different cell types representing a given organ or systems in the body.
In your TruDiagnostic report, you've focused on the immune system for the extrinsic biological age.
There's this important concept in biological aging known as immunosenescence, which is the decline of immune system age. Talk to us about this process and how looking at an intrinsic age can help us understand how we are aging biologically.
From a TruDiagnostic ‘Immune Age’ report, a graphical representation of immunosenescence.
RS: As we get older, one of our most important immune organs, the thymus, starts to degenerate. We lose thymic volume and as a result that changes the amount of immune cells which are circulating in our blood.
This means the immune system generally becomes worse at doing its job, and isn’t clearing things that are not supposed to be in the body. Being able to quantify immune cell changes allows us to quantify the aging process in a different way.
We can gain a bit of insight into how the immune system is aging. One important measure is the ratio of CD4 to CD8 T cells. We would usually see this decrease as we get older - so the decrease in this ratio can be used as a snapshot of your immune system’s aging.
LB: Would it be accurate to say that extrinsic biological age is more responsive on a short term basis to interventions?
RS: Yeah, certainly. I think that the answer is we definitely see more variation on a day to day basis. These changes that are happening in your blood are happening at a very large scale and new changes are some things that we can detect. This biomarker can be trained for a wide variety of things.
LB: Thank you, Ryan.
TruDiagnostic are also providing an estimate of how fast you are aging….
Read Part Two of the Interview Here
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Regrowing Knee Cartilage and Restoring Joint Health Naturally. An Interview with Kineon CEO Forrest Smith - Part 1
Can you regrow cartilage?
New things are possible for your joint health, as the next generation of ‘at home’ light therapy devices hits the market.
Could the Move+ from Kineon heal your knee/joint pain? Yes, it certainly could. Read on for more…
Can you regrow cartilage in the knee without surgery? Can you regrow cartilage at all?
This is a very popular question on Google, but unfortunately, if you’re searching for this answer - you don’t get many promising solutions.
Some will tell you - No, you cannot regrow cartilage, full stop. Others list some promising prescription drugs that might work, some day maybe.
Well, that doesn’t lead to much hope for sufferers of osteoarthritis, or those who are asking - Can you regrow cartilage in the knee without surgery?
People looking for answers to questions like these might feel like they are chasing a medical miracle. They might even experience feelings of hopelessness or despair.
Well, guess what, it’s 2022 and longevity technology development is moving faster than ever. Rejuvenating technologies that make living a younger, healthier life for longer are rapidly emerging.
So you’ll have to excuse Google for being a bit behind the times - but there’s a new kid on the block, and it just may mean that it is now possible to regrow cartilage in the knee naturally.
And it doesn’t stop there - but let’s not get too ahead of ourselves. We need to cover a few basics, up front.
Can you reverse cartilage damage?
At left, a healthy knee joint. At right, an arthritic joint with cartilage degradation. Note the widespread inflammation. Image source: Wikipedia
Let’s start off with some important details about cartilage, beginning with several common myths about cartilage.
Osteoarthritis myths
Arthritis is simple “wear & tear”
Arthritis doesn’t heal.
Cartilage doesn’t regrow
Exercise makes it worse
None of the above are true, yet most people believe them.
This does not take away from the pain that many millions of people around the world experience due to joint degradation. That is 100% real.
In fact, joint health is a major longevity issue, and looking after your joints is an essential part of your longevity strategy.
Patients with severe pain due to osteoarthritis stop walking and moving regularly. They often suffer from accompanying illnesses such as depression and cardiovascular disease.
And when it comes to longevity, being able to move your body is absolutely essential to your quality of life. Walking speed, calf strength, aerobic fitness - the list of ‘longevity metrics’ related to joint health goes on - you need to be looking after you body’s ability to move to stay healthy and live long.
Cartilage Regeneration is about Balance
To better understand cartilage regrowth, we need to stop thinking about cartilage as a finite resource that you use up, and instead see it as part of a balancing act.
In our interview today, we’re introducing you to a new partner company Kineon and their CEO and Co-Founder Forrest Smith, who had this to say:
As you age cartilage may grow more slowly, but it never really stops. What happens instead is an imbalance, typically in joints, of growth of new cartilage versus cartilage degradation. Especially if you have long term chronic inflammation, or osteoarthritis. It’s this osteoarthritis that causes the degradation of the cartilage.
By reducing inflammation, you're reducing the degradation rate of the cartilage. And that means your body can build that cartilage back faster. So it is actually on both sides of the equation, it is a balancing act.
So if you are suffering from a lack of cartilage in the knee or another joint (like the hip or shoulder), you need to reconsider your own cartilage balancing act.
And here is where it gets exciting - and where new technology is now available to help you with both sides of the equation.
Kineon’s Move+ is a brand new product which leverages decades of research on light therapy, recent advancements in the cost and quality of lasers and a new, very driven team of experts who have created a device designed to help you reduce inflammation and boost cartilage regrowth.
If you’re keeping track, that means you’re seeing improvements on, as Forrest said above, “both sides of the equation”.
Kineon MOVE+, Does it Work?
To date, early testers of this device have been completely ‘wowed’ by the effects they’ve seen (scroll down on the Kineon homepage to see testimonial videos) on their levels of pain and restoration of function in joints which have plagued them for years and even decades.
Kineon’s Move+ - a light therapy device which relieves joint pain safely and quickly by stimulating factors which support healthy joint cartilage.
They are a very promising sign that it may be time to re-think the answer to the question - Can you regrow cartilage in the knee? It’s simply not a hard “No” anymore.
And for those who have long suffered from joint pain, there may at last be hope again.
But, as is our usual preamble - at Longevity Blog, our job is to put such claims to the test! We’re here to help you get your hands on a device at a discount and guide you through testing before & after to quantify the results yourself.
We also ask the tough questions of the founders and lead scientists at longevity tech companies, to help you cut through the marketing and onto the results.
So, our fellow joint health enthusiasts, let’s hear more from Forrest, CEO at Kineon…
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with Kineon, we are please to offer a 10% off coupon code for the Move+, exclusive to our readership
Use the code “longevitymove+” at checkout to save 10%!
This interview was conducted in June 2022 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Longevity Blog (LB):
Forrest, welcome to Longevity Blog! It's one of the most common health questions on Google, full stop.
So I'd like to start by asking - can you regrow cartilage? The answer to this question is a very important one for our longevity. In particular, people are interested in regrowing cartilage in the knee without surgery.
What's your answer to this question?
Forrest Smith (FS):
Thanks for having me! As you age cartilage may grow more slowly, but it never really stops. What happens instead is an imbalance, typically in joints, of growth of new cartilage versus cartilage degradation. Especially if you have long term chronic inflammation, or osteoarthritis. It’s this osteoarthritis that causes the degradation of the cartilage.
By reducing inflammation, you're reducing the degradation rate of the cartilage. And that means your body can build that cartilage back faster. So it is actually on both sides of the equation, it is a balancing act.
There are two primary ways to improve cartilage growth, which are well established in the medical literature. The first is increasing the rate of collagen type 2, which is a building block for the extracellular matrix that is the framework or the infrastructure for the cartilage to regrow.
The second is by boosting mesenchymal stem cells activity, which differentiate into building blocks for cartilage.
Interestingly, when you apply light therapy, these stem cells are encouraged to create the infrastructure for building cartilage.
YES, YOU CAN REGROW CARTILAGE
LB: Thank you for the detailed answer there. What we are hearing is a “yes” to this question - can you regrow cartilage. But the answer, as with many things in biology, is not that simple. The key concept here is that of balance.
By minimising the degrading your cartilage in your joints, and boosting the things that rebuild the cartilage in those joint, we can have positive cartilage growth.
Your company Kineon is has built some very interesting technology for improving this balance in the favour of cartilage growth. But to understand it, we’re goint to need to introduce a few new terms to the audience.
One of them is photobiomodulation, which we'll jump into in some detail coming up. The other one you just mentioned is mesenchymal stem cells. A lot of our readership knows about stem cells, stem cell therapy is popular in longevity.
Let's talk in a little bit more detail about mesenchymal stem cells. Tell us about them and how they are involved in cartilage growth and repair.
LIGHT THERAPY FOR JOINT REPAIR
FS: Mesenchymal stem cells can turn into almost any other other type of cell. They're a very useful building block for your body. You generate them primarily from your bone marrow, deep within the bone.
What we are seeing in the medical literature is that by using light therapy, mesenchymal stem cells are more likely to differentiate into cell types which support cartilage and bone growth.
“when you apply light therapy, these stem cells are encouraged to create the infrastructure for building cartilage”
LB: Great, thank you. And so what we're hearing to summarise, is that in terms of answering the question, Can we regrow cartilage in the joints? Or can we regrow cartilage in the knee? - we need to think about the balance.
So we should focus on reducing the amount of factors that are tearing down cartilage and increasing the number of factors that are building it back up.
Mesenchymal stem cells, which are produced in the bone marrow that differentiate into bone and into the cartilage are important to support and boost cartilage regrowth and repair.
The Kineon Move+ in action, tipping the balance back in favour of cartilage regrowth & join healing.
Let’s now come back to the research that you're mentioning and our next new terms - light therapy or photobiomodulation. Tell us a little bit about what this term means?
FS: Photobiomodulation is a bit of a blanket term. Originally, when light therapy was being researched, there were a couple of terms that were used by the scientific community.
The medical and scientific research community can get a little bit divisive about terms. It sounds extraordinarily technical, relatively what it actually is, but it's basically putting the lasers, LEDs and everything using light to interact with biology under one roof.
Photobiomodulation - How Does it Work?
LB: Okay, so it's an all encompassing term photobiomodulation. What we find most interesting about the term is the ‘bio’ part. The medical literature you are referring to has shown in various ways that the application of light to the body is impacting how it works at a cellular level.
Can you comment on this? In particular, the interaction between stem cells and joint cartilage?
Image credit: quitemindfm
FS: This is a really good segue into some of the fundamental mechanisms behind how light therapy works.
The research up until recently had indicated that the primary mechanism of function for the photobiomodulation was the light impacting molecules in the phospholipid bilayer of your mitochondria.
Effectively light therapy promotes a more effective and more efficient use of energy in your mitochondria. This is one of the primary drivers of the outcomes
But it's not the only one, and more recently there’s been a few more mechanisms of action discovered…
LB: We are excited to hear about these Forrest, but before we do, it is important to emphasise that it is very well established that light interacts with our biology.
One of the primary mechanisms for doing so is by stimulating mitochondrial energy production, as you’ve just mentioned.
The Move+ from Kineon uses both lasers and LEDs to direct light therapy into the joint safely and effectively.
This is why there have been many ‘red-light therapy’ products entering the longevity and wellness marketplace over the past decade. Most of our audience will be familiar with these.
LED light type therapies that their favourite biohacker on instagram might stand in front of, or perhaps shining red light on your face to boost collagen production, or maybe even using red light therapy on your shoulder or back to relieve aches or pains.
Kineon’s Move+ - A Next Generation Light Therapy Device
What we want to emphasise is that the light therapy product Kineon has brought to market - the Move+ - stands out from these types of light therapy for several key reasons.
Not only is it a therapeutic device modelled after units used in the clinical setting, but it is also using both lasers and LEDs at the same time, to stimulate these ‘multiple mechanisms’ of action, not just mitochondria.
Let’s look deeper into the differentiators here. Firstly, talk to us about how you're using two types of light therapy in the device.
Our Founder Nick is self-experimenting with the Move+ over the next two months, to see if it can help him recovery from a triathlon over-training injury. Be sure to subscribe to hear about the results!
FS: One of the problems in the literature, which is only recently improving (over the last 3-5 years), is that medical researchers didn't really understand the technical side of the equation (e.g. light coherence, wavelength, intensity) and at the same time, the technical side didn't understand the medical physiology.
What you ended up with was a number of papers that were reporting the data that was easiest for them to report and so you had inconsistent metrics measuring the optical parameters of the light.
We've spent a lot of time dialling into what the technical and physiological terminology and metrics mean. Essentially the Rosetta Stone for all of these earlier meta medical trials. This has allowed us to interpret the many different medical research trials and know the ‘dosage’ of light for a given application.
What is Dual Therapy? Laser and LEDs
LB: Bringing it back to the Move+ product, you’ve incorporated a dual therapy including both LEDs and lasers in the same device. You’ve implemented this unique design after comprehensively reviewing and translating results from across widespread research literature, which support this ‘dual therapy’ approach.
FS: That's exactly right. The most important part of the problem is getting the dosage of light correct. For this, you have to know the amount of photons that you're putting out and how they're being put out.
LEDs emit light in essentially a spray, just an open spray in all directions, it's called a lambertian emission pattern. They're typically packaged, or bonded, into a cup, which contains them to a 120 degree emission pattern. But what we've done is we've actually pulled those LEDs even tighter with our own proprietary optics down to 30 degrees. This ensures the right level of penetration.
We're using LEDs for our deep red at 650 nanometers and our lasers are a near infrared wavelength at 808nm, which is the most proven and the optimal balance the photobiomodulation impacts we are targeting
“we know exactly how deep we’re dosing and how much light is going into the tissue, targeting microvascular level effects”
LB: This is a great opportunity to mention a few more of these mechanisms of action, specific to these wavelengths and the LED therapy.
Light therapy boost circulation
FS: There's also impacts for haemoglobin. When this red and infrared light hits haemoglobin, it strips out nitric oxide. Nitric oxide has some really powerful impacts on your physiology. It dilates blood vessels, providing more blood to tissue in areas where it's become stagnant. Here it is important to target a certain depth into the tissue.
With the Move+ we know exactly how deep we're dosing and how much light is going into the tissue, targeting these kind of microvascular level effects. The LEDs spread of light opens up the microvasculature. Then the penetration from the lasers and the infrared deep into the internal tissues provide a really powerful combination.
LB: That's the dual therapy combination right there. We really want to talk more about the lasers but before we do, first let’s cover one more topic on the LEDs and red light. Explain to us a bit more about how this specific LED wavelength is opening up microvasculature and improving blood flow and therefore tissue repair.
FS: Having the right wavelengths of red and infrared light at the right depth where your microvascular sits around your joints brings fresh blood because stripping out nitric oxide dilates those blood vessels. This means blood flow increases in the area.
LB: Can you give us an example of this effect? Some evidence as to why this is important for healing?
Injury Can Drive Cartilage Loss
FS: One of the things that you see with chronic tissue damage in joints happens typically after some kind of traumatic joint tissue damage, like an ACL tear, or meniscal tear, or even sprains. The inflammation from this injury doesn't just stay contained to the joint, it actually also damages the microvasculature around the joint as well.
Are you an athlete? Looking for other ways to recover more effectively. You might really like what we have discovered about a new longevity supplement - Urolithin A. Read about it here!
There was a study of 3000 NFL players where 50% had an ACL tear and 50% did not (control). In the group with the ACL tear, the tissue temperature in their damaged leg quadricep was two degrees lower than the tissue damage in the healthy quad. Surprisingly they also had a 50% increased risk of severe cardiovascular disease afterwards!
What this data is showing us is that, not only is the tissue damaged in the joint, there is also long term inflammation generated throughout your body and even into your cardiovascular system. This means damage from an endothelial standpoint, stiffer veins and arteries and long term negative impacts in overall health.
So, when you're treating joints with light therapy, you're not just treating the joints, you’re also improving the upstream and downstream microvascular. So that you can actually stop having that trickle of inflammation that adds up over time.
LB: In our background research on cartilage degradation, we found that previous injury was one of the major causes of cartilage degradation. The development of lesions (areas of acute damage) in the cartilage or even damage to a ligament often sets up the degradation of cartilage years later. Severe loss of cartilage can limit mobility, and this is where we really get into the longevity part of the picture
What we're hearing about the right type of red light LED treatment is that this opening up of the microvasculature is getting fresh blood flow into these areas and reducing inflammation. But we’ve not yet heard about cartilage or internal joint repair, is that where the lasers come in?
Laser Light Therapy Penetrates Deep into the Joint
FS: The laser allows treatment of the synovial fluid and the tissue inside the joint directly, which is not something that you're really going to be able to do with the LEDs. If you have an LED only device, it's definitely better than nothing. But it's not penetrating the internal tissues.
Lasers emit as a column of light and work really well for dosing internal tissues. Our light propagation models have shown us that with the Move+ laser, the internal tissue is receiving the correct levels of dosage. It would take an unthinkable amount of LEDs to reach that level of penetration.
LB: The laser allows for deeper penetration into the joint as a whole, but it is both of these light emitting technologies (LEDs and lasers) together that help rebuild healthy cartilage.
But there's a key aspect of this that you've just touched on - biphasic dose response. That term sounds a little bit complicated and might be intimidating to the reader, but essentially what it means is that there's too much of a good thing and there's too little of a good thing.
There's something in the middle that we want to hit with the Move+ treatment protocol. Can you first tell us what a biphasic dose response is, and then, secondly, how you've used that information to get the right amount of light into the joint for healing/repair?
FS: I think you've done a great job of explaining it. There is essentially a curve where the amount of dosage delivered is on one axis the results are on the other axis.
As the amount of dose increases, it's going up a hill until there's an optimal point at the top. Then it goes back down that hill. We've spent a lot of time on our light propagation models so that we can justify the correct dosage from the Move+ device.
Early Testers of the Move+ are Making Impressive Claims
LB: What your team is doing differently is that you’re thinking specifically about joints and merging multiple types of light therapy technology with very specific calibration to have very specific healing effects in that joint. With the right dosage, you’re increasing blood flow, improving synovial fluid health and increasing the activity of the mesenchymal stem cells.
Ed says knee pain was greatly limiting his life, but the Move+ gave him his life back. “It just transformed my knees”
You've had some pretty interesting success with early testers of this device and have some very convincing testimonial videos. Do we have enough information to know you've gotten these dosage models right?
FS: We have enough information to know that we've done better than any of the other light therapy offerings out there. But I think we still have work to do.
One of the things we've seen from our early testing with beta users, that I think will speak to your audience from a longevity standpoint very well, is that when we're treating large tissue masses (e.g. the leg), we're not just seeing the nitric oxide rise in that area, we're seeing it all over the body.
This means your serum levels of nitric oxide are getting much higher and the benefits of that stay in your system for you 24 to 72 hours. This has a really positive effect on your endothelial tissue and keeping that healthy is one of the best things you can do from a cardiovascular standpoint. That's also particularly true with your brain.
We're seeing very high levels of nitric oxide crossing over to the brain, which improves vascular health in your brain.
Would the Move+ Work for You? There’s only one way to find out…
LB: These are some very interesting systemic results! We’ll be following up on them.
Coming back to the beta testers - using the Move+ on yourself and testing how it might work for you is what this audience loves to do. It's one of the things that we focus on.
Often I'm the guinea pig, but increasingly others are doing the same and sharing the results with us. The Move+ seems to offer great opportunities for self experimentation. Let’s consider a reader who has, say, a shoulder or a knee issue and is interested to try the Move+. …
INTERVIEW Part 2 AVAILABLE HERE!
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
One Skin Before and After - Skin Aging in the Future: An interview with OneSkin CEO Dr Carolina Reis - Part 2
Reverse Skin Aging with OneSkin
Can you reverse the age of your skin naturally?
This is a very popular question. After all, who doesn’t want to look younger?
More important than looking younger, however, is the need to reverse or delay the age related decline in the health of your skin, becoming known as your skinspan (the healthspan of your skin).
Consider that your skin is your largest organ, and it plays a very important role in overall bodily wellness and longevity, much beyond how you look.
In fact, the senescent cells associated with skin aging are known to trigger age related inflammation beyond your skin, throughout other areas of the body.
Talk about beauty that is more than skin deep! If we want to maximise healthspan and look out for our longevity, intervening in the aging of our skin is key.
Interestingly, the focus of our second part interview with Dr. Carolina Reis, CEO Of OneSkin, is precisely targeted at this question. Can you reverse the age of skin?
Or perhaps the more targeted question YOU really care about - can you reverse the age of your skin? And how would you know if you did?
The team at OneSkin seem to think this is possible. And they are making some series headway on proving it. Consider the following claim, made on their website:
OneSkin’s scientists screened over 1,000 peptides for their effects on skin’s biological age and discovered a proprietary peptide: OS-01, the first peptide proven to reduce skin’s biological age! OS-01 powers all of OneSkin’s products and takes the guesswork out of choosing effective anti-aging products.
OneSkin OS-01, a topical supplement focused on your ‘skinspan’ - aka the healthspan of your skin.
At Longevity Blog, our job is to put such claims to the test, by helping you to test before & after results yourself. We also ask the tough questions of the founders and lead scientists at longevity tech companies, to help you cut through the marketing and onto the results.
Let’s do just that.
OneSkin: Can it reverse skin aging?
As we covered in part one of our interview with Dr Reis, there appears to be some real science behind this biological age reversal claim.
This is because OS-01 is not your typical skincare product. Instead, it is a topical supplement, one that may actually help your skin to become younger, at least as far as biological age is concerned.
We cover the details behind why OS-01 can produce such results in interview part one. In part two, we ask Dr. Reis - how can you test this claim for yourself?
To learn more, let’s continue our 1:1 interview with OneSkin CEO and Co-Founder, Dr Carolina Reis.
OneSkin Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with OneSkin, we have a negotiated an industry leading 15% off coupon code for our readers.
Use the code longevityblog at check-out!
May 2023 Update
Our Founder Nick self-experimented with OS-01 FACE and had some very impressive results.
See his face before and after using high resolution facial scanning technology at 6 months and after 12 months!
This interview was conducted in February 2022 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Have you read Part One?
OneSkin Before and After
Longevity Blog (LB):
Give us some advice on how our readers can run a self experiment and come to the conclusion - yes, OS-01 helped my skin be healthier.
Dr. Carolina Reis (CR): We continue to search for a method that can be quantitative and we still don't have it, unfortunately, to offer to consumers.
We do have the molecular clock (MolClock, more on that shortly), but it's not a consumer friendly testing method primarily because requires a skin biopsy to access skin biological age changes.
So I would say to start by taking pictures, making sure that's you use the same light and same time of the day. Take these every two weeks and every month and compare side by side.
For the future, we are trying to develop a method that ideally would be non invasive. Perhaps using a tape stripping, where you could collect samples from your skin and we could predict your skin biological age.
OneSkin How to Use It
LB: First off, whenever you need guinea pigs for your biological skin age, we are happy to participate!
How long should our readers run that self experiment? What is a long enough period to evaluate before and after?
CR: We don't know yet, exactly. For example, right now, we are running this clinical study in which our primary goal is to measure the change in the skin biological age. And we have the participants using the product for six months, up to a year.
Our Founder Nick is using a before & after approach to validate OS-01 on his skin using a Visia scanner. He is retesting at 3 months.
August 2022 Update: Nick’s results are in and you’ll be shocked
We need to collect biopsies and sequence the DNA, isolate the DNA and then measure the skin biological age before and after treatment. We do know the process of improvement is incremental. Soon we will have good data from this clinical study.
We get a lot of feedback from our customers with testimonials around the improvement of dark spots and sun damage. You can certainly see this from pictures. Some see improvement in three months or less.
The clinical trial level of rigor is six months. We've heard from users benefits can be seen after three months.
LB: Just to contribute to the discussion, our plan is to have our Founder Nick test the product for three months with before and after assessments from a Visia scanner
Biological Age of Your Skin
“Our goal is to use this skin biological age measurement as our reference to see if our products is working.”
LB: Let’s quickly address the MolClock and what you just described in terms of skin biological age. This is a very interesting concept. What is MolClock? And where do you think this concept of skin biological age and measuring it is going in the next few years?
OneSkin’s MolClock is a first of its kind. Estimate the biological age of your skin through an epigenetic analysis.
CR: Every tissue in our body has its own biological age, which is often different from our chronological age. Depending on your genetics, on your lifestyle, you can have a higher or lower biological age compared to your chronological age.
What matters, in the end, is your biological age, because that reflects the health of your tissue. We are always aiming to have a lower biological age. The good news is that biological age is changeable.
Our goal is to use this skin biological age measurement as our reference to see if our products is working. We do this by reading the DNA of the skin and using an algorithm that can estimate skin biological age. Once we have that we can test products to see if they are reducing it.
Our current algorithm is called MolClok, which we trained with more than 500 samples of skin from which we know the chronological age.
LB: This sounds like you’re looking at the epigenome?
CR: Yes.
LB: Great. Thank you for that follow up and example.
Let's extend that a little bit to where you think this technology is going. Specifically, where OneSkin as company is going over the next 5 years?
OneSkin is a Longevity Technology Company
CR: OneSkin is a longevity company. The fundamental approach of our technology is to understand aging and to develop interventions that can target and reverse aging.
The first application for the OS-01 peptide that we discovered is to target skin aging and to improve skin health. But eventually, we will test and expand the use of this peptide in other age related conditions.
Because we are targeting senescent cells – which are a driver of aging in many tissues and the root cause of many age related diseases - we believe we can treat other cells/organs as well.
For example, in adipocytes (fat cells) we hope to decrease the senescent cells there to treat, for example, metabolic conditions like obesity. There are many opportunities to understand if this peptide can be translated to other applications.
One Skin have compiled an early, but convincing body of research supporting the rejuvenative effects of OS-01 in human skin. Read more on the One Skin website.
Even more, a systemic application, where we would potentially treat our whole body and prevent the accumulation of senescent cells and maintain the health of our tissues as we age in order to avoid age related diseases.
OneSkin we will not only test other applications for this peptide (OS-01), but will also continue to research new molecules and new interventions as this science evolves. We want to be the company that offers a one stop shop for longevity.
Obviously skincare will be our core business. But eventually we can expand, for example, to hair treatment/hair loss and potentially other conditions. Our main goal is to help our consumers to age at their best with products that are scientifically validated to optimize health. That's the goal.
Dr Reis on the Longevity Future
“I envision a future in which we’ll be able to control or fine-tune aging at the molecular level. We’ll be able to actually regulate the aging process. ”
LB: That's a grand vision and will get our readers very excited. You just talked about skin aging, hair loss, fat tissue, and these being driven by cellular senescence. This all fits into a bigger picture for longevity technologies over the next decade and more.
Add to that narrative for us a bit. Where do you think this industry is going, led by visionary CEOs like yourself? Look at the 5 to 10 year horizon, tell us what you see.
CR: I'm so excited about that, too, because so much has changed in the past 5 to 10 years. I can clearly see how fast we will experience those changes happening in the next few years.
I envision a future in which we'll be able to control or fine-tune aging at the molecular level. We'll be able to actually regulate the aging process.
For example, the science of cell reprogramming, the fact that you can reprogram a cell to go back in time, and to go back to a younger state is definitely promising. I do believe that those technologies will get to a point that we can offer them to consumers to extend our time in good health.
Skin age is just the first target for OneSkin. In the near future, the application of peptides like OS-01 may extend to other areas of cosmetic health and potentially even internal organs.
Another interesting technology we can explore is single cell sequencing, which is being used to understand what happens in one single cell as this cell ages, creating a very clear map of the aging process. This allows us to come up with several interventions that can reverse that process.
The same goes for gene editing and CRISPR, which will allow us to deliver specific treatments to specific tissues.
There is so much that's happening. I think the overall view is that we will get to this point in which we have control of our biology and we control it in a way where we can prevent diseases and have more years in good health.
LB: This vision is something that motivates you very personally, and has for quite a long time. It's a passion that we share, including with our audience and the broader longevity movement
We're going to wrap things up here, and as we do, we always like to hear a bit about the practical things that you personally are doing now in your own longevity strategy.
We've got all these exciting technologies coming up, but at the same time, the fundamentals we already know and understand.
For example, we've heard you mention cardiovascular disease risk in your family. Give us a few examples of your own, as we call it, longevity strategy. What are you working on now?
Carolina Reis’ Longevity Strategy
CR: As you mentioned, I have a history of cardiovascular disease in my family, and knowing that and knowing all of the studies around on meat consumption and longevity - I reduced the consumption of meat, particularly red meat, in general. My diet is mostly vegetarian, I occasionally I eat fish.
I also take some supplements. I'm currently taking NMN, and I did biological age test, before I started and I am planing to do another one to see if this will impact on the biological age itself. I'm also doing some blood tests that I hope can help me see the effects of NMN.
Speaking of NMN… Our Founder Nick ran a self-experiment using NMN + Resveratrol. Why not take the chance to read about it here?
Another hack is fasting. I know that fasting is very good for you. I used to snack often and eat every three hours. Now I'm trying to eat fewer meals and fast more.
The hardest one, I would say, is trying to manage stress. Running a company is sometimes very challenging.
I know the impact of stress in our health and, I feel, on my skin, literally. So I'm focusing a lot on meditation to be able to navigate better those challenging times.
LB: Those are very valuable examples. Thank you so much for sharing those. We particularly like your example with NMN. Our Founder Nick also tested his biological age before and after initiating an NMN protocol and improved his biological age by three and a half years over 6 months.
Carolina - thank you so much for sitting down with us today and sharing all of the amazing things happening at OneSkin. With that we can close it off!
CR: Yeah, of course. Thanks for having me!
Before You Go!
Why not check-out Nick’s self experiment results from OS-01 and learn how to run your own!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
oneskin - targeting skin aging at the cellular level: An interview with CEO Dr Carolina Reis - Part 1
DOES ONESKIN OS-01 WORK?
Let’s face it (pun intended?), the beauty industry is riddled with unsubstantiated ‘anti aging’ claims.
It would be challenging to find an aspect of longevity more difficult to navigate than keeping your youthful appearance.
Yes this certainly does not stop most of us from trying. The question - ‘how do I look younger?’ and related variants regularly top the Google search results time and again.
At Longevity Blog, we’ve been very cautious about engaging with the skincare sector, as navigating the science versus claims in this space is fraught.
But with today’s interview guest, we are confident we’ve discovered a company well worth your interest: OneSkin.
Let’s take a closer look at why.
OneSkin: Not just another ‘anti-aging’ skincare product
Not content with the aforementioned status quo, our interview subject Dr Carolina Reis and her co-founders set out to create a very different kind of ‘skincare’ company when forming OneSkin.
One with a very different approach to tackling skin aging and invested in the rigorous science required to back up any newfound claims (which in the case of their team are quite impressive).
Differentiators run deep at OneSkin, with Dr. Reis going so far as to describe OneSkin as a ‘longevity company’ at its core.
This is of course right up our alley.
OneSkin Technology
Their flagship product, OneSkin OS-01 does appear to offer a fresh approach to tired claims - with perhaps an industry first truly ‘anti-aging’ approach to skincare.
This is because OS-01 works differently than any other skincare product you’d be familiar with.
“You use a topical supplement in the same way that you take a supplement to improve your organs, internally. But a topical supplement treats our largest organ – the skin”
In fact, it’s not even a skincare product - rather, it is a topical supplement - whose benefits may one day run much more than skin deep.
Rather than covering up the effects of aging (fillers, moisturisers, etc) or relying on removing layers of skin to make you ‘look younger’ (retinol, peels, etc), OS-01 helps your skin to actually stay younger.
How? We’ll be diving into the details in this interview series. But to understand the basics - you first need to know that “OS-01” gets its name from its principal ingredient - a previously undiscovered peptide.
Peptides are made up of amino acids and serve as the fundamental building blocks of protein. They are required by many processes in the body - in the case of OS-01, the function is in cellular repair.
Peptides are not new to the skincare industry. However, the approach used to discover the OS-01 peptide is. As are the results this particular peptide seems to realise in human skin.
OneSkin OS-01 - Aging Repair at the Cellular Level
OS-01 removing senescent cells (stained in blue). Image credit: OneSkin
This is because OS-1 has been shown to directly assist with skin repair at the cellular level, particularly in response to UV damage.
It does this by preventing the formation of and clearing senescent cells.
And why does that matter?
It brings us to the key point of differentiation between OneSkin OS-01 and most every other anti-aging skincare product.
Senescent cells are a directly involved in aging, and in many cases are known to be a cause of aging itself - particularly in the skin.
To go further into this topic, we always like to hear directly from source. So, let’s get onto our 1:1 interview with OneSkin CEO and Co-Founder, Dr Carolina Reis.
May 2023 Update
Our Founder Nick self-experimented with OS-01 FACE and had some very impressive results.
See his face before and after using high resolution facial scanning technology at 6 months and after 12 months!
OneSkin Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with OneSkin, we have a negotiated an industry leading 15% off coupon code for our readers.
Use the code longevityblog at checkout to save!
This interview was conducted in February 2022 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
OneSkin OS-01 has demonstrated some very impressive visual results. Here’s an example of a before & after showing dramatic improvement in a clinical setting.
What is a topical supplement?
Longevity Blog (LB):
We’d like to start by better understanding two concepts that your team uses. One is “topical supplement”.
Your team refers to OneSkin OS-01 as a topical supplement, not a beauty or skincare product, very interesting.
Secondly, this concept of “skinspan”, which sounds closely related to healthspan. These are new concepts to our readers- tell us about them.
Dr Carolina Reis (CR):
You use a topical supplement in the same way that you take a supplement to improve your organs, internally. But a topical supplement treats our largest organ – the skin. By treating your skin topically (“on top of”) with this supplement, you optimize the health of the skin.
So “topical supplement”, basically means a product that's designed to optimize the health of the skin.
Obviously, topically, because we want to act directly on the site where we want to see the improvements. Also a “supplement”, since the supplement definition reflects better what we envision for this product.
Namely, extending their health and the function of the skin, more than just acting as a cosmetic (improving only the appearance, focusing on the surface) while we target aging at the molecular level.
What is Skinspan?
LB: And skinspan?
CR: In the same way that we are researching longevity interventions in science in order to expand the healthspan, that's the time that we live in good health and free of diseases, skinspan is referring to the time that our skin is healthy and functional.
More than just looking to improve the appearance of the skin, we want to extend the time that your skin is healthy and functional.
The consequence of that is that your skin will look better. Our primary focus is on the health of the skin. That's why we like to use skinspan instead of other classic cosmetic terms.
Why does skin age?
LB: In previous interviews, you've often addressed the concept of “skin aging at the molecular level”. Now, that's interesting phrase - give us an example of how the skin ages at a molecular level.
At right, UV damage in our Founder Nick’s skin, as taken by a Visia scanner. Nick will be putting OS-01 to the test - be sure to subscribe to Longevity Blog updates to see the results!
August 2022 Update: Nick’s self-experiment results are in! Can you believe he looks 7 years younger??
CR: Aging happens at the molecular level. As we age, we observe many mechanisms in the body that stop working properly. One clear example is the accumulation of DNA mutations, which in the skin are primarily caused by sun damage.
When we are young, we have DNA repair enzymes that fix this damage. But as we get older, that system becomes deficient.
If we are able to make that system continue to work efficiently, we can avoid that accumulation of damage that can lead to a more broad dysfunction of the tissue.
OneSkin Replicates Aging in the Lab
LB: The concept of UV radiation being an environmental trigger for skin aging through damaging DNA, it brings us back around to one of the foundational pieces of work that OneSkin has done - replicating skin aging in the lab.
There's some really interesting details here – for example, your team uses actual human skin - we want to know more about this. Phrases such as “3D human skin equivalents”, or “human cell based platform” jump out at us. You're using these tools to study the aging process. Tell us more.
CR: In order to develop a product that reverses aging, we need first to understand how aging works. If we can have a model in the lab that can replicate the skin aging process, this will allow us to test interventions.
A core piece of OneSkin’s technology is their unique ability to create human skin equivalents in the lab - and use them to create highly effective products for the treatment of aging.
We are growing human skin in the lab with tissue engineering techniques that myself and my co founders brought from academia.
Human skin is made up two major layers - the dermis and the epidermis. We reconstruct both of these layers in the lab and then test products on that skin.
We use neonatal skin cells, as well as skin cells from donors in their 30s, 40s, 50s and 70s.
Using a proprietary “recipe”, we can grow these cells into skin layers and then put it together in a way that replicates the natural human skin.
OneSkin develops products using human skin
LB: And what do you do with these 3D skin equivalents after you build them? What advantage does this provide you in developing interventions?
CR: The beauty of this approach is that these models replicate human skin so well, that the results we obtain “in vitro” (in the lab using skin models), will be very similar to the results that were observed in the clinic (in actual human skin).
This enables a very successful translation from lab to clinic, increases the chances our product will perform well when people buy it.
Examples of human skin equivalents in the OneSkin lab for three different ages.
Most cosmetic companies that are testing “anti aging” products on human skin are using neonatal cells. Basically they're testing aging products in baby skin. This makes it very easy to see improvements, but those improvements don’t necessarily show up in aged skin.
LB: This leads directly into our next question – on the topic of human skin equivalents you have samples of cells from young through to aged skin – but you also work on actually “aging” human skin in the lab, namely with UV radiation.
Then you embark on a process of testing many different peptides, several hundreds to one thousand or on the human skin equivalent model. Tell us about this process.
Peptides, senescent cells and skin aging
CR: When we started searching for moleculse that would reverse skin aging, we had one hypothesis - that one of the main triggers of skin aging is the accumulation of damaged cells called senescent cells.
We partnered with a university in Brazil that was studying antimicrobial peptides to see if any of them could be effective in decreasing the amount of senescent cells in the skin.
We started with a library of 200 peptides and created random variations in the sequence of those peptides to generate a total of 800 peptides.
We tested these peptides on the aged skin model and measured which ones were most effective in reducing the amount of senescent cells and were not toxic to healthy cells. That’s how we discovered our main peptide OS-01.
LB: Let’s talk about this peptide.
We found one quote about this this peptide, that it “consistently showed the ability to decrease human cellular senescence caused by aging, ultraviolet light, and other genotoxic stress is by 25 to 50%”.
Translate that to something a bit simpler for our readers?
CR: Let's say that we start with a cell population that's completely healthy. We then we can “age” those cells by exposing them to UV radiation. If, after the insult (UV exposure) 50% of cells became senescent in a sample, the samples treated with the peptide would only have 25% of cells became senescent.
“Whenever you have an stressor, our peptide helps induce DNA repair enzymes.”
This is a 50% reduction in senescent cells total burden. That's one way that our peptide works.
Whenever you have a stressor, our peptide helps induce DNA repair enzymes. This makes it much less likely that cells accumulate damage and go into the senescence state. This means you maintain healthy skin function for longer.
Is OneSkin OS-01 a senolytic?
LB: That sounds like improved “skinspan”! This means that OS-01 one wouldn't strictly be considered a senolytic (a technology which removes senescent cells).
It is however, helping to avoid the buildup of senescence cells by promoting cellular repair. Is this correct?
CR: That is correct, but it's not the whole picture.
Our data supports that our peptide decreases both the production of inflammatory factors from the senescent cells but it also prevents healthy cells from becoming senescent even if they are in the presence of other senescent cells.
Because the main harm of senescent cells comes not from the senescence cells themselves, but more from the of inflammatory signaling that spoils the surrounding cells, causing them to age faster.
If we can block that communication, we can basically stop or decelerate aging.
Why are Senescent Cells Important in Skin Aging?
LB: Yes, you've talked about this in a couple other places. You've used the term “feed forward”. This is the concept of how senescent cells induce more senescence through inflammatory cytokines, creating a cascade of more accelerated aging.
How are we changing skin aging from “natural aging” once we introduce this peptide to our skin?
Fantastic results from longevity blogger VivaSparkle, where OneSkin OS-01 reduces the appearance of age spots, which are partly caused by senescent cells.
CR: Once you have senescence cells, there is a cascade of inflammatory signals leading to events such as collagen breakdown, which in turn will lead to a series of further dysfunctions in the skin.
These results in breaks in the skin barrier, and eventually, the signs of aging that we experience growing older, which are loss of firmness, wrinkles, dark spots, and so on.
If we're able to partially block the senescent cell feed forward loop, this allows the young and healthy cells to continue to proliferate, keeping up with healthy collagen and repairing your skin barrier, essentially reversing aging.
LB: This is getting back to one of the points you made at the beginning, which is the desire to create a skin product that doesn't simply cover up the effects of aging, but instead intervenes at one root cause of aging, which is cellular senescence.
There's a few ‘anti-aging’ skin products that are pretty popular that I'd like to get you to comment on. Retinoic acid/retinol and hyaluronic acid.
OneSkin OS-01 versus Retinol / Retinoic Acid
LB: Explain for us the difference between your OS-01 product and retinoic acid.
CR: Retinoids or retinoic acid work by peeling off the upper layers of your skin inducing a cell turnover. You grow a new layer of fresher skin, but not necessarily a younger skin. Your skin will look better, but this does not target what is driving aging at the cellular level.
From left to right, aged skin, and aged skin treated with OS-01 (notice epidermal thickening) and with retinoic acid. Image credit: OneSkin.
Using OS-01, you can promote skin rejuvenation in a more effective way - from the inside out, instead of the outside in and without the side effects of retinols (redness, dryness, skin sensitization and so on).
LB: The other ingredient that we just asked about was hyaluronic acid. This is included in your OS-01 product.
HA is a pretty useful tool in terms of skin health – so to our question: How do we know when we're using OS-01 that it's not the hyaluronic acid or other ingredients which are producing the results you claim? How people can be confident the benefits they are seeing are from the OS-01 peptide?
Does OneSkin OS-01 Work? Clinical Results
CR: When we ran our clinical study, we wanted to assess exactly that. We want to make sure that OS-01 is delivering more than our formulation.
Our clinical study was designed to be “split face”. So half of the face was treated only with the “basal” formula and half of the face with the formula plus the OS-01 peptide.
We assessed all the parameters after 6 weeks and 12 weeks. One of the most interesting results that we got from this study was an improvement in the skin barrier, which happened only on the side of the face that was treated with the OS-01 peptide.
In-vitro (in the lab on human skin equivalents), we conducted several tests in which we have treatment with the formula only and with the formula plus the OS-01 peptide.
We evaluated a series of genes known to activate or suppress skin health - genes related to aging, inflammation, collagen production, hydration, and so on.
Customer feedback: OneSkin OS-01 heals a stubborn eczema condition which steroid cream could not.
We then computed a skin score, combining the alterations observed in gene expression, in which a high score means a healthy skin, or the better for the skin.
The OS-01 peptide formulation always achieved the highest score compared with the formula without OS-1.
LB: Just to clarify, for the readers, what you're describing is that you've taken the formulation (the OS-01 product) and tested it with and without the OS-01 peptide and saw the above improvements only when the OS-01 peptide was included. This is how we know the OS-01 peptide is the primary active ingredient
COMING UP: Self-experimenting with OneSkin OS-01
LB: This leads us nicely into the topic of self experimentation. Give us some advice on how our readers can run a self experiment and come to the conclusion - “yes, OS-01 helped my skin grow younger”…
Read Interview - Part Two!
August 2022 Update: Nick’s OneSkin Self-Experiment Results are In!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Longevity: Fasting, Diet, Sleep, Stress - How to Personalise Your Approach
Longevity: Fasting, Diet, Sleep and Stress
Nick and Dr. Robert Lufkin MD dig into the ‘secrets’ of longevity. You can find the full video here.
Understanding how to positively influence your longevity is complicated and at times overwhelming!
Demystifying longevity and simplifying the steps you can take to make improvements to your healthspan (and someday soon, perhaps lifespan) is what Longevity Blog is all about!
Today, we hit upon three major topics in longevity - fasting, diet, sleep & stress in our with Dr Robert Lufkin, MD of Health Longevity Secrets.
How to Fast for Longevity
Fasting is one of the more recent major health trends. And like many health fads, it comes in hot and with plenty of miracle claims on how it cures all forms of ailments.
Analysing the benefits of fasting for your longevity and how you might approach fasting for longevity purposes is a challenging topic area with no ‘straight answer’.
Calorie Restriction and Longevity
Here’s what we know. Calorie restriction (eating slightly fewer calories than your body requires) over a lifetime improves healthspan and lifespan in many animal models, including rodents and even primates (who are closely related to humans).
However, there are no longitudinal studies on fasting which can demonstrate this is the case in humans.
Long-term strict calorie restriction has its advocates in the longevity health space. And quite a spritely bunch they are!
But to date, they are placing their bets on a very challenging type of fasting, which when done inappropriately can actually lead to early death (the opposite of what you want!) in some cases, and which has little to no robust scientific data specific to human longevity or lifespan.
Weight Management and Longevity
We love the fasting app Zero! It’s a great way to track your fasts and join a community of others looking out for their best health interests. Plus its totally free!
One thing that we do know for certain, is that eating too many calories (more than your activity level requires) over a long period of time is associated with many chronic health conditions.
Why? Because it leads to being overweight, even obese, and increases systemic inflammation.
It even increases your biological age.
If you want to improve your health outcomes, you should maintain a healthy weight.
Through the lens of longevity, this makes fasting is a valuable tool. One that can you can use to reduce your weight to a more optimal level & reduce age-related disease risk.
For some insights on the types of fasting you can use to accomplish this, checkout Nick’s discussion with Dr. Lufkin at ~33:40 (or the transcript below) in our YouTube interview!
Does sleep increase lifespan? How many years does lack of sleep take off your life?
Getting quality sleep is essential for your health and longevity. How much does sleep affect your healthspan? Well that depends!
It is well established that getting too little quality sleep is very bad for your health, while getting enough quality sleep helps your body heal/recover more effectively.
From a first principles standpoint - we can predict that getting enough quality sleep is certainly very important for your longevity.
How much sleep do you need?
However, the details behind this statement are difficult to pin down. Your personal needs cannot be explained to you in a generalised blog post.
You have to take this matter very much into your own hands, and become an expert in understanding how you sleep best.
Getting ‘enough good sleep’ breaks down into three major components:
Sleep duration (how much you are sleeping)
Sleep quality (how well you are sleeping)
Sleep schedule (how regular your bedtime/waking time are).
Improve your sleep by tracking sleep duration (how much you are sleeping), sleep quality (resting heart-rate, movement) and sleep schedule.
Once you have a baseline (4-6 weeks of data), start experimenting to see what can improve your numbers in these three categories.
How much sleep (duration) you need is very much an individual statistic. And your personal sleep requirements will change according to the demands of your day.
For example, athletes tend to need more sleep so their bodies can recover from their training. If they were to discontinue their intense training, they would need less sleep overall.
Meanwhile, shift workers who have irregular sleep schedules (e.g. nightshift work a few days/week) are known to have much higher age-related disease risks (e.g. cancer, cardiovascular disease).
How to Measure and Improve Your Sleep
Sleep quality has recently become more measurable, which allows you to monitor it over time and get a baseline for what ‘normal sleep’ looks like for you.
Jump ahead in our video interview to ~39:50 (or the transcript below) to hear from our Founder Nick on some tricks for using everyday wearables to establish your sleep quality and how to analyse what helps you sleep better (or worse!).
How Does Stress Affect Longevity / Life Expectancy?
We hear a lot about how damaging stress is to our health and longevity. So much so, it might even be stressing you out!
“Stress” however, is far too generic a term. For example, stress can be good, so long as it does not overwhelm the biological system. Nature has developed robust responses to stress to recover and then become more resilient against a specific stress.
You can self-experiment with stress, just by observing your emotions, feelings & thoughts. To do so, try mindfulness meditation to practice observing your mental state.
Once you build some basic skills, you’ll be able to better notice how the events of your day impact your mental health.
We’ll be bringing you some examples on how to track stress/anxiety and run a self-experiment in future posts.
What you should concern yourself more with is being able to 1) observe your mental health state and 2) identify what triggers poor mental health for you. From there, you experiment with positive changes to your lifestyle, supplement stack and mental adaptation strategies.
Starting with observing your mental health status, our Founder Nick recommends using mindfulness meditation.
Learning to sit with your thoughts, emotions and feelings creates an ability to observe them. Without practicing this, you’ll lack the all important skillset required to know what is stressing you out.
By building an ability to understand and observe your mental health state, you then become enabled do something about what brings on poor mental health and do something about it.
Using a mindful mind, you’ll be able to the self-reflection and self-observation required to become aware of what specific life events are causing you to feel stressed.
Nick is currently running a self-experiment to improve his anxiety levels, as informed by his personalised genetics report from Self-Decode.
From there, you can develop strategies specific to these triggers.
We’re in the progress of using Nick’s personal results from Self-Decode to explore our personalised stress and anxiety supplement recommendations from their platform, to demonstrate how you can do this effectively!
Tune into the YouTube interview to hear more from Nick on this topic, at ~43:40 (or read the transcript below!).
This is part two of our transcription of an October 2020 interview between Dr. Lufkin and our Founder Nick.
It is in excerpt format, to highlight key points of the discussion with basic edits made for purposes of clarity and correctness. Timestamps are approximate.
Is fasting good for longevity?
Robert Lufkin (RL) at 33:40
What about diet? Fasting, we hear so much stuff about that, and longevity, what's your what's your take on on that as as far as influencing longevity?
Nick Engerer (NE) at 34:02
Look, this is this is a fascinating discussion. And once again, when we start talking about diet, we start talking about fasting. We're really getting onto this question of what will work for you and you need to be able to measure before and after…
Fasting refers to many different types of restricting your diet, it might be calorie restriction, eating a fewer number of calories overall, it might be dietary restriction, removing a certain part of your diet. For example, keto diet, the ketogenic diet, it's an extreme example.
It might also be something where you change the times that you're eating, you might only eat in the evening, you might only for a few hours a day or maybe an eight hour window.
And then there's of course the true fast where you go for a few days at a time, with just some water and electrolytes, maybe a multivitamin
I've experimented with all of them. And so I've had to go through that self-experiment and learn for myself what works best for my biology, and do that through testing my bloods, looking at how I feel, what are my energy levels, what is my skin look like?
What Type of Fasting is Right for Your Longevity?
… Coming back to the point, somebody who is extremely overweight, maybe morbidly obese, and really needs to lose some weight - fasting is a powerful tool for that person, they should absolutely consider it … they might be able to go for extended periods of time and not eat and lose incredible amounts of weight
There might be just the average person who needs to lose 20 pounds, and they so they decide they're going to skip breakfast, eat in a smaller window, and make sure they're not overcompensating for missing breakfast by eating more calories at lunch and dinner.
Why Nick Doesn’t (Currently) Fast
… I mentioned earlier that I'm now a triathlete. So I wake up and eat and then I eat again and then I eat again, and then I eat again. And it's because I'm working out two times a day, to adapt my body to be more of an athletic one. I'm convinced that over a decadal timescale, the most important thing that my biology can have is better mitochondria, stronger muscles and adapted body with great angiogenesis and fresh blood vessels, circulating nutrients and clearing waste throughout my body.
There's all these benefits that I cite for why I'm doing this. Now, that means I'm not necessarily getting the benefits of restricting my calories, which we know does provide longevity benefits. Calorie restriction is one of the most powerful tools for actually improving lifespan outcome in primates. And we think that that applies to humans.
But that's not the only knob you can turn to improve your longevity. There's several - so you have to try to pick a longevity strategy and implement what you think's going to work best for you and your biology over the long-term, and put your cards on the table after you place your bets.
I'm going down the exercise route, I'll probably eat less as I get older overall, but now I'm finding that the eating small meals throughout the day is powering exercise, which is making my body stronger, my heart stronger, and leaving me feeling pretty fantastic.
RL at 38:11
What are the other knobs for longevity? We touched on exercise and diet. What other knobs can we turn there?
Using Blood Testing to Choose a Longevity Diet
NE at 38:25
When it comes down to thinking about your biological age there are four important things you can change, diet, exercise, stress and sleep.
We've just talked a bit about diet (fasting) - let me give a further example on how it can be personalised.
Nick’s blood lipids over time, with 3x different diets highlighted.
When I did the ketogenic diet for a year, my cholesterol levels were out of whack. My LDL-C was too high. My particle count for the lipoproteins was too high.
I looked at that data and said - “Look ketogenic diets, not the right thing for me”.
Instead I've come around to eating low amounts of saturated fat, pretty much eliminating dairy, and still eating red meats, fish, chickened balancing that out with eating a lot more plants
That diet has improved my inflammation levels and reduced my LDL-C and my ApoB number (representing the lipoprotein particles counts and their sizes). So that diet is a healthier thing for me.
But that's not necessarily the thing that will be right for everyone. So you have to back that up with blood testing, how you feel and your overall goals.
Eating a diversity of plants is one diet change Nick can back up with a self-experiment. Checkout the details here! You might find GlycanAge biological age tests to be valuable in your own diet optimisation! Use the code ‘longevityblog’ to save 15%!
Sleep and Longevity - What Nick is Tracking
Let’s talk about sleep next. And also, you've done some great experiments on NMN and some other things. If you want to talk about those that that would be interesting as well.
NE at 40:50
Okay, let me tell you what I think about sleep. Sleep is again, highly personalised, like all this stuff is. Some people will hit the hit the hay and just knock right out and sleep through the night. Good on them. I wish I was one of them. I'm not.
In fact, through analysing my own genome, I am in the the 98th percentile for insomnia! So I'm a bit of a thrasher!
I have to really think about my sleep and get on my A game. I've just pretty much eliminated alcohol altogether in my life. But more importantly, if I'm going to have a drink, it's going to be a day drink.
If I have a single beer or wine for dinner, I can already see resting heart rate increases my heart rate variability drops, and as a result I don't sleep as well for the first part of the night till my body clears that out of its system.
Same thing for eating meal too large of a meal late at night, I'll see elevated heart rate for a few hours before it finally comes down.
That increased heart-rate is reducing the amount of recovery that I get from my sleep.
It's fairly in vogue to do sleep tracking, I get a lot of data from the Oura ring. It's has its limitations. I wouldn't say I trust its sleep stage data very much.
But what it does tell me is it tells me how much I'm moving around. It tells me what my heart rate is and measures my heart rate variability, my body temperature.
Just looking at those metrics alone makes it possible to collect data and infer outcomes.
What about Sleep Supplements? Do they work?
I've also then been able to self-experiment with sleep stack supplements.
For example, I was just trying out valerian root. I thought I felt like I was sleeping better, but when I went back and looked at my data, I couldn't see any evidence of that. So I did not add it to my stack.
I've experimented with other sleep related supplements like magnesium L threonate, or Magtein, but that turned my brain on too much. One of the only things I found that works for me was magnesium glycinate. I'll take around 300-400mg as that seems to relax me a bit.
How to Interpret Your Sleep Data for Optimisation
… So for your own personalization, get a format for collecting data, the most important thing in my view, is being able to see movement and heart rate. Your heart rate should drop off fairly quickly and lower out into a nice plateau and then pick up when you wake up.
If you don't see that, if you see the heart rate staying up and you see it spiking throughout the night along with movement - these are signs that you're not sleeping as well as you could.
You can gather that information from a smartwatch. You can gather that stuff from a ring or a whoop band or any other mechanism you want. But being able to then take it and inform your personal longevity strategy is the most important part.
In my office rocking’ these blue light blocking glasses from DoNotAge. 10% off when you use the code ‘longevityblog’.
That means changing one thing at a time, collecting some data and deciding very objectively - did trying that thing improve my sleep yes or no? Do that over and over again until you know what works for you. That's how I would approach sleep.
One last thing - blue light blocking works for me in terms of sleep onset.
Particularly if you got a screen at night or you're in a bright environment. Light control is huge.
So I take all the blue light out of my environment I turn I got LEDs that light up my home and I turned them down to a warm tone and that turned them down to a red light as we're reading go to sleep in the house.
Controlling the lights is really, really important for sleep.
Stress and Longevity
How about stress then? Same type of thing?
NE at 45:05
Stress - we have a proclivity to it in modern society… I actually intentionally live out what we call in “the bush” in Australia - meaning I live in a rural area. Every time I go to the Big Smoke (Sydney), where my company is based and visit with my team, I'm amazed at just how many cars are trying to kill me, the noise that is in my ears, the pollution I'm breathing in, the light that's coming at me all times of the day…
Learning to understand that your body has having stress response to everyday activities… these things have impact on your subconscious and raise your stress level. Being able to notice what increases your stress level and what is causing you to have a stress response… is important to figure out in your in your own subjective awareness.
Meditation and Longevity - Become Aware of What is Stressing You
The most powerful tool for being able to notice this is mindfulness meditation. I've done a lot of meditating in my life. I've done a lot of self reflection, and meditation retreats - all that good stuff. Meditation has become a powerful tool, much like fasting, that I know when I need to use, and has also given me a baseline awareness to be able to see in my own mind, what I'm experiencing, what I'm thinking, what I'm feeling.
That's what you need to do in order to understand stress, because until you can take that step back and observe the things that are making you feel stressed, you won't know what to eliminate.
Once you can see that, then you need to eliminate and control. I'm actually doing a self-experiment with some of my personal results from Self-Decode, exploring the stress and anxiety supplements that have been recommended to me by my genetic reports
Self-experimenting with these supplements is important because the same thing won't work for everyone. A great example - CBD oil makes me feel anxious. I feel good for the first hour and then I feel anxious for the three hours after that. That's not the experience that most people have.
Developing the skills to figure that out for yourself by self experimenting, adding one thing at a time, keeping a journal … That's the way to approach managing stress.
So first - mindfulness to gain perspective, and then (second) try taking things away or adding things in (supplements) to control that stress more effectively.
RL at 47:38
I'm hearing the theme of personalization and being aware of your own body and what works for each of us. It's such an important important message.
What about supplements,? You mentioned a couple like resveratrol or NMN. Anything there you recommend?
…
This interview continues, covering Nick’s multiple self-experiments and his role as an Advisor to DoNotAge.
If you’d like to hear more, you You can watch the rest of this video interview between Dr. Robert Lufkin, MD and our Founder Nick here.
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This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
How to use biological age testing kits and build a personalised longevity strategy
What is my biological age?
Nick and Dr. Robert Lufkin MD dig into the ‘secrets’ of longevity. You can find the full video here.
Your biological age can be estimated through a number of different methods. We’ll discuss those in some detail in this post.
What this biological age value is attempting to answer is - how old are you really? Meaning, how old is your body at the cellular level?
Answering this question has only recently become possible.
But one of the challenges is - there are many ways to ‘measure’ it, and not all of them will give you the same answer!
More to the point - can these tests enhance my longevity strategy?
How Do You Measure Biological Age?
Biological age can be ‘measured’ by a blood test or a saliva sample.
Using these samples, certain aspects of the sample are analysed, depending on the test type:
Telomere length (looking at your chromosomes)
Phenotypic age (comparing a compilation of blood tests to your peers)
Epigenetic age (looking how your DNA is expressed by the epigenome)
GlycanAge (reviewing the signalling molecules for inflammation in the body)
How to Calculate Biological Age
This question brings us nicely to our interview subject matter today.
Calculating biological age from the above samples is based on the following process, with widely varying degrees of simplification:
Researchers gathering many thousands to hundreds of thousands of the above samples
Building a model based on the chronological age of the donors + the markers measured
Choosing the risk target of the model (e.g. all cause mortality is most common)
Using the model to review your sample to tell you how hold you ‘look’ compared to your peers, biologically
There are many commercial offerings for doing this, several of which we have reviewed in detail on Longevity Blog (read on for more!).
What Does A Biological Age Value Tell You?
Biological age and longevity is a complicated topic, and it is not easy to sort through marketing hype and make a clear decision on how you want to engage with this relatively new technology.
Thankfully, our friend and colleague Dr Robert Lufkin is looking to make sense of these messages and find the ‘secrets’ often buried in the details.
In his recently launched Health Longevity Secrets show, he’s delivering a new episode/podcast each week interviewing topic areas experts.
On episode 18, he interviewed our Founder Nick, covering a wide range of topics with a distinct focus on biological age (the focus of this post) and also fasting, sleep, stress and diet (the focus of part two of this interview).
We’re bringing you the highlights (hosted on YouTube) of the discussion in excerpt form, where the tables have turned and Longevity Blog the interview subject for a change!
This is a transcription of an October 2020 interview between Dr. Lufkin and our Founder Nick. It is in excerpt format, to highlight key points of the discussion with basic edits made for purposes of clarity and correctness. Timestamps are approximate.
Biological age testing and the Personalised longevity strategy
Robert Lufkin (RL) 1:18
Maybe just to start off - when did you know you wanted to focus on longevity? I mean, you're not that old right now. So what happened?
Nick Engerer (NE) 3:08
I'm 35, but I've always been interested in health as a hobby.. That came through for me in powerful way in my late 20s when I had three important people in my life get cancer in the same year, all in their late 20s.
One of those was my wife - diagnosed with appendix cancer 30 minutes after my son was born through Caesarean section.
Those encounters with mortality really got me thinking at a young age around what can we do to engage with this ever present risk that we have in the background … there's a lot of technologies around to enable proactive screening for health conditions of all types. There's a big trend going on now with proactive healthcare technologies being able to pick up diseases earlier and earlier.
The costs and barriers of those coming down further and further.. those two trends really caught my interest.
building a personalised longevity strategy to simplify complexity
RL at 5:34
We’re all about ‘Sticking Around’, and self-experimenting with the many ways of doing so. Like this self-experiment with NAD booster NMN!
The Longevity Blog, which I love! … I love the motto for it: “Stick around”. That’s good… I look forward to reading and every time
Stepping back, how do you view longevity? What is your concept of longevity?
NE at 6:05
I'm a scientist ... I come to this thinking with a scientific view. I find it really interesting that we have an increasing availability of ways to test and gather data on our own body, and then form a view of how we interact with our health and specifically our longevity with that information.
When I think about longevity as a problem space… there's simply so much that one can do. There's so many pathways… it's simply overwhelming to try to engage with all of them. It's not possible.
How do we really simplify that? I like to think about it in terms of developing a personalised strategy. We’re working to pull together content on Longevity Blog…
I'll give you a specific example about how to think about this…. We can do a number of different exercises to actually personalise your risk profile.
The most simple example is doing a family health questionnaire; what did your grandfather and your grandmother on both sides of your family - what age related diseases did they experience? What about your parents, aunts and uncles?
This is totally free… you can take your doctor and start a discussion. See ahead of time - there's early heart disease in my family, what am I going to do about that? Or there's early onset Alzheimer's in my family. What am I going to do about that?
This simplifies the problem space down to some first actions that you can start to take in targeted ways to engage…
Personalised Longevity Strategy - where to start?
RL at 9:14
That's such a good point Nick. It's one thing to talk about longevity and and do the rapamycin and the resveratrol but we all need to first look at our risk factors because we can boost our longevity …
Giving blood at NextHealth Los Angeles for a Micronutrient Test. Finding critically low micronutrients in his blood was a key part of informing Nick’s personalised longevity supplement regime.
You mentioned screening and labs … could you talk about how someone would put together that screening profile for themselves?
NE at 10:10
That’s part of my obsession - trying to figure this out. There's simply so many tools at our disposal that we need to start with that simplifying lens that brings the scope down.
I've played around with many different technologies, some of which are a few thousands of dollars, some of which are less than 100 bucks. I’m continually working to pull together examples of how to use these different tests, or different blood screens or biological age estimates to really formulate a way of creating self experiments that show what works for you.
But even that's a bit advanced. So how do we really bring this back to the basics? Moving beyond that family health questionnaire, the place that I'm increasingly looking to is genetics.
How Do Genetics Influence Longevity?
There's been a big spike in recent developments and the capability of analysing the genome… what's happening is that computational resources and machine learning and data science are coming together with genetic information that's being studied... coming together in a way where we can not just look at single parts of the genome, but look at hundreds of thousands to millions of parts of the genome and pull together a picture with that, using machine learning and data science approaches.
Self-Decode, a comprehensive genetic testing kit for less than $100USD. Use it to customise your longevity strategy by targeting your stack-building and lifestyle changes toward future age-related disease risk.
We just interviewed Joe Cohen (Founder at SelfDecode) on Longevity Blog… 60+ scientists and data machine learning data science folks who are really moving the needle on the capability of genetic analysis.
What they've been able to do with the advances in the science is personalise analysis and suggestions … now we can look at an individual and say… here are the specific diseases we can connect your risk to, for cardiovascular disease, or for neurodegenerative disease, or for metabolic disease. And these are the age related diseases.
Again, use it as a simplifying lens in the overwhelming space of all the things we can do… to work toward avoiding age related disease. And to start doing that 10 to 20 years ahead of time… you can start being proactive in changing your lifestyle in a specific way
Epigenetic Testing for Longevity (including Biological age)
RL at 15:04
Are you aware of any other companies that are looking at the epigenome for doing machine learning of the same thing with, you know, methylation clocks?
NE at 15:49
Yes. This is where things are going now. Epigenetic understanding in science has really accelerated over the last five years, again, because of the ability to sequence and be able to do that types of real in depth analysis to pull the data out of the epigenome which is changing over time, which is responding to the environment.
...That space is a bit behind, you could say it's 10 years behind genome sequencing, and that we're still connecting what's happening in the genome to outcomes.
I've spoken with the CSO of Chronomics Dani Martin-Herranz, which is one of the leading companies in epigenetic analysis … we get a biological age number, but how do we know.. what we should do to improve that biological age?
Order your own epigenetic biological age test from DoNotAge. This kit includes customised insights into gut, vision and cardiac health. Use the code “longevityblog” to save 10%
The fact is that the data is not there yet, the science isn't there yet to say this is what the epigenome is showing us.
This is what you need to change to be more youthful or to solve a given problem…it's a even thornier problem than simple genetic analysis, but it will increasingly inform us on our health journey, particularly our longevity journey, as it's becoming central to understanding some of the ageing process itself.
what can biological age tell us about longevity?
RL at 18:36
Dr. Morgan Levine and some of the others from Yale and other places - they're finding that depending on what you train it on, the clock is going to be biassed towards cardiovascular risk or dementia risk or other risks like that.
NE at 20:15
I can add a few things there - Dr. Levine… I've watched several of her lectures, they've done some great collaboration with National University of Singapore talking about biological age clocks… what's happening biological age clocks is trying to express risks in the mortality space over time [to] represent your risk for a disease outcome.
That [biological age] number at the end is nice for a consumer because it's an easy story. But what's more interesting to me and where I think we're going to future is increasing dissection of those results to give useful information.
[Checkout 3x FREE ways to estimate your biological age!]
You mentioned Gordan Lauc from GlycanAge - we’ve interviewed him on Longevity Blog .. I actually just successfully improved my GlycanAge, it was our I'm 35, it was 30, I got it to be 24. I did this by eating a diversity of plants in my diet...
Nick improved his biological age by 6 years through a change in diet. How? By eating 30+ different plants per week. Checkout the details here!
Being able to use these tools to improve a biological age result does seem to suggest an improved health outcome.
But what's really interesting about the GlycanAge product is they actually break it down into three indices… you can actually look at these indices and see where you improved by trying an intervention.
… When you start to break down that result beyond just an age, you start to see, okay, I've increased my performance by reducing the number of inflammatory glycans in my body, which are causing chronic inflammation, and increasing the number of good glycans in my body, what you're saying to the rest of the body is systemically toned down inflammation… that's better for your longevity.
Reversing Aging versus Improving Biological Age
RL at 24:07
The question is if we reverse DNA methylation, have we reversed our risk of ageing?
NE at 24:47
This is important to get this out there for the consumer. There's a lot of different biological age tests. They will give you a result that comes out of a model that is trained that has some value.
If you get a number that says you're 40 years old, and you're 50, you're biologically younger on that metric, which is probably better than your peer who is 50, but gets a biological age of 60. There's some merit to the absolute value here.
But what's more interesting to me, and I've talked to Professor Lauc at GlycanAge about this, is that changing our biological age, the relative value… [getting a] lower value is indicative of making a positive health change wherever that model is trained.
Want to go deep on biological age models? Checkout our technical interview with Deep Longevity CLO Alex Zhavoronkov.
For glycans, the overall inflammation in your body. We're not talking about a single marker like C reactive protein, homocysteine… we're talking about 24 different glycans that track and tag the individual molecules in the body to tell the immune system what to do, before any of those blood markers go up.
The consumer needs to know what they’re trying to change based on which biological age test they’re using and what it represents. Then the should try to implement a positive change to that number, and testing again, some months later.
They also need to know how long that marker takes to change. With GlycanAge, you can change in just three months. With an epigenetic age test, it might take 6 to 12 months. So understanding the science and tech behind the biological age tool that you're going to use is part of what we demonstrate on Longevity Blog.
… One other thing I'll add - don't get caught up in calling it “reversing” ageing … No, you have improved your mortality risk because that age has gone lower. That's a great thing. But we're not at a point where we can “reverse” true biological age, in terms of turning that number down with interventions.
… The point is we have a couple new metrics that we can use to run self experiments and improve the longevity outcomes for our body, which is fantastic.
Biological Age in Athletes: Exercise and Longevity
RL at 28:31
One promising longevity molecule Urolithin A is making a big impact in the athelete work. Supplement “Mitopure” is demonstrating improvement in endurance performance through enhancing mitophagy (the death of defective mitochondria). Read more in our interview with Amazentis CMO Federico Luna.
That's a great point... I wanted to get what's your take on biological clocks measured in extreme athletes, they've noticed shortening of their age (increased biological age). Have you encountered that at all?
NE at 29:12
Yes. In fact, GlycanAge is a great example of this.... I am convinced far and away the best, the most powerful longevity drug you can take right now is exercise.
Now, exercise is an interesting drug, in that its doses are widely varying, and they're highly personalised. I recently did a deep dive on exercise and its profound benefits for longevity, and I decided that I wanted to really up my fitness game, and I actually became a triathlete.
So now I'm training for triathlons. And it's been a huge change for my body. I've seen so many positive things that have resulted from that. But I know that ... there's a so called J shaped curve, which is well known in the sports medicine industry. Once you exercise too much, you start increasing your risk, particularly for health conditions like atrial fibrillation
...There's risks that athletes face because when it comes down to a real true athlete, these individuals are pushing their body so hard day after day after day… exercise produces a profound amount of damage and inflammation in the body that the body that needs to recover to become stronger.
Over time, continuing to push your body really, really hard, like a professional athlete does, isn't actually probably good for longevity… I don't know where the bottom of that curve is, but it somewhere around 450 intensity minutes of exercise a week, according to big cohort studies.
So there's, you can do a lot of exercise. And you should, because it's a really good drug and it keeps improving your health outcomes. But professional athletes are on the far end of that. And this is why we see, you know, decreased benefit to high levels of really intense exercise, it's just simply too hard on the body for it to recover all the way.
RL at 33:19
Well, now that we're talking about some lifestyle things like exercising.. What about diet? Fasting, we hear so much stuff about that and longevity. What's your take on fasting influencing longevity?
Longevity Strategies for Fasting, Diet, Sleep and Stress - Read More in Part 2!
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Genetic Risk Analysis for Longevity: An Interview with Self-Decode Founder Joe Cohen
Do Genetics Determine Longevity?
The simple answer is ‘No’. Genetics do not determine longevity.
Longevity is a determined by a multitude of factors, including your environment, socio-economic status, risk appetite and of course diet, sleep & exercise.
However, they do very much influence longevity.
And when it comes to your personal longevity strategy - the simple answer of ‘No it’s not genetics that will determine your lifespan’ misses this key point.
Perhaps most importantly, noting that genetics do not determine longevity ignores a very important point. Namely that in planning ahead for a long and healthy future - you as an individual are not a statistic.
So, How Much Do Genetics Affect Longevity?
Genetics could have a lot to say about your longevity as an individual in many cases.
We can point to several illustrations.
Do you carry the APOE4 gene that significantly increases risk for Alzheimers? What about the BRCA genetic variants that influence breast cancer (as well prostate cancer)?
What about Lp(a)? Do you carry the genes which lead to elevated levels of this nasty little lipoprotein? If so, your risk of heart attack at a young age is significantly elevated.
To answer the question, ‘do genetics affect (influence) longevity?’ - you need to look past the mainstream articles written to appeal to a wide audience.
They are borne from high level statistical analysis.
Does it it really matter to you what the genetics of countless others determine on average?
Of course not. As an individual it matters what YOUR genes say. And if you carry any of the genes we just mentioned, you’re at elevated risk of early onset age-related diseases.
That means genes could very much influence your longevity in a significant way.
What to do about it? Read on.
What Genetic Factors Determine Longevity?
Once again, searching the internet for this answer will bring you to a bulleted list of ‘major’ genetic factors that may influence healthspan and lifespan.
Big deal! Eye roll.
Why? Because these articles once again miss the point - you need to zoom in on your individual genetic risk profile to know what risk factors you carry.
Thankfully, on this personalised assessment front, there is welcome news.
Progress in genetic testing and genetic analytics has moved incredibly quickly over the past decade.
Perhaps most importantly these advancements have been in both cost (genetic sequencing is getting cheaper) and importantly the algorithms that can connect scientific studies about specific genetic variants to disease risk.
And not just any old risk - your risk.
These technological advancements are now able to get quite specific about that.
Let’s talk about ‘the how’.
How reliable is genetic testing in predicting disease risk?
If you haven’t been paying close attention to this space, your knowledge on the topic is likely quite dated.
The answer this this question, just a few years ago was bleak - simply put, genetic testing was not very good predicting disease risk.
However, the rate of innovation with genetic analysis has been particularly quick over the past few years, and through technologies like artificial intelligence, it’s picking up the pace.
Self-Decode’s DNA test kit is mind-bogglingly cheap, at only $90. We’ll learn how they use an advanced machine learning process call ‘imputation’ to analyse your genome in a very targeted way, to keep costs down, while delivering a very deep analysis.
If we want to understand how reliable genetic testing can be for assessing disease risk (and thereby your longevity) we need to get past the dated & mainstream and up to the front of the pack.
Onward, to the forefront of genetic analytics!
This takes us to the exceptionally impressive data science, genetics and science team at Self-Decode.
They have recently developed some remarkable capabilities for genetic testing (low cost & accurate) and analytics (years ahead of the competition).
Most importantly, they’ve also built a successful platform for delivering personalised insights about your longevity risks AND what you can do about your risks.
How have they done it? We’re glad you asked…
Next Generation Genetic Analytics: An Interview with Self-Decode Founder Joe Cohen
In order to better understand Self-Decode’s mission and the capabilities of their team, we interviewed their Founder and CEO Joe Cohen.
Joe Cohen is the Founder and CEO at Self-Decode. He is an avid biohacker and self-experimenter, as well as a respected entrepreneur.
You may be aware of Joe’s earlier work on the website ‘Self-Hacked’, which is one of the most widely used and thoroughly cited biohacking websites on the internet.
When we interviewed Joe, asking specifically questions about longevity and genetics, we were very impressed with the capabilities they’d developed.
Perhaps most interesting was Joe’s announcement of the arrival of a ‘2nd generation’ of genetic analytics.
This 2nd generation is powered by artificial intelligence and advanced data science, which has recently become capable of providing a level of insight health enthusiasts, biohackers and longevity junkies (like you) have been left wanting to date.
Namely - what should I be doing to manage my personalised risk?
Personalised Genetics Insights with Actionable Information? Finally!
As we said at the opening - simply put, early stage genetic analytics have been fairly disappointing.
Direct to consumer genetic analytics really hasn’t really proven all that useful for the everyday wellness warrior and longevity enthusiast.
However, at Longevity Blog, we believe we are entering a new era of test at home genetic kits.
We’ll help highlight why this is the case through our discussion with Joe and in upcoming posts which dive into Self-Decode’s online genetics reporting and analysis platform.
When we’re through, we expect you’ll feel confident that Self-Decode genetic reports can become part of your personalised longevity strategy.
We’ll also take a look at their LabTestAnalyzer platform, including insights from a self-experiment run by our Founder Nick to radically reduce his LDL-C cholesterol levels.
Let’s get onto that interview!
This interview was conducted over Zoom during August 2021. It has been edited for brevity, conciseness and correctness.
Longevity Blog (LB): Joe, to kick things off, tell us about SelfDecode, its mission and purpose as a company, and what is your team's united behind? What's your mission?
Joe Cohen (JC): Our mission is to improve people's health. That's really what it comes down to in a very small nutshell. The real question is: what is the best way to do that? We think it is through personalized health strategies, looking at DNA and lab tests, and giving more precise recommendations.
One defining aspect of Self-Decode is the incredible scientific & data engineering team they’ve built. With 85 people in the company nearly 70 are dedicated to making their genetic testing & analytics better every day! Meet the team here.
LB: A core part of the offering from SelfDecode is genetic testing. In several recent interviews, you've been discussing the arrival of ‘a second generation of genetic analytics’.
In these interviews you specifically discussed the involvement of artificial intelligence. Introduce us this ‘second generation’ concept - in particular, how SelfDecode’s offering differs from other apparently similar services.
JC: Most companies that are doing genomics are not actually doing personalised health. Actually, none of them are, really. In order to do the analysis right, it takes a lot of very specialized skills that are hard to come by.
Very few companies are actually doing this and no B2C (direct to consumer) companies are doing genetic analysis correctly. 23andMe may be one company that's doing the analysis correctly, but they're not giving precision health recommendations.
In order to do genetic analysis correctly, you need to look at millions of variants. Whereas most companies are only looking at a handful of variants, and then making conclusions based on that.
Number one is they're not doing the analysis correctly. Number two is not giving precision health recommendations.
In order to do these both well, you do need to use AI and deal with large amounts of data. That's a big computational challenge and a major reason why companies are not doing this.
Single Nucleotide Polymorphisms
“In order to do genetic analysis correctly, you need to look at millions of variants.”
LB: One of these challenges and points of contrast is the analysis of single nucleotide polymorphisms, or SNPs, and the limitations of looking at individual SNPs.
Second generation analytics is looking at much more than a single SNP - it is instead looking at many, many points in the genome. Can you explain how that's important for creating that personalised guidance you're describing?
JC: First, looking at many points is more important for genetic risk for a disease. If you're only looking at one SNP - it's like looking at one letter in a book, right? Not even one word, just one letter.
Single Nucleotide Polymorphisms refer to a single location in the genome which may vary from individual to individual. Most genetics analysis test kits look at single SNPs to provide limited insight.
Self-Decode is different. They look at many thousands to millions of SNPs to provide you with personalised guidance.
Sometimes if you look at a few key variants, you might be able to spell a whole word, and that may give you some insights. But more or less, looking at a few letters and coming up with broad conclusions means you’re missing tons of information.
The future of genetics is with AI. But using AI means you need to build an entire data analysis pipeline to look at the holistic picture for risk.
Then after that, if you want to provide personalized information, you can use labs and environmental risks to get a more of a whole picture. That's what Self-Decode does.
Combining Genetic Analytics with Blood Tests
LB: In terms of that actionable, personalised guidance, you have just mentioned analyzing labs in conjunction with genetic risk factors. Your platform then goes on to recommend supplements and lifestyle changes based on those results. Could you provide an overview on how that works?
JC: Users can upload lab results that they get from a doctor using our LabTestAnalyzer and then receive information about the optimal ranges for each blood marker. We then provide recommendations on how to get these markers into the normal or the optimal ranges.
We're working on combining the labs, the environment and genetics in order to create a more holistic picture about what is going on in the individual. And then provide them with the best recommendations to get them into being optimally healthy.
Self-Decode’s Deep Scientific Expertise
“We have a team of 85 people with about 65 to 70 in the science, engineering and development space”
LB: One of the things that SelfDecode has accomplished which is quite unique in this space is assembling a very capable and diverse team of scientists, engineers and software developers to do this type of work. Can you tell us a little bit about your team? What does this team look like? What are they doing?
JC: We have a team of 85 people with about 65 to 70 in the science, engineering and development space. We need a large data engineering team, because we are dealing with lots of data. We also have bioinformatics scientists and genomic scientists, as well as software developers who have to become familiar with these topics.
Our team of software developers, over a couple years, have become more like ‘genomics developers’ really. Many of the data scientists are experts in machine learning and AI.
LB: That team sounds quite diverse and capable. This depth and diversity is one of the reasons Self-Decode has come out with such a high quality product.
Innovating on Genetic Testing Kit Price
Self-Decodes’s genetic test kit is far and way the best value for this market category.
Through the process of ‘imputation’ to scale up your genetic sample, they can offer a low price kit ($100USD) with the equivalent deep dive genetic analysis of kits which are many times more expensive ($500-$1000USD).
LB: One thing we’d like to ask you about is the cost. The price point for entry is pretty attractive, at around only $100.
Using your genetic testing kit, you’re able to directly test on the order of 700 - 800,000 points in the genome. But then you use some fancy AI techniques to scale this up to 83 million locations.
This process of ‘imputation’ is used to fill out the genomic data with a high level of accuracy. Explain this process to our readers.
JC: We have an imputations team that are working on creating more accurate predictions of SNPs not directly sampled.
We use AI to predict based on the patterns that we see. There are actually pretty good prediction methods for this that enable us to predict 83 million SNPs from the 700,000, which is basically all the snips that you have with 99.7% accuracy.
LB: Using this imputation process, you’re able to produce some impressive level of detailed recommendations.
That team, the algorithms and the product have enabled SelfDecode to move beyond a simple genetic risk score style approach (typical for the genetic testing industry) and onto specifically guiding users on what disease risks will be present for them in the future and how they can minimise those risks.
Genetic Reports with Personalised Guidance
Self-Decode’s Cardiovascular Disease Report can reveal much about your risk factors for developing cardiovascular disease.
LB: You present this information to the user in a series of customised reports, each dedicated to a specific category. Could you walk us through some specific aspects of your reports?
In particular, our audience is very interested in longevity. You have reports on cardiovascular disease and cancer, as well as diabetes and metabolic disease. Tell us more.
JC: We have a bunch of different topics. And you know, topics like cardiovascular disease are very important for longevity. Blood sugar is very important for longevity. Every report looks at a different number of variants - usually around 1 million.
Then we also have to look at your ancestry as well, that's something that we're working on. We have an entire team that's working on ancestry, because your ethnicity plays a very big role in your risk.
For example, if a study is done on a Japanese population, it may not have applicability to you (if you’re not of Asian descent). A study done on a different ethnicity doesn't have a good chance of being applicable to you.
The report then gives a prioritized list of recommendations that change based on your genetics. So we do a very deep dive into the interactions between genes and specific health recommendations. We also give the supporting evidence behind those recommendations - everything's referenced.
LB: Take for example your cardiovascular disease risk report, it reviews different types of cardiovascular disease risk from strokes to vascular complications to congestive heart failure.
The report, using the genetic information we just discussed, then provides specific personalised guidance for the use. One thing we love about these recommendations is that they go beyond the typical “exercise and eat well” guidance and get much more specific.
For example, the cardiovascular report for our Founder Nick recommended quercetin and calcium supplementation.
Personalised recommendation delivered to our Founder Nick after he ran his cardiovascular disease report on Self-Decode.
Self-Decode Delivers Priority Ranked Personalised Recommendations
LB: What can users expect when they complete the genomic testing kit and access their reports. We assume that the recommendations are different for everyone?
Self-Decode have a dedicated longevity report which details personalised risks in the aging process. You can review it here.
JC: Yes. These are priority listed, meaning the top recommendations go up and down the list based on an individual's genetics.
LB: Right - that's the real winner there, a key differentiator. It is personalised guidance, we like that!
One of the reports is actually dedicated to longevity specifically. It reports a personalized risk profile for oxidative stress, inflammation, cardiovascular disease, and DNA repair.
For users interested in assessing risks to their longevity and optimising their healthspan, how can the Self-Decode platform help them optimise? What do you think, Joe?
JC: I would certainly look at the recommendations in the longevity report and then implement those recommendations. They're a bit different with everyone.
Joe’s Personal Longevity Strategy
LB: In terms of thinking further about this topic of risk and longevity and using Self-Decode, let’s talk a bit more about your own health optimisation journey.
Your original work was on the website Self-Hacked, before going on to found SelfDecode, and was largely inspired by your own personal biohacking journey. Share with us how the Self-Decode platform helps you make decisions on your own personal longevity and wellness optimization?
JC: The platform is quite useful to explore the many different topics I am interested in. I'll look at the report recommendations, and then I'll look at which genes are involved. Then I go ahead and try out the recommendations. Every report can be used to add new things to your personal health regimen.
I also look at my labs (on Lab Test Analyzer). For example, if I have high blood sugar genetic risks, I look at my labs and track that. The same can be done with high cardiovascular risk, where I look at triglycerides, HDL and LDL.
“The more you are learning about aging, your health - you’re just going to be more healthy”
Some things are for longevity, and then there's things for more the short term. For example, the mood report. That's a big thing I'm looking at. What are the things that I could do to improve my mood? I’ll take the report recommendations and start implementing them.
It gives me more motivation to continue with my personal journey.
LB: Could you share a specific example? Perhaps a specific example of something that you were recommended where you tried it and it helped?
Joe’s Self-Decode Mood Report steered him toward 5-HTP. A great example of how personalised guidance can improved overall wellness more effectively than flying blind.
JC: Definitely. 5-HTP was a big thing for mood, because of the various serotonin genes. And that came up on my reports, and I implemented that, it had a positive impact and so I have been taking it ever since.
LB: This type of wellness feedback loop is one of the things we think your platform is most powerful for.
As we wrap up the interview, let’s talk a bit more about you. We ask all of our interviewees to share part of their own personal longevity strategy.
What is your strategy for maintaining your health in your 60s, 70s and beyond?
To Be Healthier, Make Learning about Health Your Hobby
JC: For me, it is very much about the motivation to be healthy. It’s like exercise. Everybody knows they should exercise, but not everybody does it as much as they need. I think you need to find motivation to do it.
This is where health education comes in. For example, like reading about your health - the more you are learning about aging, your health - you're just going to be more healthy. If you're reading health articles, reading your genetic reports, tracking your results - you're just going to be more healthy, because you're into it.
The other big thing is knowing what to do. Many people are lost, and they don't know where to start. What's the best thing for them? It's important to approach where that starting point is. Disease screening and the report recommendations give you something specific to try out and see which one works the best for you.
There's still some of that self experimentation. But our reports give you the things that you should be trying first.
LB: That's a great answer, Joe. We love that you hit on those longevity topics.
Thank you so much for your time today, Joe, we really appreciate you coming to tell us about SelfDecode. We think it's a fantastic platform for health optimization, and your answer about making health a hobby - SelfDecode enables that directly.
Thanks again Joe!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
NMN Transporter Slc12a8 and the future of NMN clinical trials with Dr Alessia Grozio
The need for NMN Clinical trials
In a recent post, we discussed a key barrier in our knowledge of NMN supplementation in humans - namely the very limited clinical trial data.
However, this barrier is soon to be removed, thanks to high profile research + business collaborations which a directly confronting this lack of information.
Dr Alessia Grozio is Chief Scientist at Elevant and a researcher at the Buck Institute, ‘insanely’ interested in all things NMN and longevity.
With their execution and success, we will soon have a clear understanding of the benefits of NMN supplementation in human subjects (well beyond simpler experimental results, such as how NMN improved our Founder Nick’s biological age by 3.5 years).
Collaborations on NMN Clinical Research
One such collaboration we recently highlighted was the the work between aging research leader the Buck Institute, Elevant, and its parent company Seneque.
Together they have developed a healthy pipeline of NMN clinical trials in humans, which will focus on muscle recovery after exercise, potential benefits to skin health and much more (details in our interview).
Today, we host Elevant’s Chief Scientist and Buck Institute Researcher Dr. Alessia Grozio (PhD) for an exclusive interview on the future clinical trial outlook for NMN.
Interview with NMN researcher and expert Dr Alessia Grozio
Longevity Blog contacted Dr. Grozio with a number of important questions on the topic of NMN supplementation in humans.
Seneque’s mission is to increase healthspan by 20% in the next decade.
One key topic area we addressed was Dr Grozio’s co-discovery of a transporter that delivers NMN directly into cells called slc12a8.
This discovery was the first time that a pathway for NMN to enter cells directly had been discovered. A key development which well renowned NMN expert Dr. David Sinclair was very quick to highlight in Nature Metabolism (read it here) .
This discovery has not been without controversy, as NAD biologist and researcher Dr. Charles Brenner was quick to criticise the study. This has led to a bit of a schism in the research community on whether or not slc12a8 does what Dr Grozio says it does.
So we wanted to hear it from the expert directly, asking Dr. Grozio to help us better understand the significance of slc12a8, particularly around how NMN enters the cell (which is critical for it to fulfil its NAD boosting function).
As always, we also ask her about her personal longevity strategy.
Without further delay - onwards!
This interview was conducted in written format over email correspondence during May 2021
Longevity Blog (LB): Dr Grozio, thanks for joining us here on Longevity Blog.
To kick us off - you work diligently at both a research organisation and a commercial venture. Surely its hard work! Tell us - what drives you? What brings you into work each day?
Alessia Grozio (AG): Thanks for inviting me. The passion for my work and an “insane” curiosity for anything related to aging/longevity and NAD+ biology that brings me to work every day.
After earning my PhD in biochemistry, I started working on the enzymes (sirtuins, NAMPT, CD38/CD73 ecto-enzymes) involved in NAD+ metabolism.
NAD biology is quite complex. This is an area Dr. Grozio finds quite fascinating. We do too!
In a previous post with Dr Grozio’s college, Dr. Eric Verdin, we discuss this topics in further detail.
I have always been fascinated by the pivotal role that NAD+ plays in maintaining homeostasis in our body and the plethora of cellular processes in which it is involved.
Therefore, investigating the effects of NMN (nicotinamide mononucleotide), a critical endogenous compound for NAD+ biosynthesis, in different physio-pathological conditions where NAD+ levels are impaired, was a natural prosecution of my scientific interests.
More than “hard”, I would say that my job, as for many other scientists, is never boring!
What is NMN-C
LB: Thank you for sharing those personal insights. One of the reasons we’re speaking with you today is to help introduce ‘Elevant’, and your efforts to make ‘NMN-C’ available to a broad audience.
Please introduce us to NMN-C. How does this formulation differ from other forms of NMN that our readership may already be taking?
“What makes our NMN-C special is the extremely high level of safety and development that has gone into it. ”
AG: What makes our NMN-C special is the extremely high level of safety and development that has gone into it. We think what is most important is providing consumers with NMN-based products that have the highest levels of safety and quality possible.
NMN-C is exclusively available through Elevant in their “Prime” product (pictured)
What’s critical is, once NMN has been synthetized, to characterize the impurities, filter them as much as possible to reduce them to the minimum, and make sure that the few impurities remaining are safe.
In our NMN-C the level of impurities is very low, complying with the pharmaceutical grade guidelines.
Our product is then tested at high dosage, pre-clinically and in human, to confirm it’s safe to use.
Is NMN Safe for Humans?
LB: There was a recent study specifically looking into the ‘safe’ level of NMN supplementation, could you share some information on this work?
“NMN-C at doses up to 1500 mg/kg/d appears to be safe”
AG: Our NMN-C acquired self-affirmed GRAS (Generally Recognized as Safe) status in accordance with US FDA regulatory guidelines, performed by an independent panel of toxicology and nutrition experts.
Moreover, we have recently published the first OECD 408 toxicology study performed on NMN. This study analyses the No Observable Adverse Effect Level (NOAEL) of our NMN-C and demonstrated that repeated oral administration of NMN-C at doses up to 1500 mg/kg/d appears to be safe and did not promote adverse effects in rats up to 90 days.
Diagram showing the role of Slc12a8 and how it enables NMN to enter the cell. Source: Nature Metabolism
Does NMN enter the cell intact?
LB: You made some waves in the research community with your published results on a NMN ‘transporter’ slc12a8.
This was a particularly exciting discovery, as the ‘doorway’ for NMN to enter the cell was previously unknown.
Could you briefly explain why this discovery is significant for the prospects of NMN supplementation?
AG: The identification of a novel NMN transporter, Slc12a8, further advances our knowledge regarding NAD+ metabolism by providing a new mechanistic insight through which the absorption and distribution of NMN is regulated to fuel the NAD+ biosynthesis in different tissue.
In the manuscript published in 2019 in Nature Metabolism, we employed several biochemical and in vivo (testing done in a whole organism) analyses to demonstrate that the Slc12a8 gene encodes a selective NMN transporter that facilitates the direct uptake of NMN into cells and intestinal tissue of mice.
We found that Slc12a8 is regulated by NAD+, specifically, Slc12a8 expression is increased when intracellular NAD+ levels are declined, as a compensatory mechanism, in order to maintain the cellular NAD+ homeostasis.
The Debate Around Slc12a8
LB: Proponents of alternative NAD precursors (NAD biologist Dr. Charles Brenner amongst them) such a Nicotinamide Riboside have contested that slc12a8 is an ‘intestinal cation-calcium transporter’ and not an NMN transporter.
The NMN proponents predicted that NMN would still work as NMN in cells that don't have NR kinase but we and others showed that when NR kinase is knocked out, NMN can only raise NAD+ by acting as nicotinamide. That's because NMN works by conversion to NR and needs NR kinase /14
— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020
Surely the ‘devil in the details’, but what is your reply to such claims?
How can we trust that NMN is making it ‘into the cell’ intact, rather than only through the Nicotinamide Riboside Kinase pathway as NR?
AG: Slc12a8 is an orphan member of the SLC12 family of the electroneutral cation–chloride co-transporters, this means that so far, its function as cation–chloride co-transporter has not been demonstrated.
Indeed, Slc12a8 shares low level of similarity with its family members for what concerns amino acid sequence and predicted membrane topology.
As described in our Nature Metabolism paper, we have conducted isotopic tracing experiments using side by side isotopic NMN and nicotinamide riboside in Slc12a8-OE NIH3T3 cells (the cell line overexpressing Slc12a8 protein) and primary hepatocytes from Slc12a8 knockout mice (mice completely lacking the Slc12a8 protein).
Both experimental conditions demonstrate direct NMN uptake without any previous conversion of NMN to nicotinamide riboside outside of cells.
LB: Thanks for answering that very important question.
NMN as a Topical Cream for Skin Health
LB: Moving on from transporters, and onto Elevant’s impressive research efforts, you are engaging with some very significant topic areas - namely beauty and sports performance, which are very significant consumer markets.
Could you share with us the future of NMN based ‘creams’ for topical use? Is this a future development area for beauty products? And do we know if NMN can enter skin cells through a topical? (We are very interested in measuring & preserving aesthetic age)
AG: Yes, previous research has shown that NAD+ appears to play an enormous potential role in skin health.
Research has shown that NAD+ energizes aging skin cells to function more like young cells, counters transepidermal water loss and improves the moisture content of the outer layer of the skin, along with several other actions that support healthy skin.
We have conducted clinical trials that have directly shown the beneficial effects of NMN on the skin.
The trials demonstrated improved skin moisturization, elasticity and brightness, and a reduction in skin roughness and visibility of wrinkles. The results are to be published soon and we will share them with you.
NMN for Exercise Recovery
Longevity Blog is very interested in how anti-aging compounds might improve athletic performance and the benefits of exercise.
Another longevity supplement “Urolithin A”, which is derived from pomegranates, also has benefits on improving physical recovery, through the mitophagy pathway. Read more!
LB: An ongoing clinical trial is now recruiting participants, which will analyse the benefits of NMN for ‘physical capacity and recovery’.
Looking forward, do you see a potential future role for NMN in human performance (i.e. sport)? If so, do you have any insights on how it might improve an athlete’s ability to compete in their sport of choice?
AG: We have preliminary results showing NMN is efficient on physical recovery, at any age. We will keep you informed, prior to the publication of our results.
Upcoming NMN Clinical Trials
LB: Beyond these two clinical trial areas, Seneque are also ‘preparing’ several more clinical trials covering many areas with NMN-C: impact on NAD+ levels, NMN vs NR, sleep, cognitive function, immunity - each is a significant undertaking (self-titled ‘the world largest pipeline’).
What timeline do you expect for the results on these projects? They will each go quite a long ways toward demonstrating the efficacy of NMN supplementation.
Seneque has a very impressive pipeline of NMN based clinical trials at various stages of maturity. Find the latest on their website.
AG: Two more studies started this month (May 2021), a tolerance and a pharmacokinetic study with 20 participants each and dosage of 400mg per day. Preliminary results to be announced next July (2022).
The first results of further trials will be published Q3 2021 and several publications will occur until July 2022. You can see our extensive clinical research pipeline here.
Some additional confidential studies are being conducted at the moment, so pending the timing and results of those we hope to start communicating about them at the end of this year.
We are confident it won’t be long until we can demonstrate the efficacy of NMN supplementation in several clinical trials.
We aim to be able to share results sometime between Q3 and Q4 2021.
Research Business Partnerships for Longevity Research
“We are confident it won’t be long until we can demonstrate the efficacy of NMN supplementation in several clinical trials”
LB: Some elements of these clinical trial efforts will occur in partnership with the Buck Institute, namely the pre-clinical studies and basic research efforts.
Could you describe the merits/value of private longevity technology companies collaborating with leading aging research institutions? What are the challenges for you personally, ‘wearing two hats, so to speak (as you’re also a scientist at the Buck Institute)?
AG: The main interest in collaborating with leading aging research institutions is to work and share knowledge with scientists coming from various backgrounds and expertise, foster new ideas and drive our research to constantly innovate.
This allows diverse new research leads and areas of study, all undertaken in line with scientific principles.
The powerful and high-end equipment and infrastructure at the Buck is of course a huge asset.
Finally, as you know, time is of the essence. These partnerships allow invaluable gains of time.
NMN-C is Manufactured to a High Standard
LB: Elevant is now manufacturing NMN-C in Europe, which differentiates from other suppliers of NMN, who rely on manufacturing in China. This undoubtedly introduces additional costs, but likely as a trade-off for many benefits.
Could you comment on what ‘Made in Europe’ means for consumers?
AG: We strictly control every element of our proprietary manufacturing process, which we undertake at cGMP-certified facilities in France. Consumers receive what we believe are pharmaceutical grade and the highest levels of quality and safety available in an NAD+ booster today.
Dr Grozio’s Longevity Strategy
LB: Dr Grozio, changing gears, as we close off the interview - could you share with our audience one or two items from your personal longevity strategy?
AG: I am Italian, therefore I am following a Mediterranean diet, rich in vegetables, legumes, fish and extra virgin olive oil.
Moreover, I am taking our NMN-C every morning to boost my physical and mental energy needed to go throughout the entire day.
LB: Dr. Grozio, thank you such much for taking the time to answer our equations today!
Want more NMN Focused Content? We got it!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
How GlycanAge Biological Age Testing Works - An Interview with Glycan Expert Gordan Lauc
Glycans Can Be Used to Estimate Biological Age
In our most recent post, we explored the basics behind biological age testing with glycans.
Working up from the basics (what are glycans?) through to how glycans interact with inflammation in the body, and ultimately are a signal of the aging process itself.
We also heard from Nikolina Lauc, CEO at GlycanAge, a longevity technology company based in the United Kingdom, whose mission is to “bring glycoscience into the hands of both clinicians and consumers to inform, guide and preserve your future health”.
GlycanAge has recently made it possible to purchase a direct to consumer kit to assess your ‘glycome’, which as we will learn in this follow-up post, is a powerful indicator of your future health and longevity.
Today, we’re publishing an exclusive interview with glycan expert and GlycanAge Director Gordan Lauc.
Gordan is not just a glycan expert, he is THE global authority on all things glycans.
As a Professor of Biochemistry and Molecular Biology at the University of Zagreb, he kicked off the Human Glycome Project in 2017 and has built the world’s largest human glycome database.
Through this effort, he has built an entire research team who have pioneered the glycomic analysis technology required to inspect glycans quickly and efficiently.
It is this technology which has made consumer testing of biological age and personal health status through glycans possible.
Our interview subject, and global glycan leader, Professor Gordan Lauc.
While an impressive figure of great reputation, Gordan is also a great conversationalist, amateur gardener and all around collaborative and friendly bloke who is passionate about helping people lead healthier lives.
Through collaboration with GlycanAge, we sat down with Gordan for a 1-on-1 interview, diving into the details behind how the human glycome works, and how to use it to assess biological age.
We even documented Gordan’s input on how you can run your own self-experiment with GlycanAge, to improve your health and overall longevity.
Let’s get into it!
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This interview was conducted on 20 May 2021, over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Screen capture from Gordan’s YouTube video where he briefly tours his state of the art glycan laboratory.
How does the GlycanAge test work?
Longevity Blog (LB): Gordan. We recently checked out a video that is uploaded to YouTube. It was from an Instagram Live video with longevity doctor. Dr Joseph Raffaele.
In this video, you briefly toured your glycan laboratory. We found that absolutely fascinating.
You had a few generations of machines that were in place, and it made us naturally quite curious.
Could you explain what happens when a GlycanAge sample comes into your lab?
Tell us about the process of going from blood sample to glycan analysis!
Gordan Lauc (GL): Glycans are very complicated molecules. You cannot just read the letters in the way you read DNA or protein, they're branched. They're chemically very similar, but in the same way very diverse. Analyzing glycans is a challenge. This is why we need so many fancy machines.
When we do the GlycanAge test, it focuses on the glycan immunoglobulins. First, we have to fish out immunoglobulins (IGG) from the blood sample (a dried blood stain collected by fingerprick),
We have a special technology to get just IGG out of all other proteins in the sample. From the IGG, we remove the glycans, using a special enzyme which acts like a pair of scissors. It removes the one group of glycans called N glycans from the IGG.
After this, we have to dye them to make them visible in our machines. These machines use capillary electrophoresis, or chromatography, which separates glycans based on their chemical structure. Then we quantify the amount of each of them.
For the GlycanAge, we focus on glycans which change with age.
LB: There's around 2,000 to 3,000 types of glycans, is that right?
GL: When we talk about the total 'glycome', there are approximately 2000 different glycan blocks. For IGG, there are 24 major structures, so this “fishing out” process of the immunoglobulin reduces the number of glycans significantly. Using these individual structures we calculate the changes which happen with age.
Biological Aging and Glycan Immunoglobulins
Pictured: A 3D model of an human immunoglobulin
LB: In this biological age analysis, there is a close link between the IGG N glycans you're analysing as age markers and inflammation.
Can you can you explain that connection between these immunoglobulins and inflammation in the body.
GL: Immunoglobulins are the main weapons of our immune system. They are made to recognize any foreign object (bacteria, virus food, any foreign molecules) which comes into the body. They do this by a relatively complex genetic process to make a hypervariable domain to bind to this foreign object.
LB: A complex process certainly - give us the simplified explanation.
GL: When antibodies are developed, they do not know whether a given foreign object will be an enemy, like a bacteria or a virus, or if it is friendly, such as food or a dust or something else they should ignore.
After the antibody binds to this foreign object, what happens next is determined by glycans. This very complicated process (glycosylation) is regulated by least 40 different genes. These glycans decide whether antibody will kill a target cell (activate inflammation) or will it suppress inflammation.
Inflammation and Glycans
LB: And it is this increasing level of inflammation across the body which is tied to aging. What does a youthful version of this process look like?
GL: What we see in young people is that the majority of immunoglobulins have these anti inflammatory glycans. But when there is an attack by a foreign invader, like a bacteria or virus, then you need inflammation.
The problem is that as we live longer. We are genetically not made to live over 40. Once you stop making children, your genes don't work for you anymore, they work against you!
As we're getting older, this process gets disturbed, and immunoglobulins become more and more pro inflammatory. And actually, what we are measuring in the GlycaAge test are these molecules which regulate inflammation.
GlycanAge Biological Age Estimate
LB: This is how you can produce a biological age estimate, right? If you know what the glycome of an old person would look like versus a young one, you can make a prediction. Talk about how you create a biological age assessment using this information?
Pictured: A GlycanAge biological age testing kit. We discussed some of the basics on these kits in a recent post.
GL: Initially when we developed the DNA typing, we noticed that glycans correlate with age. At the time, we were thinking to use this information to determine the age of a person who left a blood stain at a crime scene.
This is relevant information for police investigation, whether this was a young guy or experienced criminal.
We tried to correlate the glycans with chronological age, and this was reasonably successful.
When we did this, approximately a decade ago, this was one of the most accurate ways to determine the chronological age of a person. Subsequently methylation test was developed, which was way more accurate in predicting chronological age.
LB: But there is still unique value in the GlycanAge test, particularly in assessing lifestyle factors?
GL: What we have learned is that our test deviates from the chronological age, approximately nine years. But not in a random way! But in a way which associates with lifestyle.
On our GlycanAge test, people living healthy lifestyle will always be younger, while people living an unhealthy lifestyle will be older. Also, people with different diseases will generally look older too.
What is Biological Age?
GL: We realized that the GlycanAge is not a good test of chronological age, so we can't use it in forensics, but it is very informative about something we call biological age. Although biological age is a very tricky word, because there is no golden standard.
Learn more about assessing your biological age in our interview with Chronomics CSO Dani
There is no universal unit of measure of biological age. And so someone can give you any kind of number and you cannot say whether it's right or wrong.
LB: Let us ask you about that, Gordan. What do you think about this term biological age? Is “age” the right term? Or is it more of a “biological score” or a “health score”?
Why do you think the industry has chosen the term “biological age”? It sounds nice. But we’re hearing from you that that term is a bit squishy.
What Health Information Does GlycanAge Provide?
An example of the ‘indices’ for the G0 (top) and G2 (bottom) IGG glycans. A GlycanAge test gives you access to this information as well as your biological age.
GL: When we do research, we report 24 directly measured glycans and maybe additional 50 different scores.
But the problem is that this is too complicated for people to understand. So then we made two levels of simplification.
One level is that we have three key indexes or scores, which is G0, G2, and GS.
G0 are glycans without galactose, which are the most proinflammatory.
G2 are glycans with two galactoses, which are suppressing inflammation.
GS are glycans with sialic acid, which also suppress inflammation.
LB: These three indices are reported to users when they complete the GlycanAge test.
This ‘first level’ of simplification provides direct insight into the levels of inflammation driven by or suppressed by each group.
How are these indices useful for the user?
GL: These three indexes are something which one can use to quantify three different aspects of regulation of inflammation. These three indices are exactly measured from the blood sample. This means, anybody in the world who has the right equipment can take the same blood sample and they should get the similar number.
LB: From there, biological age is the next level of simplification?
GL: The ultimate simplification is the biological age, but that's just the name, you can also call it a score. This is the model number. It is not a number which has an absolute meaning.
Screenshot from one of Gordan’s presentations on the GlycanAge biological age clock. Source: YouTube and also this pubmed article.
However, we know that the higher biological age number means more inflammatory glycans, and that means more low grade chronic inflammation.
This chronic inflammation is something which happens with aging and with disease. A smaller number of the GlycanAge means more immune suppressive glycans, less low grade chronic inflammation.
This is a number which is modeled. We use 1000s of people (over 150k) to build a model and compare an individual to this model to determine their GlycanAge.
Of course, it's not absolutely “accurate”, because there is no golden standard of accuracy. But what makes GlycanAge different from other indexes of biological age, which are being used is that we know that glycans which we measure are functional effectors of inflammation. They're molecules which do the damage.
Improving Your GlycanAge Biological Age
LB: Gordan - let's talk about improving our biological age. In other interviews, we've heard you talk about four key factors: sleep, diet, exercise, and managing stress. Making postiive changes in these lifestyle can help change the glycan based biological age estimate.
Can you can you explain why that's the case? Why are those four factors driving the GlycanAge?
GL: These four factors are the key factors of healthy life. Now, we all know, we need enough sleep, we need healthy diet, we need a moderate amount of exercise, and we don't need too much stress. There is no magic in that.
The problem is that this is extremely difficult. We cannot do it all. It simply is not possible in a modern society.
Could GlycanAge testing help identify the most optimal diet for YOU?
The other important thing is that we are all very different. The more research we do, we are learning this.
For example, we did recently cohort of 1000 people on five different diets. And each diet is good for somebody and bad for somebody else, so there is no universal diet, which will help everybody.
LB: Fascinating! Could you share what some of those diets were?
GL: This is still unpublished. I cannot go into details. This was a large European project. But these diets were generally high and low protein and high and low glycemic index and different combinations.
High glycemic index is not bad for some people. It is bad for perhaps most people, but some people cope with glucose better than others.
What we are hoping that the GlycanAge can do is help people to focus on one of the four aspects which is dominant in them.
Gordan is actively collaborating with Dr Joseph Raffaele to explore using GlycanAge on his patients at his longevity clinic in New York. Image Source: LinkedIn
For example, for some people, it could be only a few extra hours of sleep, and then they don't have to spend an hour day in a gym.
For other people, it could be just less carbohydrates. And then maybe they don't have to sleep that much.
GlycanAge is a kind of objective tool to evaluate what works and what does not work for us.
You earlier mentioned this Instagram Live video Dr Raffaele and I did. He has an anti aging clinic in New York where they are testing these ideas.
GlycanAge and Hormone Optimisation
LB: Let's talk about that. Dr Raffaele specifically talks about hormone optimisation.
We know that there's a real strong relationship between hormone balance in women, for example, and menopause and perimenopause.
Research with GlycanAge is finding a close link in aging and hormone levels. You also just mentioned diet.
So here’s our next question: How do we create understanding on what an individual needs in terms of their own personalised approach to improving their GlycanAge?
GL: This is exactly what we're trying to do at the moment. We started to work with Joseph to test his patients, and they all turned out younger. His average patient is 20 years younger, for male and I think 15 for a female patient, which is unbelievable.
Estrogen levels change significantly over the course of a woman’s life. GlycanAge is closely correlated with these changes.
I asked him - what are you doing to your patients? What are you giving to them? He's giving them more or less everything one can do.
We decided to dissect what works in which patient, and are now trying to do proper, placebo controlled randomized trials to see which of the approaches work.
What we know is that estrogen is a very dominant factor in woman.
We had, we got samples from one very interesting study where menopause was chemically induced in young women. In a half of the group, the estrogen was returned with estrogen patch, and the other half of the woman received a placebo.
Estrogen supplementation completely prevented the change in the IGG glycome while the woman who were on placebo aged nine years in a few months on average. Some women going through menopause age as much as 20 - 30 years within a year (on average, this number is only 7-9 years)
This loss of estrogen is extremely strong regulator of IGG glycosylation. The problem is when these women lose their good glycans, its promoting low grade chronic inflammation.
We know for example, from animal models that this is causative of hypertension. The increased risk of cardiovascular diseases known to occur with menopause could be partly caused by the wrong balance in IGG glycans.
LB: Clearly the estrogen balance and associated with changes that occur in menopause are very important for aging in women.
What about hormone levels in men? Is it a drop in testosterone which drives the changes?
GL: Interestingly in men it is also estrogen which regulates IGG glycosylation. In the same study, they also had a group of men where the gonadal hormones were blocked. When the testosterone was returned, it saved the glycome from changing.
Pictured: Testosterone, which plays a secondary role in GlycanAge. It is the change in conversion of testosterone into estrogen, which is altered in ageing in men.
But if the testosterone was added back in combination with another drug which is blocking conversion of testosterone to estrogen, this (the glycome remaining stable) the protective effect did not happen.
So in men, it's not testosterone which regulates IGG glycosylation - it's estrogen.
Hormones are very important regulators. But it's not only hormones, and it does not work to the same extent, in everybody.
So we definitely need to do more research to understand it.
Self-Experimenting with GlycanAge
LB: Hormone optimisation is clearly a really interesting topic area. Here, you've highlighted how it works for women, how it could work for men in the estrogen sense, which is fascinating.
Let’s talk about isolating specific changes one could make using GlycanAge test results. On Longevity Blog, we focus on helping our readers conduct self experiments to find out what works for them.
Want to see an example of using GlycanAge to try to improve your biological age? Our Founder Nick is kicking off his own self-experiment, and wants to take you along for the journey. Subscribe to content notifications to learn how to do this yourself!
For GlycanAge, what does this process look like? Could you point to a successful model for testing and improving your GlycanAge in a way that you can say, I know what did improved it, it was _____ ?
GL: One good example is weight loss. Losing extra weight helps the vast majority of people, because obesity is a big driver of inflammation.
However, when trying to lose weight, people often make a mistake. I personally did the same mistake when I realised my GlycanAge was not ideal. I decided to sweat it out. I was hiking in mountains, three, four hours a day, for the whole summer.
While some aspects of my health did improve, my GlycanAge did not improve much. This is because overtraining is also causing inflammation. Usually people think more is better, but for physical activity, it is not!
What is a “Good” GlycanAge Result?
LB: How can users of the GlycanAge test use that information to strike the right balance?
GL: There is no magic coach who will tell you what to do. Even the best coach can only know what is good for an average person. But there is no average person in the world! We're all different.
Pictured: Our Founder Nick’s GlycanAge from April 2021. This is a ‘good’ age for him, as it is 5 years younger than his chronological age.
He will of course be trying to get it even lower!
What people have seen with our tests, and this is what makes me happy, is that, often they get a poor GlycanAge result.
At first, they're angry, they claim the test is not good. This is why we also offer a free consultation with some of our nutrition and lifestyle experts to help them identify the problem.
Soon, they find the problem.
Maybe I'm overworked. Maybe I'm not sleeping enough. Maybe it is too much stress, I have family issues.
But when people resolve these problems, GlycanAge improves! This is a fantastic motivator.
You know you did something right when you turn out now 5-10 years younger on the scale.
Elevated GlycanAge and Disease Risk
LB: And as you mentioned before, that reduced GlycanAge comes with reduced disease risk and many other health benefits.
“This is the process I like to see - when people get the bad result, improve and get a better result”
GL: Pro-inflammatory markers usually change up to decade before people become ill. Disease onset is usually like this - you work normally, live your life and at one point you feel pain.
Because of that pain, you go to the hospital, and then you do all the checkups. Then the doctor says - you have inflammation in your guts, this is Crohn's disease, or you have inflammation in your joints, this is arthritis.
This is the end stage, when all the compensatory mechanisms have failed. All the ways your body tried to fix the problem have failed, then you have pain, and then you get the disease.
The problem with most of these chronic diseases, they are irreversible. This is why we call them chronic, you get some medicine, you feel better, you don't have the pain anymore, but you are stuck to these medicines for the rest of your life or the disease returns.
But if you identity and fix inflammation early, often simple lifestyle changes or an early pharmacological intervention can prevent disease.
This is the process I like to see - when people get the bad result, improve and get a better result.
“Approximately half of the GlycanAge is determined by your genes, you cannot fix it. ”
Something which is not so satisfactory for the user is when they are already good. Because then they ask - “what should I do now?” I say nothing, you're good. Just come in a year or two and do it again to see whether you're still good.
LB: What is “good” Gordan? Is it 5 years younger? 10 years younger? Exactly your age?
How does somebody know that they're doing “good”? What says - keep going, stay the course, this lifestyle approach is working for you?
GL: Anything which is younger than your chronological age, I would say it's good. It’s also important to not worry about the absolute number, because the absolute number is also strongly affected by genetics. Approximately 30-50% of the GlycanAge is determined by your genes, you cannot fix it.
It is the relative number, the pace of changes in biological age which are important. If your GlycanAge is increasing more slowly than your chronological age, then that’s good.
I recommend starting to do this relatively early, maybe even at 20 to 30 years old, initially once every few years. Maybe if you make a change in lifestyle, then you do it every few months to see whether something works or not. This is the most informative.
How Often Should You Test Your GlycanAge?
LB: Talk about that part. If one of our readers takes a GlycanAge test, and runs a self-experiment, they’ll be thinking about how to control the experiment. Here, the shorter the time-period, the more likely they are to keep it well controlled.
What is the timescale on which our GlycanAge is changing? Is it 3 months? 6 months? Does it depend on what one is changing? Give us a sense for how often we could retest if we wanted to say test, reducing our stress, for example, or changing our diet.
GL: Glycans change relatively slowly. The half life of IGG is approximately three weeks. I think the shortest period to see something would be maybe a month. But this is for a really radical change. If you start taking a drug, or really changed lifestyle factors a lot, such as completely changing diet, starting to exercise much more.
Normally, we see things changing after three or four months. If you slightly change your diet today, it first takes some some time to manifest in the glycans. Normally, we recommend people when they change a lifestyle, re-test after three months and then six months again. If what you are doing is working, you will see the result.
LB: That's a very clear answer. Thank you. We didn't find a good answer for this out there, and our readers are quite curious!
GlycanAge and the future of longevity?
LB: We are going to move toward the close here.
What do you think the role of testing glycans and GlycanAge is going to be as we transition into a future where more of these interventions are possible to slow, halt or possibly reverse our biological age? Where is the GlycanAge test going to fit in the next five to 10 years?
GL: I think the GlycanAge will be one of the tools to evaluate different types of therapies and interventions. It will also not be the only one. GlycanAge is primarily measuring the pro and anti inflammatory arms of the immune system, and there are many other aspects of aging.
If you’re interested in biohacking your biological age - so are we. We recently published results on using NAD booster NMN for improving you biological age
For example, cellular aging is something completely different. Something that happens within a cell, like telomeres or energy metabolism (NAD boosters) and so on.
GlycanAge is looking at the organism as a whole. I think this will be a very good tool for people to just monitor the way they are consuming their body.
In a reasonable timeframe, this will become a regular medical test, like testing the HbA1c for diabetes. We will soon be testing the IGG glycans for a low grade chronic inflammation as part of inflammaging.
Gordan’s Personal Longevity Journey with GlycanAge
LB: In your own personal longevity journey, you you've openly shared that you've tested you GlycanAge fairly frequently. You’ve learned that you go through phases, right?
For example, stress increases when there is extra work to be done, you start enjoying food a bit more and it worsens. However, then you get on to a new training regime or new diet, and your GlycanAge improves.
“Even now I’m losing weight again, and my GlycanAge is going down again. It’s a marathon. It’s not a sprint”
Is regular GlycanAge testing almost encouraging you to lead a more healthy lifestyle for your personally? Is that accurate to say?
GL: Definitely it's an indicator, which helped me to identify some of the problems I had. I don't have a magic solution for myself, my GlycanAge is still not ideal. But I have learned that my key problem is food. I like to eat too much, I should eat less.
So yes, when it GlycanAge gets too high, then I am motivated to fix it. For example, even now I'm losing weight again, and my GlycanAge is going down again. It's a marathon. It's not a sprint.
How Can You Use GlycanAge Testing?
LB: And what would you say as a closing statement for others who are out there in that same up and down? Those who are really trying to make a health lifestyle change and curious to test their GlycanAge?
What is the takeaway from your personal journey that you’d take the chance to share with them?
GL: I think the most important value in the GlycanAge test is it gives us opportunity to focus on the changes which are effective for us, because there is no standard human. For me, I have that I can occasionally have that extra cake. The cakes are not that bad for me. It's more the fruit which is not so good for me.
GlycanAge can help you customise your longevity strategy. Should you walk more? Sleep more? Eat less?
Not everything which is considered to be “healthy”, is healthy for you. So the key thing we can get from the GlycanAge test, is information about ourselves.
It's revealing the hidden secrets of our body, which we can modify, which we can change.
This allows you to see what works and what does not work for you. So whether we are going to live 50, 70, 90, 120 or 150, it doesn't really matter.
What matters is that for longest we live, we should be healthy and enjoy our lives and not suffering from different type of pain or diseases.
LB: That's a lovely place to close that off Gordan, and thank you so much for chatting with Longevity Blog today.
GL: My pleasure! Thank you for your time.
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
NMN-C, Elevant and the future of NAD boosters: An Interview with Dr Eric Verdin
NAD Precursor NMN-C - A New NMN Supplement
As we have discussed in recent posts on NAD boosters, clinical trial data for NMN in humans remains quite limited.
In fact, up until recently, it wasn’t even well established that NMN was safe to use as a supplement. Hence, why we’ve had to discuss this issue and how minimise any risks in involved should you choose to self-experiment with NMN.
One key outstanding question has been - is NMN safe to take as a supplement?
IS NMN SAFE?
Excitingly, this question has now been answered, thanks to innovative work by the company ‘Elevant’ (in collaboration with two other parties, more on this shortly), who recently published results from a toxicology study for NMN supplementation (read it here).
On the back of this successful study, Elevant is now offering this a novel form of NMN, matching that which was used in the research effort - the product is called ‘Prime’, and the specific NMN formulation is called NMN-C.
What is NMN-C?
NMN-C is differentiated by its quality and extremely high-level of safety where the processes for characterising and removing as many potential impurities has been standardised and follows pharmaceutical grade guidelines.
Elevant’s NMN-C product, “Prime”
There are not any changes to the molecular structure, rather NMN-C is the outcome of this highly rigorous processing approach.
This outcome of this method for producing NMN has then been tested at high dosages (i.e. the study we just mentioned) and also in pre-clinical testing in humans.
This has made NMN-C the only form of NMN to be categorised by the US Food and Drug Administration as “Generally Recognised as Safe” - so called GRAS status.
Elevant, Seneque and the Buck Institute
These recent efforts to create and study NMN-C are the fruits of an exciting trifecta of collaboration between Elevant, its parent company Seneque and the Buck Institute.
They have an exciting pipeline of future NMN related studies in humans, including skin health, muscle recovery and more. We’ll explore these topics in an upcoming post with Elevant’s Chief Scientist.
Together, these companies boast some very grand visions, which should get any longevity enthusiast (that’s you) quite excited.
The Buck Institute for Research on Aging is a global leader in the study of aging, and increasingly, interventions in age-related disease.
Seneque, the parent company of Elevant, is a Swiss life sciences company, founded by French entrepreneur Guillaume Bermond, who now leads the company on its mission to “increase healthspan by 20% in the next decade”.
Rounding out the three-way collaboration is the Buck Institute for Research on Aging, who are global leaders in the study of aging, whose missions is equally grand - “to end the threat of age-related disease for this and future generations”.
Interview with Longevity Pioneer Dr Eric Verdin
Playing a key cross-over role between these three entities, is Dr Eric Verdin, CEO and President of the Buck Institute, and more recently, Chair of the Scientific Advisory Board at both Seneque and Elevant.
Longevity Blog reached out to Dr. Verdin to discuss this new role as at Seneque, and in order to better gauge his view on the promise of NMN supplementation in humans.
We discuss the use of NMN in human subjects, the role of inflammation and CD38 in NAD biology, the future of NAD boosters and even his personal longevity strategy.
This interview was conducted in written format over email correspondence during May 2021
Does NMN actually work? Is NMN effective?
Longevity Blog (LB): Clinical trial data for NMN supplementation in humans is at a very early stage, and we’ve yet to see conclusive results. Yet, the new venture Seneque will deliver NMN based products. What gives you confidence in the efficacy of NMN supplementation in humans?
Dr. Eric Verdin (EV): That’s a great question. I think that one should know that not everything from mouse or from animal model experimentation will actually translate into humans, and so there is always some degree of uncertainty in terms of what will happen.
Most NMN research has been performed in rodents, what will this mean for humans? Image credit
However, there is now growing evidence that NMN supplementation in animal models really has profound effects in the biology of every organism on which we have tested it. Based on this, one can be reasonably optimistic that we’re going to be seeing the same thing in humans.
One key thing that we will have to consider is the dose at which we give the NMN. Right now, NMN is typically commercially available at lower concentrations than what we’ve given to animals, and eventually we will have to account for some of the potential differences.
“NMN supplementation in animal models really has profound effects in the biology of every organism on which we have tested it”
CD38 Inhibitors for NAD Boosting?
LB: One of the more recent discoveries related to NMN supplementation, is a need to pay attention to the role of the CD38 enzyme. The Buck Institute recently published a study on the role of inflammation and macrophages in CD38 regulation. Could you comment on the potential role of CD38 ‘inhibitors’ alongside NMN supplementation? What compounds might prove useful in this role?
EV: Yes. What this paper actually showed is that, as we age, the activity of this enzyme called CD38 increases. CD38 is an NAD hydrolase, and so it is able to take NAD and to cleave it into its byproducts – ADP-ribose and nicotinamide – and we think that it is one of the major pathways that leads the progressive degradation of NAD that occurs during aging.
Longevity Blog did a deep dive on CD38’s role in NAD biology with Nuchido Founder Dr. Nichola Conlon - be sure to check it out!
So, on this basis, one hypothesis would be that to restore or maintain NAD levels in aging, we have to inhibit CD38, but you also have to replenish depleted NAD levels.
This is where NMN could come in. One thing to also consider is that CD38 also cleaves NMN, so this makes it even more of an important potential synergy between providing inhibitors of CD38 and providing NMN.
I think this is one way to move forward into the future – to have specific CD38 inhibitors and also to provide NMN to restore NAD levels.
“one hypothesis would be that to restore or maintain NAD levels in aging, we have to inhibit CD38”
Chronic Inflammation: CD38 and Senescent Cells
LB: As a follow-up, given the role of chronic inflammation and senescent cell activity (SASP) to create pressure on NAD levels in the cell, does this suggest that senolytic compounds (e.g. fisetin, quercetin, etc) may be a natural partner in boosting cellular NAD levels in addition to NMN?
EV: That’s a very good question. In the paper you discussed just before, which we published last December in Nature Metabolism, we identified the mechanism for the progressive increase in CD38 during aging, and one of the mechanisms was the progressive accumulation of senescent cells.
As a part of the ageing process, CD38 and Senescent cell activity both increase, lowering NAD+ levels. Image credit: Buck Institute
The senescent cells secrete a series of pro-inflammatory cytokines, the so-called SASP, which means ‘senescence associated secretory phenotype’.
What we showed is that the SASP is one of the mechanisms by which CD38 increases during aging.
Based on this, one could predict that if we were able to eliminate a senescent cell, we would eliminate the SASP and then we would eliminate the induction of the CD38 expression.
One thing to remember is that the SASP is not the only mechanism that was responsible for the induction of CD38. There were other substrates including bacterial products such as LPS (lipopolysaccharide), and other series’ of factors that we will also have to control.
So I believe that fighting the induction of CD38 is going to be harder than inhibiting CD38 expression or providing NMN as an exogenous substrate.
“if we were able to eliminate a senescent cell, we would eliminate the SASP and then we would eliminate the induction of the CD38”
NAD Boosting Supplements: More Options on the Horizon?
LB: With a forward looking approach on NAD boosting, NAD precursors and their role in alleviating some of the pressures of aging, do you believe we are likely to see a wider variety of NAD boosting supplements emerge over the next 5-10 years?
If so, what form might these (strategies) take? The recent discoveries around the reduced form of NMN (NMNH) is one such example.
EV: This is a very good point, and one I think is exciting. Clearly, what the data shows is the interconnectedness between multiple processes is something that we had actually not fully appreciated.
One is NAD degradation, that’s the role of CD38. The role of senescence. The role of what we call the PAMPs (pathogen associated molecular phenotypes) such as LPS and others.
So, if you think about fighting aging and its manifestations, I would predict that in the future, we will likely have a combination of these approaches to really maintain NAD levels, to eliminate senescent cells, and to restore NAD levels, using a variety of precursors.
“I can predict, based on what has been published and what we know, that there will be other [NAD boosting] molecules.”
Right now, the field is focusing on NR (nicotinamide riboside) and NMN (mononucleotide nicotinamide). Both of those have shown remarkable activities, which is why there is so much excitement in this field.
But I can predict, based on what has been published and what we know, that there will be other molecules.
One thing that is really important to realize is that to be truly demonstrated as efficacious, I think it will be important for these molecules – whatever they are, whether they are CD38 inhibitors or NAD precursors – we need to conduct clinical trials to make sure that whatever we’re giving to patients is not only given at the right dose, but is safe and actually has the intended safety profile and the intended benefit.
I think this is the way that truly evidence-based medicine has been progressing over the last 100 years and I hope that our field of aging research will abide by this principle and demonstrate the efficacy of what we’re providing to patients.
Wearing Two Hats: Bridging the Gap Between Ageing Research and Deploying Interventions
LB: Dr. Verdin, could you comment on the importance of translational roles, such as your role as Chair of the Seneque Scientific Advisory Board, in bridging the gap between ageing research and making relevant treatments available to the general public?
While keeping a foot in both the ‘research’ and ‘commercial’ camps can be difficult to navigate, surely they are likely to become more common as this field matures?
EV: I am very excited by the ongoing opportunity and ability to not only conduct basic research and make discoveries – that’s been my whole life’s work.
But as I’m getting older I have been increasingly interested in taking things one step further and really pushing the envelope to make these discoveries closer to translation in humans.
This is certainly the approach we’re taking at the Buck Institute. We’re starting companies, we’re collaborating with established pharmaceutical companies, we’re collaborating with biotech companies such as Seneque.
I very much view my role not only as Director of a basic research institute, but as an advocate for pushing these discoveries into the clinics. And I really think the science is there in terms of the promise.
“I hope that in 20 years from now, we’ll look back at the Buck and say that this was an institute that really took the bull by the horns and really tried to change the way we age”
The deep questioning and the hard work start now. Which is to say really bring this into humans. We know from data in the pharma industry that it is much harder to translate into humans, especially given the diversity of the human population both in terms of genetics and lifestyle and so on.
One of the reasons we work closely with Seneque is the value they place on proper clinical research. They have a significant program of clinical trials in play which will drive the understanding of the effects of NMN in humans for all of us.
Seneque’s mission is to increase healthspan by 20% in the next decade.
In the future we will hopefully see that in some way the Buck successfully redefined what the basic research institute is doing.
In this case we are aggressively building a translational infrastructure – by collaborating with pharma and biotech and also by starting our own company.
I hope that in 20 years from now, we’ll look back at the Buck and say that this was an institute that really took the bull by the horns and really tried to change the way we age, not only in animal models but in humans. I think this is a little different from what most places do, but I find it very exciting.
“As I’m getting older I have been increasingly interested in taking things one step further and really pushing the envelope to make these discoveries closer to translation in humans.”
Dr. Verdin’s Personal Approach to Longevity. Does Dr. Eric Verdin take NMN? What supplements does Dr Verdin Take?
LB: Dr Verdin, changing gears, as we close off the interview - could you share with our audience one or two of your personal longevity strategies?
EV: I have to be careful here, because these are not ‘recommendations’, this is strictly what I do as a person. I believe in lifestyle effect being very critical in determining longevity, so I really focus on five different aspects.
Nutrition & Fasting
One is nutrition, with a focus on intermittent fasting. Every three months, I do a week of fasting. I do time-restricted feeding, which means I eat for about eight hours of the day and do not eat for the remaining 16. So that’s pillar number one – nutrition.
Exercise
Pillar number two is exercise. I try to fit in between one and two hours of exercise every day. I think it is the best and safest anti-aging medicine that we have today, and it will remain so for a little while longer, until we discover better medicine.
“I used to be an every-day-one-glass-of-wine drinker. I have seen how much this alters the quality of my sleep and I would now define myself as an occasional rare drinker.”
Sleep
The third pillar is sleep. I think we live in a society that is chronically sleep-deprived. I try to sleep a good amount every day and try to make sure it’s good quality by mitigating all the factors that I’ve discovered actually interfere with my sleep.
I use an Oura ring and the Whoop, which are two wearable devices that allow you to closely monitor your sleep and which have allowed me to determine what the factors are that affect the quality of my sleep.
One of the ones that actually surprised me was the effect of alcohol. I used to be an every-day-one-glass-of-wine drinker. I have seen how much this alters the quality of my sleep and I would now define myself as an occasional rare drinker.
Stress Management
The last thing is stress. I really believe that stress is a significant contributor to aging, so I try to mitigate my stress by doing yoga, by meditating when I have the time and really try to mitigate the factors that stress me. For me, exercise is probably the best anti-stressor.
Supplement Routine
In terms of supplements, I believe in measuring whatever can be measured in your blood.
There are number of companies that provide this type of services and in correcting what seems to be off-balance. So I take a number of supplements, simple ones like vitamin D and vitamin B12.
I also take NMN every day. Having taken it myself at significant doses, I really see the effects, so I’m encouraged to continue.
I take metformin for two reasons. First, it’s been shown to have many properties as an anti-aging medicine. But also my fasting blood sugar was borderline and I thought that, given my age, there were little risks in taking metformin.
So there you are – the pillars of my health or longevity program at this point.
LB: Dr. Verdin, thank you so much for taking the time to answer our questions. It is a true privilege to hear from one of the aging’s sectors most notable and well respected leaders.
Looking for more NMN based content? Look no further
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Mole check technology for skin cancer screening: An Interview with MoleMap’s Chief Customer officer
In our previous post, our Founder Nick shared his personal experience with a detailed skin cancer check with the Australian based company Mole Map.
Mole Map is an innovative organisation who have more than 25 years of experience in skin cancer screening, and have pioneered new technology for imaging skin lesions (aka your moles) as well as a ‘surveillance’ system for tracking your skin continually over time.
Today, we’re following up on that content with an in-depth and exclusive interview with MoleMap’s Chief Customer Officer Vlad Mehakovic.
In this interview, we discuss the basics on how the service works, as well as Vlad’s own motivations for joining the company nearly two years ago.
With the basics covered, we dive into the details on how their ‘surveillance’ approach is enabling customers to manage their unique skin cancer longevity risk, and why the business model has been such a success.
Also, we ask Vlad a series of questions on where skin cancer surveillance is headed in the future.
This has some exciting answers, including emerging opportunities for the application of artificial intelligence to the skin cancer detection challenge, as well as a future where more of us are empowered to self-monitor our own skin using apps (some of which are freely available from Mole Map already).
There’s even a cool AI start-up company in the mix! There is plenty to learn about in this post, so without further delay, let’s chat with Vlad from MoleMap.
This interview was conducted on 20 May 2021, over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Our guest - Vlad Mehakovic, Chief Customer Office at MoleMap
Longevity Blog (LB):Vlad, thanks so much for joining us today. To kick things off - could you give us a brief history of MoleMap and its mission?
Vlad Mehakovic (VM): Thanks for having me!
MoleMap was started about 25 years ago by a group of medical entrepreneurs. Their key innovation was creating a system for better skin cancer diagnosis. Not only a set of hardware and software technologies, but also a system that took the dermatologist away from having to do the screening process themselves.
We see ourselves as pioneers within telehealth. What we've been doing is taking specialised photography and sending them to a remote dermatologist for review - and we’ve been doing that for 25 years.
How does skin cancer screening work?
LB: Those early medical entrepreneurs, they saw a specific ‘gap’ in the diagnostic capability. Could you comment on that gap? What was it?
VM: It comes down to standardisation. We've got a standardised way to map at your entire body, at a macro level. We then go micro and do diagnosis when there are lesions (medical term for all types of moles) of risk. These risky lesions are identified by a trained registered nurse (melanographer), they will take macro images of your skin followed by a micro, very close up, image of your skin. This is completed with a specialized camera (Molecam). [See the process yourself in Nick’s post about his MoleMap visit]
This camera can see under the first few layers of your skin. Those images are then passed on to a dermatologist who reviews them remotely. We've built one of the best dermatologist teams in Australia and New Zealand, some real leaders in dermatology.
A ‘melanographer’ use a ‘Molecam’ to image a mole on Nick’s foot!
This team-up between the melanographers and dermatologists with high quality images, allows people to track their body over time. This is the ‘surveillance system’ in action. It's not a one time solution, it's something that you repeat over time. This is important because skin lesions can change very quickly.
LB: MoleMap has clearly built a talented team, and have creatively structured the business so you can pull in the best dermatologists to review the images, leaving the technical side of assessing the skin and taking images to the melanographer. It’s a great model.
Speaking of talented people coming into the company, you're the Chief Customer Officer and have been in that role for going on two years now. Talk us through what drew you to MoleMap?
VM: I came onboard as a consultant initially and I saw lots of opportunities for growth. After a few months a new CEO (Tanya Houghton) came on board. Everything was working well, and I really liked the company. I was really honored when she asked me to keep on working with business.
LB: We like how you're talking about a team who is continuing to pioneer technology for skin cancer surveillance. It is quite a remarkable success story of applying a technology to cancer detection.
Does Skin Cancer Screening Save Lives?
LB: Can you tell us in the instance of skin cancer, why does early screening, save lives?
MoleMap provide extensive literature and supporting information about the many types of skin lesions, and the ones you need to watch out for
VM: It’s a pretty simple equation - the less cancerous tissue there is to remove, the less likely that cancer is getting into the bloodstream. The earlier you remove them, the higher the rate of survival. It's really that simple.
Again, it's not necessarily just the technology, it's the system that we offer, that really offers the step-change. There are a lot of different medical professionals, even with good technology, good dermascopes, but they don't necessarily get their education updated after attending med school. It is the application and the surveillance system that allows us to detect skin cancer systematically and comprehensively.
LB: In our Founder Nick’s personal experience with MoleMap, he reviewed the very technical way you map the entire body. It first calls out areas of interest, but then, of course, requires the user to come back.
It seems that this surveillance system has been remarkably successful. MoleMap have seen over 300,000 patients, mapped over 5 million moles. Can you take that a step further? What is the likelihood that this surveillance approach will save somebody's life?
VM: On average, we’ll see a bit more than 50,000 people a year, and that grows every year. About 30% will have some sort of recommended action. Most often, that is to continue monitoring a lesion closely.
We've started providing an increasing number of free tools for our patients & non-patients alike, to help support them. One of these is a web application that allows you to track your own lesions over time. This web app can also integrate that with the professionally taken photographs from our clinic.
So of those 30% where we advise continual monitoring, around 3% of people need urgent attention. We call them straight away and advise to see a dermatologist immediately.
If Skin Cancer Screening Reveals an Issue, What Next?
LB: In the case of a finding that is immediately actionable, talk us through what happens next for a patient.
VM: If there is a lesion requiring urgent attention, we'll call that patient to find out if they've got an existing dermatologist or GP whom we can send them a copy of our detailed report. If the patient gives permission, we send off the report and then the practitioner will understand what needs to be done and can act swiftly.
LB: In the case where there's an immediate finding we could argue the MoleMap visit has been a life saving intervention.
Should I Get a Skin Cancer Check?
LB: Coming back to those 50,000 or so people that come every year, nearly 40% of Australians have never had a skin cancer check, and many more of them fail to do it regularly. Why do you think it is such a difficult thing for people to manage? Why don’t more people complete regular skin cancer screenings?
VM: Compliance is a difficult thing, full stop. The number one barrier we talk about is apathy, as in, it won't happen to me. The main driver we see that finally gets people to act is when someone close to them - a loved one, a close friend - is diagnosed with skin cancer or dies from it. In the case of males, it's usually a spouse that drives them in to get screened. To be honest, guys don't tend to come in of their own accord.
LB: This is where we wanted to pivot to next - these objections: apathy, time, budget, nerves - what are some elements of the MoleMap service that help people get past those barriers and into a regular screening program?
VM: Our core service is going to cost what it's going to cost. So really, when people talk about cost, they're talking about value. What we're trying to do is support people in and around the visit, even before the visit.
Software management tools are a great example. First, risk assessment - we've got an online risk assessment. We also provide a free service where you can talk to one of our melanographers for 15 minutes to assess your risk and find the right service fit for your needs. We have a free online body map tracker, which allows you to actually track your own moles for a period of time.
“The number one barrier we talk about is apathy, as in, it won’t happen to me.”
Skin Cancer Screening with your GP?
LB: We understand there is currently an effort to get your technology directly into the GP room. In this model, GPs are provided the same system you offer and you train their nurse staff to complete the assessment. Tell us about the maturity of this strategy - Is it a pilot project? Or is this something you're in the process of going more widely?
VM: The pilot is well and truly done, and we've validated that it makes sense. It's got a lot of interest. We've rolled it out successfully in a number of practices across Australia, and we're beginning to roll that out in in New Zealand as well. It's going extremely well
LB: Is this something Australian’s should be asking their GP about - saying “Hey, have you heard about the MoleMap technology? I'm interested”.
VM: Look, that would be lovely. A significant number of GP visits are already skin related, and GPs are increasingly, in the last decade becoming increasingly educated around skin diagnosis. It's an already growing aspect of general practice. We're coming in with a holistic solution that hopefully, increases the patient outcome while decreasing the workload on the practice.
Artificial Intelligence for Skin Cancer Screening
LB: Continuing down the technology angle, looking into the future, MoleMap have created a very large database of skin lesions. Upon each visit, there is an opportunity for patients to opt in to allow their moles to be part of R&D.
Let's talk about MoleMaps R&D a bit, specifically where skin cancer detection technology is going in the future. As a starting point - explain what happens when one of your patients opts-in to allows their anonymous mole/lesion images to be sent off to improve the detection technology? What's happening there? What is their contribution, so to speak?
VM: Our vision is a world where all skin cancers get diagnosed and treated. That means we need to have a variety of options and solutions. The more lesion images that we can capture and categorise, the better that we can achieve that outcome. So that means we've got to look a lot further than just our own clinics.
MoleMap operates the biggest database of high resolution skin lesion images in the world. Perfect for training Artificial Intelligence algorithms. Picture: one of Nick’s moles that he needs to track!
We're starting to do that by offering that service to GPs and we are in the talks with a couple of big pharmacies. We have a workplace program where we come into your office.
About three years ago, we kicked off a process with IBM, because we have the biggest database in the world of high quality dermatologist diagnosed and categorized skin lesions approved to be used for research and development.
“Our vision is a world where all skin cancers get diagnosed and treated”
LB: That is a highly valuable and unique asset. So, what are your plans for this database?
VM: For the last three years, we've been using that imagery to train an artificial intelligence algorithm. Specifically, a convolutional neural network. And we’re continuing to optimise its ability to categorise skin cancers correctly.
We’ve also been working with Monash University, which has progressed to the stage where we've been comfortable enough to really want to invest in the commercialization of that technology. About six months ago, we formed a start-up company. It’s a stellar team of both technical business people, but also scientists within AI that have applied AI commercially in medical imaging in the past.
The team is now in the process of regulatory approval, which means, number one, being able to use that AI as a medical device. Secondly, the team needs to figure out how it makes sense to take it to market.
LB: Is this company currently in stealth mode, or can we know its name?
VM: Oh, it's called. It's called kāhu, named after a large hawk known for its sharp vision. The only thing that’s really stealth is what exactly the product is going to be. We've got some tight time pressures on that team and are expecting to get it to market quickly.
How Might AI Change The Skin Cancer Screening Process?
LB: When it does come to market, what is the vision for how that might change diagnosis or the surveillance process for catching potentially cancerous lesions?
AI will assist dermatologists by reducing the time they need to spend assessing each skin lesion.
VM: Well, again, if we go back to our global vision of the business, we're trying to get more images diagnosed. So this potentially helps that happen. It's unlikely that it's going to be the case where there is no human intervention. If you look at a lot of the best applications of AI, it's assisting an existing professional in the decision making rather than taking over the decision making process.
The AI technology would most likely be running alongside an already trained healthcare professional. It’s main potential is to deliver a higher level outcome to a wider audience - in other words, deliver the same level of diagnosis and categorization and patient outcomes, without having to have as much specialist contribution for every single lesion.
The Future of Skin Cancer Screening is Based on enabling patients to self-manage risk
LB: That's a great answer. Just as an aside to that, it was actually announced just today that Google had launched an AI health tool for skin conditions, including skin cancer. So that is another signal that artificial intelligence and good data sets in skin health is part of the future.
Pulling from your insights and some of the things you just talked about, what is your vision for how skin cancer diagnosis and treatment is going to change in the next 5 to 10 years?
VM: I think the key thing is, we've got to think about how to enable the patient to better manage risk themselves. There's a couple of levels of triage that happen. A patient goes to see a doctor, when they've got an issue, usually it is their family GP. They go and see that person for advice.
MOBILE APPS FOR SKIN CANCER?
Longevity Blog will soon be reviewing a selection of DIY options for skin cancer screening, be sure to subscribe below to get notified when that new content arrives!
Now, the nature of that is changing somewhat. There are now a number of mobile applications that are claiming various things that you can do by taking a photo of your skin with your phone and performing self-tracking. But the truth is the quality of those images and the ability of those people to really do the same job as a trained professional - there's quite a gap.
What we need to be able to do is get the best system and solution in as many doorways where patients are already visiting, as possible. The intent for us is really Australia and New Zealand as a testbed, before we begin to export globally. But we want to prove the case, really solidly here first, before we start to look at those options.
Bulk Billed Skin Cancer Checks
LB: Your answer actually flows on really nicely to an Australian specific question - when can we expect ‘bulk billed’ skin cancer checks to become available? It’s a legitimate question, given the prevalence of the disease in Aussies.
Is there a future for bulk-billed skin cancer checks in Australia? Not anytime soon, unfortunately
VM: We haven't heard any plans, even of it being reviewed. We don't go out and lobby or do anything like that. For us it's a step by step approach. We know that Medicare coverage for these checks would be hugely powerful. It would be good for Australians, it would be good for skin cancer diagnosis.
The first step that we can take, and we’re making some headway with, is working with major private insurance providers. More than one of the major private insurance companies in Australia are interested, and we're talking things through. We’re hoping to launch some partnerships very soon. That would be a really good first first step.
LB: At least there's some hope in the future with private health cover!
VLAD’s Personal Approach to Longevity
LB: We're gonna wrap this interview up now, Vlad, but before you go we always like to ask interviewees a little bit about what they do for their own longevity and health. To start, do you use the MoleMap technology yourself?
VM: Yeah, of course! I believe in proactive health management. I have an annual week of bloods, gut, dentistry, skin health that I personally go through. It's almost that via negativa process of ruling out the worst conditions. I totally believe in proactive health management to increase longevity and quality of life.
LB: Great to hear that! What have you learned from that week of focus that could be valuable to our readers in terms of putting together their own longevity strategy?
Establishing a good working with your personal doctor is a key longevity tip from Vlad. (GP = general practitioner, the same as Primary Care Physician in the US).
VM: I've got a great holistic GP, and I've started educating myself around the importance of gut health, more so than anything else. I know that skin cancer is bad, of course, and I need to be monitoring it. I know that heart attacks and strokes are bad, and I should be monitoring them. Putting it all together makes sense.
LB: So a good relationship with a high quality doctor has been one of the most important parts of that journey for you, as well as taking initiative to educate yourself on longevity risks.
VM: Yeah, totally!
LB: Thank you so much for contributing today, Vlad. We really appreciate it!
VM: Thanks mate!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Urolithin A, Endurance, Muscle Strength and the Longevity Future - An Interview with Amazentis CMO Federico Luna (Pt 2)
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Urolithin A Supplement Benefits: Endurance and Muscle Strength
Studying the effectiveness and safety of Urolithin A in human subjects has led to some exciting results in muscular endurance, strength and power.
To date, the research efforts into these benefits have been led by Swiss bioscience company Amazentis, who now sell a Urolithin A supplement under their “Timeline” nutrition brand.
This product “Mitopure” is a high purity form of Urolithin A, which as we discussed in the previous post, has been shown to have excellent bioavailability a in clinical trial setting.
Amazentis has run three clinical trials (in humans) on Mitopure as of this interview (Q1 2021).
Timeline’s Mitopure
Perhaps the most notable findings in their clinical trials so far have been the impressive benefits in skeletal muscle.
These results are notable because they are potentially important one with respect to your longevity.
Aging is known to be associated with loss of muscle mass and power, which is driven by a multitude of factors - including confusion in important signalling pathways within the skeletal muscle due to dysfunctional mitochondria.
Urolithin A acts upon the dysfunctional mitochondria in skeletal muscle by triggering mitophagy - which is the process by which these dysfunctional mitochondria die off, and are replaced by new, healthy mitochondria.
For more on this, we’ll let Federico add to the details. Without further delay, we continue our interview with Amazentis CMO Federico Luna.
[If you’ve not read part one of this interview, you can find it here]
This interview was conducted on 30 March 2021, over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
This is part two of a two part interview. Part one of this interview is available here.
Urolithin A and Muscular Endurance
Longevity Blog (LB):
On the topic of mitophagy and muscle tissue, let’s come back around to this 40%+ improvement in running endurance in mice, as compared to untreated peers of the same age.
It naturally starts a conversation around whether Mitopure could improve athletic performance. Clearly. you haven't studied that yet, but surely you've been asked about it?
Federico Luna:
We're getting a lot of interest from the elite athlete population, as you can imagine. The fact that this is a natural molecule, the fact that it's safe, the fact that there's a growing body of scientific and clinical evidence - that's very exciting. Sports is an area that we're very interested in for sure.
Could Urolithin A be a sport performance supplement? Early results are promising - Longevity Blog will be sure to keep you up to date. Be sure to subscribe for updates!
Today we don't have any clinical studies in this specific population, but we do have some very interesting pre-clinical data in younger mice and also anecdotal feedback from athletes who have been taking Mitopure.
That's purely anecdotal at this stage. But we're very excited about the sports nutrition opportunity and athlete population, for sure.
LB: That really piqued our interest. 40%+ a quite a large improvement in endurance running from a supplement alone.
Thank you for commenting on that. We understand it's anecdotal at this stage, but it could make for some excellent self experimentation in athletes who are curious about the product.
On the topic of performance, let’s discuss the second clinical trial in more detaily. This trial looked at some very specific exercise tolerance metrics - cycling ergometer, handgrip strength, gait speed, lower body muscle strength - to name a few.
Urolithin A Benefits in Leg Muscle
What were the outcomes here? On the website that you refer specifically to hamstring strength as one area of improvement. Patrick Aebischer also mentioned there were some improvements in walking speed on the LLAMA podcast. Could you comment anymore on the outcomes for that clinical trial? How comprehensive were the improvements?
FL: I can only give you a ‘top line overview’. We’re seeing remarkable results on leg muscle strength, the hamstring, as you mentioned. We're seeing significant improvements, both vs baseline and also versus placebo. So, yeah, more to come on that study once it's published.
Leg muscle strength and power are crucial for maintaining independence in aged cohorts. Urolithin A benefits to leg strength are notable to longevity enthusiasts for this very reason.
LB: We'll plan to follow up with your team once that publication comes out. In a follow-up blog entry, so we can explore the details. Let’s talk about that third clinical trial you discussed. What is it exploring?
FL: You know, one of the big questions we often get from people as they start looking into reading about Urolithin A is - where do I get Urolithin A? How many pomegranates do I need to eat?
Up until the launch of Mitopure, there was no consumer product that offered people a pure form of the active.
Urolithin A Pomegranate Power
Sure, you could buy products containing pre-cursors like ellagic acid, pomegranate extract, or even pomegranate juice but you’ll never know how much Urolithin A you’re actually going to get.
What's remarkable about Urolithin A, is that it is an unusual molecule, it’s a metabolite, which means its not in the foods we eat but is produced by our gut after eating certain foods.
When you eat a pomegranate, it has a precursor compound, a family of compounds known as ellagitannins. After you eat the pomegranate, if you've got the right gut microflora , that bacteria then helps metabolize and create the bioactive Urolithin A.
The challenge, unfortunately, is that a lot of people don't have the right gut bacteria. And even if you do have the right bacteria, it's guesswork to figure out how much Urolithin A and whether you’re getting the right dose to reap the health benefits.
“if you’ve got the right gut microflora , that bacteria then helps metabolize and create the bioactive Urolithin A.
The challenge, unfortunately, is that a lot of people don’t have the right gut bacteria. ”
That's where Mitopure is really a breakthrough. There's a decade of work that's behind this - we've found a way to create and bypass the complexity of diet and the microbiome, by providing you a precise dose of the active.
LB: A decade of work but still easier than opening a pomegranate [joking]
FL: [Laughs]. Yeah. We've got a few tips we can share on how to open pomegranates, we've done a fair amount of pomegranate opening over the years.
Mitopure vs Pomegranate Juice for Urolithin A
Pomegranate juice can provide the building blocks of Urolithin A, but the correct gut bacteria are necessary to produce Urolithin A.
LB: The first clinical trial and publication had some excellent graphics exploring various Mitopure dosing strategies, and the resultant blood serum levels.
Have you explored Mitopure versus pomegranate juice in individuals with the correct gut bacteria?
FL: In our next [third] clinical study that we're going to be publishing, it really dives deep into the microbiome and that side-by-side comparison.
It compares the pure form of Urolithin A that Mitopure delivers into the bloodstream versus natural dietary sources, in this case a glass of pomegranate juice.
We took 100% pomegranate juice and did a crossover study with 100 people in Chicago. We compared over a 24 hour period the area under the curve to see total exposure to Urolithin A from natural dietary sources versus Mitopure. The comparison is remarkable.
There's really interesting data coming out in terms of how many people at baseline have Urolithin A in their system, as you can imagine, that's very low. The second data point is - how many people can actually naturally produce Urolithin A from pomegranate juice? That's also low.
The last question is, okay, even of those who can produce Urolithin A, what is the difference? How much do you get from Mitopure, versus how much do you get from a glass of pomegranate juice. We see a six fold higher levels of Urolithin A with Mitopure over a 24 hour period versus pomegranate juice.
LB: So this third clinical trial - it sounds like you're in the data analysis stage, it is completed and you're preparing results?
FL: Correct. We're preparing to publish them.
LB: Do you have an indication on when the preprints for those publications might be showing up? Is that something we could expect in 2021?
FL: Hopefully. The target is to get these published in 2021.
Is Urolithin A from Mitopure Too Expensive?
LB: Great, we’ll be sure to follow up on that. Let’s talk about the Mitopure product. One of the most common objections we’ve read, in our background research for this interview is cost.
People often balk at the price. That is understandable, as it's a relatively expensive supplement at $100 a month. Help us understand that price point.
There's 10 years of work that have gone into this. Amazentis has pioneered this work, but let’s go a bit further into why that number is something that's defensible. Why should a reader invest their budget in Mitopure?
FL: Coming back to the comparison I gave you around pomegranate juice - you know, one glass of pomegranate juice, [Mitopure] is not priced anywhere near to 6x the price of a pomegranate juice. In fact, we're very reasonably priced, if you make that comparison.
Comparing Mitopure vs Pomegranate Juice Cost
We did the comparison, based on Australian prices. $4 for a pomegranate or $6 for 1L of 100% pomegranate juice (from concentrate).
One pomegranate will yield about 150ml of juice. That's 6.6 pomegranates for a 1L at a price of $26.
$26 for 1L of juice is a significant premium ($20) on buying a ‘from concentrate’ source, but likely to be more potent, and is what the ‘6x more effective’ figure is based on, so we need to use ‘fresh’ for a like-for-like comparison.
Our base unit is the 500mg dose of of Urolithin A (the standard Mitopure dosage) versus drinking 8 ounces of pomegranate juice (225ml).
225ml of fresh pomegranate juice would cost $5.85AUD. Multiply that by 6 for a whopping $35 worth of fresh pomegranate juice, not to mention the 1.3L you’d have to drink to get the same Urolithin A benefits (with the right gut flora, of course).
Even with the discount on the ‘'from concentrate’ option at 1.3L, you’d still be paying $7.80AUD.
Mitopure 500mg sachet works out to be $4.30AUD without the subscription discounts.
The takeaway: Federico is right on the maths. if you’re after Urolithin A benefits, Mitopure is a good deal and you’ll have fewer trips to the restroom each day ;)
Is Mitopure too expensive? Not according to the math
FL (cont.): The $100, for some people, we can understand that that's a sticker shock. On the other hand, if you break it down per dose, you're looking at a price of $3.33[USD] per dose. We do actually offer an [annual] plan, which is selling extremely well, where people get a discount - a per dose price of $2.87[USD].
Make the math even better - use the code ‘longevityblog’ to save 5%!
When compared to your alternative, which is, I would say at best a blind gamble with pomegranate juice - here you have a product that can deliver six times more at a relatively small premium.
Obviously, we're hoping over time, as more and more people start benefiting from Mitopure, that as our volumes increase - we'll be able to reduce cost and offer people an even better price.
LB: We will do that calculation to pomegranate juice, for the benefit of the readers just check that out.
One of the things that is often valuable in this case, are customer testimonials. You earlier mentioned you're getting some positive feedback. How does someone know that their investment in Mitopure is working for them? What feedback do you hear?
Urolithin A Benefits: What customers are saying about Mitopure
FL: I can't share details just yet what those testimonials are. What I can tell you is - we're getting great feedback. Biology is very personal, there is no average patient in a clinical study, as they say.
As you’d expect a few people are saying it's either too early to tell or some people don't necessarily feel a measurable difference. The majority however are giving us remarkable feedback.
We’re hearing from a variety of age groups - people as young as 30, all the way to people in their 80s talking about benefits in terms of energy and strength. Those are sort of the two primary areas where we're getting positive feedback.
We're working on taking all these great testimonials and making them available - because we do get that question a lot.
LB: Thanks for sharing that. We understand that individual biology is complicated. Everybody is their own self experiment. That's actually one of the things that Longevity Blog focuses on - helping people learn to take one thing at a time and measure meaningfully whether or not it's benefiting them.
Urolithin A and Mitopure: What’s Next?
Amazentis CMO Federico Luna - with a pomegranate, of course!
So energy and strength - that feedback matches with the research. There's also been other complimentary research on Urolithin A. Particularly around helping the gut barrier heal in cases of ulcerative colitis or irritable bowel syndrome.
Others have focused on neurodegenerative disease and also found a role for Urolithin A in triggering of autophagy. That work by Julie Anderson's group at the Buck Institute.
How do you feel the work of Amazentis has helped to ‘move the needle’, so to speak, in terms of the interest in Urolithin A more broadly?
Do you expect that the research in this area will be maturing quite quickly over the next few years?
Urolithin A science is moving quickly
FL: We've seen tremendous excitement from the scientific community. Again, if you look at PubMed as a source, typing ‘Urolithin A’ into PubMed - you'll see there's been an explosion of preclinical research over the past 10 years.
You mentioned the Buck. Its a remarkable research institution and Julie Anderson's lab is doing groundbreaking work on Urolithin A and Alzheimer's. There are a number of other leading researchers around the world pioneering new potential applications for Urolithin A. Interest is really growing.
The fact that Amazentis’ pioneered the first translation of the science into humans - I think that gives researchers the confidence. It’s been shown to do something in worms, it's something that's been shown to do something in mice.
Now there's very promising data in humans. We think that will catapult Urolithin A research over the next few years. We like to think of Urolithin A as sort of the ‘next omega 3’ and while there is a strong body of evidence already today, there’s much more to come.
LB: That's a fascinating answer. We're coming up on the end of our time here. So let's try to draw it to a close, by thinking about where this particular supplement (Mitopure) and the Timeline Nutrition brand are going to fit in the personal longevity strategies for people moving forward.
This particularly supplement seems to be filling a niche around loss of muscle mass and power as we age, as well a loss of energy as we age. Coming back to your company mission, your ‘science first’ approach, at Amazentis - where do you see Amazentis contributing to improving our healthspans over time?
The Amazentis & Timeline Mission
“It’s a really exciting time for longevity. It’s a really exciting time for muscle health. And we’re just at the beginning”
FL: Our mission is to optimize cellular health and help people live healthier lives for longer. As we talk to people, and take them through the science, particularly around muscle, people are surprised at how early our muscle health actually peaks.
There isn't an exact number, it varies from person to person, but we've seen studies that show muscle starts to peak in our 30s or 40s.
One of the big challenges in health is getting people to invest in prevention, because while we all like the sound of prevention, when it comes down to it - are you willing to invest in your health?
What's really exciting is we're seeing more and more people say - “Yes, I want to invest in my health, and I want to invest now”. So that I don't have to try to cure later on in life. That growing buy into prevention coupled with the data we have that shows that Mitopure can have in impact on your muscle health in 2-4 months is a great match.
It's a really exciting time for longevity. It's a really exciting time for muscle health. And we're just at the beginning. And, the fact that we've got the first and only clinically tested, pure form of Urolithin A, and we're offering that direct to consumers, through the Timeline brand and also through a great partnership with Nestle Health Science - arguably one of the leading global players in science driven nutrition is the perfect combo. We think this is just the beginning of a really exciting portfolio of products and innovations and things to come on Urolithin A.
LB: Fantastic. We look forward to staying in touch with you on that future vision, Federico. Particularly we look forward to those upcoming clinical trial results, as well as how you'll be expanding your partnerships and improving access to the forthcoming healthspan boosting technologies in the pipeline. It's exciting stuff. Thanks for speaking with us today.
FL: A pleasure! Thank you.
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Urolithin A Supplement - Benefits, Side Effects, Healthy Mitochondria
You can now score 5% off Mitopure with our exclusive discount code!
Use the code ‘longevityblog’ save 5% after adding an item to your cart & creating an account.
Urolithin A Supplement Benefits
In this post we’ll cover:
The top benefits of Urolithin A supplementation
What is Urolithin A and is it safe?
Urolithin A supplement Mitopure
Interview with topic expert Federico Luna of Amazentis, including
Urolithin A clinical trials
Mitophagy and improved mitochondrial function
Urolithin A in the Body
Urolithin A is certainly turning some heads in the longevity & wellness biohacking community, owing to an unusually wide array of purported benefits. Chief amongst them - improving mitochondrial health.
Urolithin A (UA) is a new longevity supplement with excellent results in placebo controlled human clinical trials. In this post, we’ll learn about what it is, its benefits, side effects and where to get it + save 5% off the best available option. we’ll also hear from an expert on the latest science.
Urolithin A Benefits
Urolithin A supplement benefits video with our Founder Nick.
UA and Gut Health
UA has shown remarkable benefits in the digestive track, with an apparent ability to heal the all-important and notably fragile, gut-barrier.
Currently being explored in non-human studies, Urolithin A appears to offer notable levels of improvement for irritable bowel syndrome and Crohn’s disease. These benefits also appear to extend to colon cancer.
Improvement to the gut microbiome and gut bacteria requires a strong gut-barrier and is linked to many positive health benefits. Therefore, it seems UA is clearly quite good for your gut!
Read the Nature Communications article on Urolithin A benefits in the gut here
UA Cleans Up Metabolism
Urolithin A (and B) appear to possess anti-glycative properties, meaning they can help prevent the accumulation of advanced glycation end-products or AGEs which leading to age-related complications such as the loss of flexibility in tissues with age.
Similar mechanisms may also link Urolithin A benefits to neurodegenerative disease, currently being researched in the (Julie) Anderson lab at the Buck Institute.
UA and Muscle Strength
Perhaps the most interesting benefits are observed in mitochondrial health and skeletal muscle, which have recently been discovered in randomized double blind placebo controlled clinical trials through research led by Amazentis (2019 to present).
In our upcoming interview, we’ll focusing specifically on the ability of Urolithin A to improve mitochondrial function and restore healthy mitochondria in the skeletal muscle.
But first, what is Urolithin A exactly?
What is Urolithin A?
Given Urolithin A is demonstrating extraordinary promise in a few key areas of age-related disease, it’s natural to be curious about what it is and where it comes from.
Urolithins are a by-product of the digestion of ellagitannins, which are found in certain foods, including raspberries, walnuts and pomegranate, which also include the polyphenol ellagic acid.
Before you jump toward filling up the shopping trolley with pomegranate juice, note that urolithins are only produced by certain types of gut flora, who participate in the digestion of ellagitannins.
Only 20-30% of people are thought to have the right gut microbiome to complete this conversion, and the ability to produce urolithins in the bloodstream. They naturally have UA levels several times higher than those who do not have these gut flora (who may have no UA in their bloodstream at all!).
We’ve completed a thorough Urolithin A supplement review, including a self-experiment guide to see if Urolithin A supplementation will work for you! Read it here.
Is Urolithin A safe? Urolithin A Side Effects?
The inability of most people to produce Urolithin A has given rise to the first Urolithin A supplementation options.
Notably, using Urolithin A as a dietary supplement has achieved GRAS status from the US FDA (2018), meaning it is ‘Generally Recognised as Safe’ for human consumption in the proscribed range of 250 mg to 1000mg per dose.
Urolithin A does not have any documented adverse side effects - provided you choose from a high quality provider. As per usual, many imposters exist on eBay and Amazon - buyer beware! (We write more about this issue here)
The Best Urolithin A supplement
‘Mitopure’ is a Urolithin A supplement, and the focus of our interview content in this post.
Studying the effectiveness and safety of Urolithin A in human subjects, is what leads us into our interview subject - Swiss bioscience company Amazentis and their recently launched (2019) “Timeline” nutrition brand.
Their mainstay product “Mitopure”, is a Urolithin A supplement, brought to market in the culmination of more than ten years of scientific work, including capstone clinical trials in human subjects.
The Timeline brand’s ‘Mitopure’ is a high purity form of Urolithin A with excellent bioavailability (proven in clinical trials which we will discuss shortly), demonstrated to show up in the blood supply after supplementation.
Urolithin A in Humans
Amazentis’ growing number of clinical trials in humans has demonstrated Urolithin A to function as a catalyst for mitophagy, which is the orderly death of dysfunctional mitochondria.
This has been demonstrated to be specifically helpful in skeletal muscle, which accumulates an increased number of dysfunctional mitochondria as we age.
These benefits look to be a welcome ally in the struggle against loss of muscle mass and power with age, and there is early evidence Urolithin A supplementation is particularly effective for this purpose in leg muscle.
To dive deeper into these fascinating and promising results we completed a detailed interview with Amazentis Chief Marketing Officer Federico Luna, to get into the nitty gritty details and enable our readers to make an informed decision on whether or not to self-experiment with Urolithin A.
This interview was conducted on 30 March 2021, over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Longevity Blog (LB):
Federico, thank you for joining us today. To start out, let’s discuss the central values of your venture. Timeline refers to itself as a “science-first nutrition brand”, explain what this means, and how it might differentiate you from other companies which sell dietary supplements?
Federico Luna (FL):
Our interview guest, Federico Luna, Chief Marketing Officer at Amazentis + our subject matter pomegranate!
Great question. There's a lot of brands out there that call themselves science driven. We thought hard about how we are different to that.
It's difficult in a world where perception is everything, and anyone can put a couple of words on a website, and consumers interpret that as sort of very high science.
‘Science first’ means a couple of very concrete things.
Unlike many nutrition companies, Amazentis was founded by leading scientists, doctors and entrepreneurs in the life sciences who wanted to create a new class of nutrition supported by the rigor of research you typically only find in biotechs that are developing drugs.
The company invested over a decade into research before commercializing its first product, Mitopure (the first clinically tested pure form of Urolithin A). Our primary focus for all these years has been to pioneer the pre-clinical and clinical trials with this novel molecule, Urolithin A.
We started with preclinical trials, using tiny little worms called C. elegans, and showed that these worms were living close to 40-45% longer after taking your Urolithin-A compared to placebo. We then took it into mice, and started learning more about the running endurance and muscle health potential benefits.
And now we’re translating this science into humans. In the last five years, we've run multiple human clinical trials. This approach is what we mean when we say ‘science first’. You do the rigorous science first, and only then go to market.
Amazentis - Pioneers and Experts on Urolithin A
LB: It sounds like what we are hearing from you, is that Amazentis has been leading in this research area, since the beginning. We might have to consider Amazentis to really be the authority on Urolithin A? Would you agree with that statement?
FL: Many researchers around the world are doing interesting studies with Urolithin A. And in the last 10 years alone, if you go to pubmed.org, you'll find over 100, preclinical studies, exploring the benefits of Urolithin A.
Not only for muscle, but also for brain and other very important organs. But Amazentis is the first and only company that has taken Urolithin A into the clinic with very rigorous double blind placebo controlled trials.
Urolithin A Clinical Trials
LB: To date there have been two clinical trials in humans, is that correct?
FL: There's actually been three. One with published results in Nature Metabolism.
The purpose of this first trial was a couple of things. First and foremost, was to establish safety. So that was the primary endpoint. But what was fascinating and remarkable is we also started looking at the impact of Urolithin A on mitochondrial function, and more specifically on gene expression.
LB: Let's talk a little bit about that first trial and follow-up publication. One of the most notable things about the study was the proof of the bioavailability of Mitopure. It demonstrated that Urolithin A is getting into the bloodstream and spreading throughout the rest of the body.
Help our readers understand - why is this such an important and significant finding? Can you walk us through what that means in terms of the downstream effects?
Mitopure supplementation at 250mg, 500mg and 1000mg in human subjects, with the concentrations of Urolithin A and its metabolites (UA glucuronide, UA sulphate) in the blood.
FL: One of the key outcomes of this study was a characterization of the pharmacokinetic profile of Urolithin A in humans. We wanted to understand the absorption, bioavailability, distribution and excretion of different doses of UA.
We found that UA was bioavailable in plasma at all doses tested, which is indicative of its potential to have a systemic impact and it also gave us insight into the right dosing to take into subsequent clinical trials.
If you think about mitochondria, these little energy factories inside of most of our cells – in the brain, in our muscle, our eyes, our liver, in a number of key organs - by looking at the bloodstream, we're gaining more insight on how Urolithin A could act on the mitochondria, across all these other potential organs.
“We found that Urolithin A was bioavailable in plasma at all doses (of Mitopure) tested, which is indicative of its potential to have a systemic impact”
The second thing we did is look at the muscle specifically. We wanted to understand if the molecule can actually make it into specific muscle tissues. That's very important for the molecule to have a local effect.
LB: One interesting aspect about that publication was in the concluding remarks, where the effects were described to ‘resemble a regular exercise regimen’. While we don't quite have that elusive ‘exercise in the pill’ solution yet, it does seem that Mitopure may be conveying many of the benefits of exercise.
How can your Urolithin A supplement benefit sedentary folks and folks who are perhaps a bit older and losing muscle strength and power?
Urolithin A restores healthy mitochondrial function
FL: If you think about the mechanism of action here, what we've shown is Urolithin A acts on the mitochondria. Even more specifically, it acts on the mitophagy pathway. In short, mitophagy is a natural cleansing and renewal process whereby damaged and inefficient mitochondria are identified and cleared away.
This makes room for new healthy mitochondria, a process known as [mitochondrial] biogenesis to kick in and help create and rejuvenate the mitochondria.
This mitophagy pathway is really a breakthrough scientific discovery. A lot of that work was led by Professor Johan Auwerx, here at [Laboratory for Integrated and Systems Physiology at École Polytechnique Fédérale].
Love podcasts? Live Long and Master Aging is one of the best in the longevity field. Listen to an interview about Urolithin A with Chairman of Amazentis’ Scientific Advisory Board Patrick Aebischer.
As you look at mitophagy and inducers of mitophagy, exercise is a one, another key one is caloric restriction.
We don't see Mitopure as a substitute or replacement, but as complimentary to physical exercise and caloric restriction.
LB: Patrick Aebischer (Chairman of the Amazentis Scientific Advisory Board) said previously on a podcast in 2020, that Mitopure was the only known compound capable of simulating mitophagy. Do you still know if that's still believed to be the case?
Mitopure: The Best Urolithin A Supplement?
FL: This is a rapidly evolving space and there's a lot of ongoing scientific research. So I can't comment in absolute terms. What we do know is Mitopure is the only mitophagy inducer that has been taken into the clinic and has been shown to improve mitochondrial function and muscle strength in humans.
LB: On the topic of mitophagy and muscle tissue, let’s come back around to this 40%+ improvement in running endurance in mice, as compared to untreated peers of the same age.
It naturally starts a conversation around whether Mitopure could improve athletic performance…
Want to learn more? Read Part 2 of our Interview Here
You can also check-out our Urolithin A supplement review and self-experiment guide here
We’ve negotiated a discount on Timeline Nutrition’s Urolithin A supplement “Mitopure” for our readers.
Use the code ‘longevityblog’ at the Timeline Nutrition website to save 5% on any order
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.