AKG supplementation improved my biological age in these three ways
IS AKG ANTI-AGING? AKG Supplement improves bio age
AKG supplementation improved three measures of biological age, and has now been permanently added to my longevity hacking stack.
AKG supplementation (also called “Alpha Keto Glutarate") caused a notable stir in the longevity community after a 2021 study in the journal Aging found it improved the biological age of 40 of 42 participants in a small study.
We recently discussed the outcomes of this study with TruMe Labs Co-Founder Yelena Budovskaya, who have now made the biological age measurement from this study available to the general public (via their “TruMe Age Explorer” test).
Naturally, this peaked my own curiosity - could I replicate these results in my own biological age?
After a bit of investigation, it became quite clear that I could. In fact, any one of you reading this could do the same. This post will show you how.
This type of self-experiment is quite straightforward. All you need is a before and after biological age test, a supply of AKG supplement (read our review here) and a scientific approach.
This is, after all, what we love to do here at Longevity Blog - guide our readers to develop their own longevity strategy through self-experimentation.
We have already posted on the reported benefits, basic science, best choice of supply for AKG supplementation in a previous post, so we will get straight into the self-experiment framework and results.
Alpha Keto Glutarate: Experimental framework
Score a 10% discount of high quality, third party tested Alpha Ketoglutarate from DoNotAge with the discount code “longevityblog”.
Dosing of Ca-AKG commenced in November 2022 at 4x capsules of DoNotAge Ca-AKG at 400mg each, for a total of 1.2 grams of Ca-AKG. This was taken with my morning supplement stack, after breakfast.
This dose amount continued for the first 3 months, before increasing the dose to 6x capsules to bring the dose to 2 grams per day.
Dosing remained at 2g/day for the remainder of the experimental period for a total 9 months.
In the 2021 Ca-AKG study from the Journal Aging, dosing was 1g/day for 7 months.
Biological Age Measurements
I measured my before and after biological age with Longevity Blog’s 3x favourite biological age tests (we tested nearly a dozen of them!):
TruDiagnostic’s TruAge (save 15% with code ‘longevityblog’)
TruMe’s TruAge Explorer (save 12% with code ‘longevityblog’)
GlycanAge (save 15% with the code ‘longevityblog’)
Biological age measurements were taken in July 2022 and July 2023, which is my regular annual biological age testing window.
This did mean that 12 months passed between biological age measurements, with only 9 months of AKG supplementation. As you’ll soon see, results were still quite clear.
Blood Measurements
Self-ordered blood tests were ordered through Australian supplier i-screen, who allow you to order and review your own bloods without visiting a doctor.
Blood tests were selected to be very comprehensive. Allowing for the review of immune, liver, kidney function, hormone balance, lipids and more. I carefully chose these tests to have all of the required parameters for the “Phenotypic Age” biological age estimate, providing a fourth type of biological age to test.
Blood tests were closely aligned with AKG supplementation start and ending dates.
A note for your own self-experimenting, you don’t need exact matching between supplement start/end and blood testing. Focus on what’s doable for you - the main thing is that you don’t change any other lifestyle or supplement factors until you’ve completed your follow-up testing.
AKG Self-experiment results
There was a clear improvement in biological age by multiple measures, we’ll work through them sequentially, and then come back for a discussion about interpreting the results.
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The TruAge Explorer test kit. From only $90USD using the discount code ‘longevityblog’.
RESULT: TruMe Age
In July 2022, my TruMe biological age was 38.9 years, or 2.3 years older than my chronological age.
After 9 months of Ca-AKG supplementation, my TruMe biological age dropped to 37.9 years (-1.0 years), however during this period I aged +1 year. This result is 0.4 years older than my chronological age.
Overall, my biological age result improved by 1 year as compared to my chronological age, with an overall improvement of 2 years.
RESULT: Trudiagnostic extrinsic age
TruDiagnostic’s TruAge Complete biological age test kits provide significantly more comprehensive results than any other biological age test.
This includes estimates of both extrinsic and intrinsic biological age, and an estimate of your telomere length biological age.
You can learn more about the differences between extrinsic and intrinsic age in our interview series with Co-Founder of TruDiagnostic Ryan Smith - part 1 and part 2.
AKG supplementation did not have a significant impact on my intrinsic age, however, there was a notable change in extrinsic biological age. Which dropped from 27.56 years (-9 years from chronological age) to 25.10 years (-12 years from chronological age).
I’ve also supplemented with Nicotinamide Mononucleotide and measured biological age before and after using the Phenotypic Age method. Curious? So were we… read the post!
Again, while one year passed, my biological age actually became younger. This time, 3 years of total improvement.
This result is particularly interesting, given AKG’s known role in improving immune system health, but we’ll save that for the discussion.
RESULT: GLYCANAGE
Unfortunately our GlycanAge biological age test was lost in transit and we do not have the after results from this test.
RESULT: Phenotypic Age
In one of our first posts on biological age, we introduced three free ways to estimate your biological age.
Tabulated results across the three tests. Don’t forget that I aged one chronological year over the course of the experiment!
One of these estimates is called Phenotypic Age", and I have now been tracking mine for the past three years, and have been able to find blood tests reaching back all the way back to 2015 to re-calculate (age 30).
After 9 months of AKG supplementation, my Phenotypic Age improved from 30 years old to 27 years old (-3 years). Given that I also aged +1 year chronologically, this is a net result of -4 years.
This biological age estimate is much more sensitive to changes in diet, lifestyle and day to day ups and downs, so we need to consider this result conservatively.
Only once before have I seen a similar improvement (-3.5 years) in my biological age, which was after I self-experimented with NAD boosting supplement Nicotinamide Mononucleotide.
Selected blood results
In the following, I share all blood results that had a significant change over the experimental period, did not have other confounding factors and for which there was scientific research on AKG supplementation that supports a causal link.
All test data presented here is through self-ordered blood test provider i-screen (Australia).
Liver Function
Nov 2022 to Aug 2023 liver markers showed statistically significant improvement. Note that my liver markers are at time elevated because I am an endurance athlete.
Inflammation
Nov 2022 to Aug 2023 high sensitivity CRP, a key marker of inflammation, reached the lowest levels of all time. Even below the levels had 10+ years ago.
LDL-C
Nov 2022 to Aug 2023 saw a 10%+ drop in LDL-C, which, which is significant as it is now at the lowest level I have ever measured. Noteworthy after the March 2021 test, I eliminated dairy from my diet and LDL-C plummeted!
DHEA
Dehydroepiandrosterone sulfate (DHEA) levels are closely linked with cellular energy production, and many important bodily systems are downstream. My levels appeared to climb by 25% post AGK supplementation.
akg supplementation: DISCUSSION
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.
Interpreting the results of a self-experiment is a very important step. It is very tempting to see rdata in results form and try to form a conclusion straight away. To bring in tools from science, we must discuss the results first!
If you’ve ready any of my previous self-experiments, you’ll know that how the self-experiment was controlled is pivotal. In essence, this means limiting as much as possible, any external factors which could ‘confuse’ the results.
When you come to complete you own self-experiments, you need to balance several factors.
First, you need to try the intervention long enough for it to have effect on the variables you are measuring.
In this example, we are looking at biological age changes, which in the case of epigenetic tests like TruMe Labs or TruDiagnostic, take around 3-6 months for effects to be observable.
AKG supplementation has an immediate on cellular energy production, but the flow on effects to the epigenome need significant time (months). In the case of the research study on Ca-AKG and biological age, the results were measured at 7 months of supplementation on average.
My selected period of 9 months allows for enough time for the AKG supplement to imprint on my epigenome and brought it into alignment with my annual biological age testing regimine.
Second, to effectively determine how long the self-experiment will run for, you need also consider controlling other variables which might effect the result.
You’ll want to run the self-experiment for long enough to impact the measurement variables you’re after, but not so long that you cannot control other variables that might impact the result.
Hear from our Founder Nick on biological age testing and how you can change diet, sleep, exercise and stress to improve yours! Read more
In the case of biological age tests, the most influential factors to control are:
diet
sleep
stress
exercise
pollution/smoking
supplements
COVID-19
Well Controlled
In my own case, I have a very regimented lifestyle. I keep to my triathlon and strength training with daily walks (exercise). I sleep a solid 7-8 hours a night, with a consistent bedtime. I live in a rural area with very low levels of air pollution and have not moved in the experimentation window.
No major changes to my exercise, sleep or environmental pollutants were observed.
My diet is a dairy-free, mediterranean-esque diet focused on plant diversity and high protein intake (meat, fish, poultry, eggs, whey protein isolate). I know that this diet works well for me based on my blood tests and biological age data, and I’ve not made any significiant changes to it.
These factors therefore can be considered to be well-controlled, for the purposes of impacting the epigenome.
Not Well Controlled
Stress however, was an unavoidable confounder.
I went through several major life changes over the self-experimentation period, and stress was at times at very high levels, often for weeks at a time. I do believe this negatively impacted by biological age results.
I also contracted COVID-19 in May 2023, which likely also negatively impacted my biological age result, with both experts - Ryan at Tru Diagnostic and Yelena at TruMe Labs suggesting I leave at least two months after my recovery before re-testing. I followed these instructions.
Conclusion: Ca-AKG positively impacted by biological age
Given that the not well controlled self-experiment results would raise by biological age, but that I measured improvements to biological age across three different tests, as well as in several important longevity blood measurements (LDL-C, DHEA, ALT/AST, hsCRP) - I believe there is a solid and clear conclusion.
Ca-AKG supplementation at 1-2g/day positively impacted by biological age.
Note that I do not say ‘reversed’ my biological age, as I do not believe that these tests are able to substantiate that claim.
However, given there was a 3.1 year mean improvement in biological age between these three tests, I can conclude that Ca-AKG will become a permanent addition to my longevity supplement stack.
And through this example, you are now empowered to run the same experiment. This is incredibly important, as if you run the math - taking 1-2g of Ca-AKG per day (using your 10% discount code ‘longevityblog’ at DoNotAge), it will cost you $630 to $1200 USD per year.
This is not a small investment - you want to know the supplement is working for you.
The method and example laid out here can help you answer that question! It did for me!
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
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.
Calcium AKG Alpha Keto Glutarate Supplement Review
What is Alpha Keto Glutarate?
Alpha Keto Glutarate supplementation appears to slow or even improve biological aging. But will it work for you? We dig into the details!
Alpha Keto Glutarate or “AKG” is an important molecule involved in energy metabolism, specifically the Krebs cycle. As its name suggests, it is related to the amino acid L-glutamine, which is produced in the skeletal muscle.
AKG is produced in your body and plays several important roles, including in nitrogen, carbon and ammonia balance.
One very important fact to note about Alpha Keto Glutarate levels in the human body is that they are known to decrease with age, and important cellular functions begin to decrease along with them.
Boosting AKG levels through supplementation may have very significant longevity benefits, but such evidence is in the very early stages of research in humans.
That said, some of that new research is quite exciting - read on.
AKG supplement benefits and safety
AKG supplement use has been around for quite a while and the molecule is very safe to use.
More traditional use of Alpha Keto Glutarate supplementation includes kidney support, intestinal repair, liver support and even the treatment of cataracts.
These uses of AKG are well documented in the scientific literature, with hundreds of studies available for reference.
Alpha Keto Glutarate Supplement Benefits
Boosts muscle growth and athletic recovery
Can help prevent breakdown of muscle during exercise
May delay the onset of fatigue in sport performance
It increases collagen production and may improve bone density
It appears to improve immune function
It collects excess nitrogen and ammonia from the blood, improving detoxification
More recently - it has been linked to specific longevity benefits, such as improving biological age (more on this shortly)
Its role in gene expression (epigenetic) and cell signalling is in the early stages of research, but it is clear that AKG helps preserve youthful cellular function
Alpha Keto Glurarate Safety
Is Alpha Keto Glutarate safe? Are there side effects?
Yes, very much so. In fact, we were able to find no known adverse effects from AKG supplementation for doses up to 2g per kilo of bodyweight (that’s much more than you’ll need to take!).
How much AKG supplement should I take?
This entirely depends on your reason for taking an AKG supplement in the first place.
Here are three examples!
You are an athlete looking to improve sports performance or recovery. You’ll supplement anywhere from 1 to 15 grams per day. You can take it before exercise to limit muscle breakdown during the activity. Or you can take it afterwards to improve recovery.
As a bodybuilder, your goals are to increase muscle mass. You’ll likely be taking Arginine Alpha Ketoglutarate (AAKG) and doses will vary from 3 to 10g prior to your hypertrophy workouts.
Nick has now completed his own self-experiment with Ca-AKG, dosing at 2g/day. Read about how to replicate this yourself and see his results in detail here!
As longevity enthusiast and wellness biohacker (that’s us!), you most likely want to see if you can improve your biological age with Calcium AKG supplementation. At this stage, we have limited evidence of the dosing protocols, with one study using 1g/day (with impressive effects on biological age!).
The remainder of this post will focus through the lens of the longevity biohacker. However, our chosen supplier of Calcium AKG + our 10% discount may still be valuable to you as an athlete or bodybuilder, so scroll on ahead anyway!
Calcium Alpha Keto Glutarate for Longevity
To understand the applications for Calcium AKG for ‘anti-aging’ / longevity benefits, there are three key milestones to review
50% improvement in lifespan in C. elegans after AKG supplementation. Source: Nature
AKG supplement and Longevity in Worms
The first is a foundational research study in 2014 which grabbed a lot of attention, as AKG supplementation increased the lifespan of C. elegant (nematodes, a type of ‘worm’) by nearly 50%.
The primary mechanism for doing so was believed to be the inhibition of ATP synthase and TOR (the worm version of the mTOR pathway).
AKG supplement and Longevity in Mice
Secondly, a follow-up study in 2020 looked into the Calcium Alpha Ketoglutarate form of AKG in mice. In this study, middle aged mice received an AKG supplement, as as result male mice lived 10% longer and females 20% longer.
Observed benefits of Calcium Alpha Keto Glutarate supplementation in mice, who lived up to 20% longer. Source: Cellular Metabolism
The mice had fewer grey hairs and remained stronger and less frail than their peers. A key mechanism of action was believed to be a widespread reduction in inflammation (“inflammaging“ is one of the primary ways in which humans lose function and resilience with age).
AKG supplement and Longevity in Humans
Third, and most importantly, a 2021 study in the journal "Aging" made a startling discovery.
Across a cohort of human trial lists taking 1g/day of a Calcium AKG supplement for approximately 7 months - there was a median improvement in biological age of 8.5 years.
This is a very significant change/result! To put this in perspective, our Founder Nick has only been able to improve his biological age by 3 (read here) to 6 years (see here) and to date he has not been successful in improving his epigenetic biological age at all.
By the way….
The biological age test used in this Ca-AKG supplement study is the TruMe Age Explorer test.
This epigenetic biological age test kit is available to try at home for only $103USD when you use our discount code ‘longevityblog’ to save 15%.
If you order two kits (essential for doing before & after self-experimentation…) the cost per kit with our discount drops to $88USD.
When you consider that alternative epigenetic age tests costs $300-$500USD, this offer looks pretty appealing!
We’ll be interviewing Co-Founder Dr. Yelena Budovskaya in an upcoming post to discuss how this test works in more detail!
It’s the most affordable test on the market and is very fast and easy to complete.
AKG Supplement Review
AKG chemical structure before bonding with either L-Arginine or Calcium. Image Source: Pubchem
Given this encouraging result, a natural follow-up question from the longevity enthusiast is of course ‘where can I get myself some AKG??”.
We were of course curious ourselves.
There are two primary forms of Alpha Keto Glutarate supplements.
The first is Arginine Alpha Ketoglutarate (AAKG). In this formulation, AKG is bound to the amino acid L-arginine. L-Arginine is a good choice as it is involved in nitric oxide regulation and dilates blood vessels. This delivers more nutrition to the skeletal muscle and can increase insulin by up to 10-15%, meaning more muscle growth.
Research studies on Alpha Keto Glutarate over time
The second formulation is Calcium Alpha-Ketoglutarate. And if you’ve been reading closely, you’ll realise that this is the form of AKG supplement which has shown longevity benefits in both rodents and humans. By using calcium, the absorption of AKG in the small intestine is improved.
This is important as only 20% of oral AKG supplement intake makes it to the liver and then into the bloodstream, where its beneficial effects can take effect.
Given the improved absorption and the direct connection to the biological age improvement, we think that it will be pretty clear to you that a Ca-AKG supplement makes more sense for the longevity enthusiast.
What is the best AKG supplement?
By narrowing the search to a Calcium Alpha Keto Glutamate supplement, the list of options for supplying yourself with Ca-AKG for your own self-experiment narrows considerably.
As with any self-experiment, you’ll want to only add a Ca-AKG supplement to your stack and watch changes over time. One notable exception is taking a B6 vitamin (or B-complex) supplement along with it to increase absorption.
Reviewing the available Ca-AKG supplement options then narrows further, as we are only considering a pure formulation. Longevity Blog was able to identify approximately 3-4x options with global shipping and sufficient reputation for quality assurance.
Nick is preparing a video series on Ca AKG supplementation and his self-experiment to reduce his epigenetic biological age.
Our recommendation: Alpha Keto Glutarate Supplement - DoNotAge
Our recommendation (which is not entirely unbiased - read more here) is to purchase from DoNotAge.
This is partially based on our intimate knowledge of the manufacturing process, including products quality and purity.
It also based on our ability to reduce your costs (part of our goal at Longevity Blog is to help stretch your longevity budget further!).
Working the math, if you select the bulk 366 capsule option, which qualifies for free shipping in the United States, DoNotAge’s Ca-AKG costs $1.92/USD for a 1200mg dose (three capsules).
This drops to $1.72USD per 1200mg dose with 10% discount code ‘longevityblog’.
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with DoNotAge, we are pleased to offer a 10% off coupon code for our readers. This applies to all DoNotAge products, not just Ca-AKG.
Use the code longevityblog at checkout to save!
CAN CALCIUM ALPHA KETO GLUTARATE REVERSE BIOLOGICAL AGE?
We’re not huge fans of calling it ‘reversing’ biological age, but this is the most common search term used by people looking for this answer.
Instead, we want you to think of biological age as a subjective number that you can improve.
After all, our Founder Nick has improved his biological age many times, using different biological age tests and approaches (read here and here, for example).
Here we are yet again - wanting to know, can a longevity supplement improv your biological age?
There is only one way to find out - it’s self-experiment time!
Soon, we’ll reveal the dosing strategy and before and after testing approach required to put Ca-AKG’s claims to the test!
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.
Mitopure Review - Does this Urolithin A supplement actually work?
Reviewing Mitopure Before and After - Urolithin A Supplement Self-Experiment
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Use the code ‘longevityblog’ to save 5%
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We review the Urolithin A supplement Mitopure. We review Mitopure through our favourite approach - self-experimentation to answer - does Mitopure actually work?
Urolithin A supplementation is grabbing some serious attention in the longevity technology space. With its purported benefits in mitochondrial rejuvenation, it appears to be a promising intervention into the known age-related decay of mitochondrial health over time.
Beyond its proven positive impacts on mitochondria, Urolithin A is showing promise in reducing the incidence and intensity of several types of cancer, including prostate, pancreatic and colon cancers. It also appears to have powerful effects in healing the gut barrier and may help support a healthy immune system.
Urolithin A is a by-product of the digestion of ellagitannins, which are found in certain foods, including raspberries, walnuts and pomegranate. However, only 20% of people have the right gut flora to covert ellagitannins into urolithins (more on this shortly).
This is why there are likely many benefits to Urolithin A supplementation.
In this post we’ll review:
what is the best source of Urolithin A?
who makes Mitopure and is it legit?
how can you know if Mitopure will work for you?
our Founder Nick runs a self-experiment with Mitopure
The Best Urolithin A Supplement is Mitopure
If you’re interested in self-experimenting with Urolithin A, don’t go searching for “Urolithin A supplement Amazon” hoping for an alternative to Mitopure.
Mitopure is currently the *only* and *best* Urolithin A supplement available. Putting your hard earned cash anywhere else at this stage will only lead to disappointment, as our review of the alternatives has not found anything else worth mentioning (as of late 2022).
Why is this the case? Simply put - no other supplement is actually isolating Urolithin A. What you are getting instead are pomegranate extracts. However, if you do not have the correct gut flora, pomegranate extracts will not convert to Urolithin A in your digestive tract. That’s your hard-earned money wasted!
If another source of Urolithin A supplement becomes available, we’ll be sure to share it with you.
Over the course of the next few paragraphs, we’ll explain to you in additional detail why Mitopure is your best Urolithin A supplement option (and how to know if it will work for you).
Who Makes Mitopure?
First, if you would like to understand the history behind this Urolithin A supplement and its path to becoming a consumer product, you can check out our interview with Amazentis CMO Federico Luna. He details the decade long research effort that Amazentis put into dicovering and developing a Urolithin A supplement.
Who are Amazentis? They are a Swiss pharmaceutical company that was founded by scientists, doctors and entrepreneurs who wanted to create a new class of nutrition supported by the rigor of research you typically only find in biotechs that are solely developing drugs.
To bring Urolithin A to market, they founded Timeline Nutrition, who are the makers of Mitopure.
Is Mitopure Legitimate?
Yes! Mitopure is about as legitimate as it can possibly get in the supplementation space.
Timeline Nutrition was founded by a highly respected phamarceutical company that needs to be ensure its reputation is spotless. They then branded the Urolithin A supplement used in their research studies under the brand name “Mitopure”.
Now consumers have access to the exact formulation of Urolithin A which has been producing impressive results in clinical research studies and has proven safety and efficacy.
Furthermore, Amazentis are now putting millions of additional dollars into research efforts to study and better understand the impacts of Mitopure in humans, particularly in age related decline of muscle quality and into its benefits for sport performance (for example, their collaborative relationship with the American College of Sports Medicine).
You’d be hard pressed to find another longevity supplement with such a reputable background.
How much does Mitopure cost?
Mitopure Urolithin A supplement in sachet form. It is also available as a softgel.
You won’t find a better deal on Mitopure than through our 5% discount code (‘longevityblog’) and purchasing directly from Timeline Nutrition on a subscription. That’s the most cost effective way to get your own supply for self-experimentation.
In part two of our interview with Amazentis CMO Federico Luna, we worked with him to break down the costs of Urolithin A supplementation.
We found that Mitopure costs about 50-60% of what it would cost to get an equivalent amount of Urolithin A from pomegranate juice (you’d also have to drink 1.3L of it each day).
The cost of Mitopure is between $2.50 to $4.00 per day, dropping to $2.35 to $3.80 per day with our discount code ‘longevityblog’. The lower cost options are for longer term subscriptions (up to 12 month supply), which save you progressively more as you extend your supply.
We have found that 1-2 months supply is effective for testing before and after to see if Mitopure works for you (read on for those details).
Once you have decided on your volume of supply. You’ll of course want to be able to test and see - does Mitopure actually work? This is where Longevity Blog content really starts to shine! It is self-experiment time!
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Mitopure review - is it worth it? We self-experimented to find out
In this self-experimentation, as per usual we had our Founder Nick set off on a detailed self-experiment to test Mitopure before and after.
However, in a Longevity Blog first, we have also invited members of our readership to participate in self-experimentation as well!
In an upcoming post, we’ll also share the results from both a high performing amateur cyclist (Aaron) and an ironman triathlete (Claire). Be sure to subscribe to get notified when we post their results!
Starting Point: Do your gut flora produce Urolithin A?
The answer to this question is paramount. If you are one of the 20-30% of individuals who can produce Urolithin A from the ellagitannins in foods (pomegranate, walnuts, berries, etc), then you are much less likely to have a measurable response from supplementing Urolithin A.
Nick takes the “Mitopure Challenge” to see if he produces Urolithin A from Pomegranates
Nick undertook the ‘Mitopure Challenge’ to see if he was a natural producer of Urolithin A (no need to supplement) or if he would benefit from taking a Urolithin A supplement.
In this experiment, Nick drank 300ml (11oz) of fresh pomegranate juice and then gave a few drops of blood via finger prick the next morning.
On the following day, he took 500mg of Urolithin A supplement Mitopure and repeated the blood test process. This blood was sent back to Timeline where they analysed it to see the concentration of Urolithin A Glucuronide.
The result? Nick was not a producer of Urolithin A (at left in image). His gut flora did not produce Urolithin A after drinking pomegranate juice.
However, there was a significant increase in Urolithin A in his bloodstream after taking 500mg of Mitopure.
At left (zero), Nick’s Urolithin A Glucuronide levels after drinking 300ml of pomegranate juice (11oz). At right, after 500mg of Mitopure. This result shows that Nick was not naturally producing Urolithin A through his diet and that supplementing with Urolithin A would be likely to provide him with measurable benefit.
Measuring Urolithin A Supplement Benefits
As we look at the research into Urolithin A, most of the results thus far have focused on muscle strength as the primary measure of performance improvement. However, several studies are underway to look at Urolithin A benefits and safety in athletes.
While the results from these works have not yet been published, we can expect them quite soon. Naturally, given the exceptional role of mitochondria in athletic performance and the primary mechanism for Urolithin A’s health benefits being mitophagy, we can expect that athletic performance is an excellent data point for establishing the efficacy of Mitopure.
“What we’ve shown is Urolithin A acts on the mitophagy pathway... 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 ”
But not just any exercise - we need to look to specific types of exercise which are repeatable, well controlled and which place significant demand on mitochondria.
Given these requirements, Nick decided to use running interval workouts as his primary before and after data point.
This type of exercise is energetically demanding, repeatable and relatively well controlled (if we use the same workout).
It entails running at a very high intensity, where mitochondria are under very high demand for energy production.
If Urolithin A really does trigger mitophagy, then Nick’s older less functional mitochondria should be recycled into new more efficient mitochondria, and this should be observable as an improvement in his athletic performance.
In addition to running data collected from Nick’s Garmin Fenix 6 and HRM Pro (Chest-strap heart-rate monitor), Additionally, a detailed blood panel was collected using the i-Screen Sport Hormone Check (self-ordered blood tests available in Australia).
Mitopure Before and After Results
Nick’s training load from mid-June to mid-July. Relatively light and recovery focused.
The self-experiment begins as Nick enters the triathlon ‘off season’ where he is not running interval workouts. He travels to the United States for 6 weeks starting in mid-June 2022 and has only intermittent training opportunities; while he is consistent with training his volume/load is much lower (see image) than it was in the preceding 6 months.
Nick’s training load from mid-August to mid-September. It was gradually picking back up, but consisted mostly of ‘base training’ in August and did not train running intervals in August (leading up to the test date).
Nick begins Urolithin A supplementation at the start of July (training load remains low) at 500mg/day and returns to Australia and regular triathlon training at the start of August. At the end of August, he re-tests the VO2 max pyramid workout.
As his first proper interval workout in nearly three months his expectations were low. However, as he began the workout, he was very surprised by how he felt.
Let’s take a look at the data and let it do the talking.
Before - Interval Run
Data from Nick’s ‘Before’ running interval workout. Click to zoom. Blue is running speed and red is heart-rate.
The before and after running test are a VO2 max pyramid. This type of workout is structured such that you add one minute at your target pace for each interval.
There are 7 intervals. The first is 1-minute, the second is 2-minutes, then 3-minute, 4-minutes and then back down the pyramid (3min, 2min, 1min) each with two minutes of recovery in between.
There is also a warm-up with some 30 second ‘builds’ at the beginning where your work up to your target pace to get your body ready to perform.
In the ‘Before’ test, Nick had a target pace of 4:10-4:15/km, which he was able to hold for the first 3 intervals, but not for the fourth interval.
His heart-rate peaked at 187bpm (Nick’s maximum HR is 210bpm) on the third interval. Nick reported that he was unable to finish the full pyramid after failing to complete the fourth interval at pace. Simply put, he ran too fast and built up too much lactate and couldn’t hold the target pace.
After - Matched Interval Run
Data from Nick’s ‘After’ running workout. Click to zoom.
At the end of August, Nick completes the ‘After’ test, which is the same structure as the first.
This time he was able to complete the work out at the target pace of 4:10-4:15/km. Additionally, he did so at 5-7% lower heart-rate than in the ‘before’ test, running at 175-180bpm.
He also found he had to moderate his pace as he was running the intervals too quickly at the start (3:50/km pace).
This was due to a change in relative perceived effort (RPE) where faster speeds felt easier than they did previously.
There certainly appears to be a significant change in Nick’s performance. So let’s discuss.
Discussion: Does Mitopure Urolithin A Supplement Work?
Before we jump to any conclusions at Longevity Blog - we have a thorough discussion. Sure, the numbers appear convincing, but let’s make sure we consider the results carefully (and scientifically).
There are some potential confounding factors to consider in answering the question, did Urolithin A supplementation boost Nick’s athletic performance?
First - training. It would be expected that Nick’s ability to hold a given running pace would improve over time as he is training. Could he have simply gotten 5-7% faster from his off-season training?
As we mentioned already, Nick wasn’t running any interval workouts during the intervening period. In fact, he had much lower training load while he was travelling.
In run training, it is generally accepted that if you want to run faster, you have to train by… running faster. This is what running intervals are for, they allow you to accumulate training time at a faster pace so that you can hold that pace for longer.
Nick was not doing this. It is safe to say that training was not a factor.
Second - reduced training load; could it be a factor?
It is possible that the several weeks off provide Nick with ample recovery time and that he was able to re-engage the interval workout with ‘fresh legs’ and hence why he was able to perform so well.
However, Nick reports that his ability to run these interval workouts has been sustained as he picked back up his training load in September and October. As he has again become fatigued and picked his training load back up by 3-4x what is was in June, he can still run at this pace for his running interval workouts.
It does not appear that being ‘fresh’ and well rested is why Nick was able to run faster for longer in the ‘After’ workout.
Third - the one off nature of the analysis; Nick could have had a bad day in the ‘before’ workout and a ‘great day’ in the ‘after’. Was this the case?
Our response to the ‘second issue’ about re: training load addresses the latter. Nick’s performance gains have been sustained as he has continued with Urolithin A supplementation. In fact, he can now run 3:50/km intervals for 4-5 minutes at a time and is running a 20-minute 5km race time (that’s 4:00/km for 20 minutes).
As for the ‘before’ data having been a ‘bad day’ as a one off, we searched through the Strava and Garmin case files. We found two matched workout runs of Nick’s from before Mitopure supplementation. In each, we observed the same inability to hold the target pace across the whole workout.
Nick at the Byron Bay triathlon in May 2022. He loves the run leg… is Mitopure helping him improve his times? Evidence suggests - Yes!
Mitopure Review - Conclusion: Nick is running faster after Urolithin A supplementation
In our view, the data support a significant improvement in Nick’s interval run times after supplementing 500mg of Mitopure Urolithin A.
This improvement has not only been sustained, but Nick’s running times continue to quicken as he continues supplementing with Urolithin A.
Anecdotally, Nick reports lower heart-rate at equal pace on his easier runs as well. He has also seen a 20% improvement in his cycling FTP (functional threshold power), but none of these results have been well controlled or directly verified.
His fellow triathlon club teammates have also noted his rapid improvement!
Will Mitopure Work For You?
So, will Mitopure work for you? We can’t tell you the answer. There is only one way to find out! Run your own-self experiment!
Use “longevityblog” at checkout to save 5%
We have two Longevity Blog readers who are trying their own Mitopure self-experiment (Aaron and Claire). Will you join them? Let us know, you just might be featured in the next Longevity Blog post!
Until then, Live Long!
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.
One Skin Review - Self-Experiment Before and After Results with OS-01
Reviewing One Skin OS-01 - Does it really work?
Hey there, and welcome to Longevity Blog. Questions like these are what we obsess over.
We’ve previously introduced our readers to the topical supplement OS-01 from OneSkin, a longevity technology company with a new approach to skin health.
OS-01 gets it's name from the proprietary peptide discovered by the One Skin research team, which has been shown to turn on cellular repair mechanisms in the skin - meaning it is actually fixing things like UV damage, not just covering them up. You can read about the science in more detail here.
If you’re one of those impatient folks looking for ‘the answer’ - for our Founder Nick’s face, it was a yes it does work! And we can show you how to test it on yourself, keep reading.
For Nick, OneSkin OS-01 reduced his aesthetic age by 7 years.
Early results from beta testers and research studies have been very promising - but of course the primary question for you remains - will it work for me? Does OneSkin OS-01 really work?
As with any longevity technology, asking and answering this question is very important.
After all, if OS-01 really can “reduce your skin’s biological age” as the company claims, then perhaps it really is worth shelling out $120/bottle.
(By the way, that’s only $102/bottle when you use ‘longevityblog’ at checkout to save 16%).
If the product really can reduce your skin’s biological age, then you might just make this investment.
But, of course, with any supplement, you’d need to know with high confidence that it is working. After all, even with a subscription, this decision could cost you upwards of $1000/year.
So - the question is, how do you know with certainty that OS-01 is working?
That’s exactly what Longevity Blog loves to do - help you figure out what works for YOU.
If that’s your jam too, please read on.
How to Tell if OneSkin OS-01 Really Works
As we covered in our interview with OneSkin CEO and Co-Founder Dr Carolina Reis, there appears to be some real science behind their biological age reversal claim.
More relevant to the question of reviewing One Skin OS-01’s effectiveness, we also asked Dr Reis how can you test OS-01 on yourself and know if it really works?
Here’s an extract of part two of our interview, where we dug into this topic area:
Will OneSkin OS-01 Work for You?
Longevity Blog:
How long should our readers run on OS-01 self experiment? What is a long enough period to evaluate before and after?
Carolina Reis: 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.
… We continue to search for a method that can be quantitative and we still don't have it, unfortunately, to offer to consumers.
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.
… The clinical trial level of rigor is six months. We've heard from users benefits can be seen after three months.
OneSkin Before and After Pictures - Surely We Can Do Better?
If you’re scientifically minded like us, you might find this answer somewhat unsatisfying.
How many of us are really skilled enough at using a camera, pointing it at ourself, getting the angles and lighting done correctly/consistently and come away with photographs that can really see the often subtle differences in skin health that might occur over months at a time?
And while there is promise in some of the future ‘quantitative’ methods for measuring skin age directly, that technology is not here yet.
Surely there could be a better way?
Well, our friends, we did our homework, and it turns out, there is a better way.
And if you ask us, it’s pretty damn cool.
Review OneSkin OS-01 Effects on Your Skin with a Visia Scanner
Nick getting his follow-up Visa scan at NextHealth LA.
To conduct an effective self-experiment with any skincare regime change, we recommend that you locate some nearby skin clinics and ask them if they operate a Visia Scanner.
It may take a few calls, but these devices have become very common in such clinics.
We’ve previously covered this technology in earlier posts, and we are a big fan.
Not only does this system provide solid, repeatable quantifiable metrics (pore size, skin redness, texture, etc), but it also is relatively cheap to operate (often a clinic will do this for you for free as a part of a skincare consultation).
A Visia scan also will provide you with the “TruSkin Age” of your face, which we have deemed your ‘Aesthetic Age’ (analogous to your biological age), revealing how old you look, based on a pretty comprehensive algorithm.
While this TruSkin Age is a proprietary algorithm and we cannot know exactly how it works; Campbell Scientific have shared the eight most influential metrics which go into the TruSkin Age calculation (we share those below).
Self-Experiment Guidance
If you’re interested in giving this a try, we suggest the following:
Keep your skincare regime unchanged except for adding OS-01 to your protocol (control your self-experiment)
Get both before and after scans from a Visia unit at a nearby skincare clinic
be sure to use the same ‘prep’ routine before each scan
do with with a clean face
use the same products you used in the before image in the after image
Run the experiment for at least 3 to 6 months
Compare the results, focusing on both:
the TruSkin Age
wrinkles, texture, spots and UV spots (as reported by Visia unit)
What are you looking for? How do you compare the results?
Well the simple answers is that if your TruSkin Age improves, whatever you’re doing is working.
But of course, we love the details, so we’re going to walk you through an example looking at the four most important skin metrics for an OneSkin OS-01 self-experiment.
One Skin OS-01 Results with Pictures
Our Founder Nick absolutely loves to be a guinea pig for longevity technologies of all sorts.
He was very enthused to try out OneSkin OS-01 using the above framework, where he applied OS-01 daily to a clean face before bedtime with approximately 98% compliance over 5 months.
What did he find? Shockingly, according to the Visia Scanner OneSkin OS-01 reduced his aesthetic age by 7 years.
Most valuably, the Visia scanning unit was not with out direct justification for this drastic improvement - and we’re going to look into the details as to what changed to create this improvement.
NOTE: Moving ahead, many will note there is a slight variation in Nick’s face angle in the before and after images. We will discuss the possible impacts of these on each metric.
Visia Scanner Metrics as Reported by Campbell Scientific
Visia scans report on 8 key metrics, which are used to determine your TruSkin Age and track the impact of skin care treatments over time.
Some of these metrics are more responsive to a given intervention than others. So it is important to know which of these metrics to pay attention to when you’re self-experimenting.
Using abridged descriptions from the Campbell Scientific FAQ page and bit of input from skincare specialists, we decided to track four metrics in this self-experiment with OneSkin OS-01:
Wrinkles : Wrinkles are furrows, folds or creases in the skin, which increase in occurrence as a result of sun exposure, and are associated with decreasing skin elasticity. This skin feature has the greatest variability from image to image as it is highly dependent upon the facial expression of the client.
Texture: Texture 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.
Spots : Spots 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.
UV Spots : UV spots occur when melanin coagulates below the skin surface as a result of sun damage. UV spots are generally invisible under normal lighting conditions.
We’ll now progress through the results from each and discuss. In each a ‘lower’ score (number below the image) is considered ‘better’ with respect to the TruSkin Age and overall skin health.
Does OneSkin OS-01 Reverse Wrinkles?
“The change in the wrinkles around my eyes was my biggest visual observation,” reports Nick. “I’ve actually looked in the mirror and said ‘Wow’ out loud. I really feel as if I turned back the clock with my eye wrinkles”
But does the Visa scan agree? Emphatically yes. In the before image, a significant number of individual, smaller wrinkles around the eyes were detected (noted in green).
In the after image, Nick’s skin is relatively unwrinkled.
While there was likely an impact on the wrinkle algorithm from change in facial angle, it is very unlikely that this the source of such dramatic improvement.
The biggest impact of the difference in before and after facial angle is the change in the looped area (blue line) closest to the nose/inner eye. However, even if we removed the entire region below the eye due to this effect, there would still be a very significant change in wrinkles along the outer eye/upper check junction.
This individual result is also supported by clinical evidence (see accompanying image from OneSkin), where ‘in vivo results’ (in real humans) showed reliable improvements in skin elasticity & less wrinkles.
We conclude that improvements in Nick’s skin health from OS-01 were the driving force for this significant result and big change in the 'wrinkles’ category.
Does OneSkin OS-01 Improve Skin Texture?
Moving onto our next metric, we analyse skin texture.
Improvements in skin texture and smoothness after topical application of the OS-01 peptide have also been observed in the clinical setting. Source: OneSkin
Based on our interview with Dr Reis in February, we’d expect there would be observable improvements in skin texture.
Particularly given the noted impact of the OS-01 peptide on this parameter in the clinical setting (see image at right).
This likely connected to the observable improvements in the overall skin barrier, as discussed in our interview with Carolina.
“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.”
Once again, in the before and after scans, there are very significant differences.
In this metric, the overall score for texture is less significant than the total number of different blue and yellow dot pairs. These are the “peaks (yellow) and valleys (blue)” on the skin surface.
We observe a dramatic improvement in skin smoothness/texture after 5 months. While there may have been impacts from the slightly different imaging angle and small variations in the facial scanning region (the blue loop around Nick’s cheek), neither could account for such a large difference.
To us, this looks like OS-01 clearly improved skin texture for Nick.
Does OneSkin OS-01 Improve Skin Spots?
A self-experiment by longevity blogger VivaSparkle, where OneSkin OS-01 reduced the appearance of age spots over the course of 3 months.
Age spots are one of the most notable and widely recognised signs of skin aging.
Such ‘spots’ are detected by the Visia scanner, which is searching for brown/red skin ‘lesions’ (including moles and freckles) and also hyper-pigmentation.
We know from other anectdotal sources and early users of OneSkin that improvements in ‘age spots’ have been notable. One such example is from longevity blogger VivaSparkle (shared at right).
For Nick’s before and after results with OneSkin, there is once again a pretty clear signal.
While there are slight variations in the scanning angle and the looped region of analysis (blue line), the changes in the density of detected age spots are quite clear.
There are fewer age spots per unit area on Nick’s cheek, jawline and nose.
Based on these results, we believer that OneSkin OS-01 has reduced the number of age spots on Nick’s face after five months treatment.
Can OneSkin OS-01 Reverse Sun Damage? UV Spots
Lastly, we review the before and after results for UV spots.
These spots are picked up using a special UV imager and a flash of UV light, to make these spots visible (they are invisible to the naked eye).
They form as a result of UV damage, as the melanin coagulates beneath the skin surface, and will eventually lead to visible damage at the skin’s surface and are a sure sign that collagen is also being degraded.
As Dr Reis pointed out, this is one of the primary drivers of skin aging, and in fact, OneSkin uses UV radiation in the lab to artificially age their 3D human skin equivalents.
Simply put, UV radiation is nasty stuff and it really damages your skin.
One of the chief claims of the OneSkin team is that OS-01 is turning on the body’s repair mechanisms for exactly this type of damage.
However, we did not observe a clear result with UV spots before and after in this self-experiment.
While there does appear to be a decrease in the density of UV spots before and after, and the (score) has dropped in the after image (by over 20%), we do not believe the results are conclusive on this one.
In short, there may have been improvements in UV damage to Nick’s skin, but due to the small change, variation in scanning area/angle, it is not possible to conclusively determine this.
Will You Self-Experiment with OneSkin OS-01?
Nick confirms that after these results, he is most certainly going to continue using OS-01 daily.
And now, with this self-experiment complete, he has high confidence that the costs of doing so are well worth it.
This is precisely why we aim to support our readers with examples on how they conduct their own self-experiments to see what longevity technologies work best for them.
Will you conduct your own test with OneSkin? If so, we’d love to hear from you!
Don’t forget our discount code (“longevityblog”) so you can save 15% on your order.
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!
Note: You must use the above link for the discount code to be applied to your 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.
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…
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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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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 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.
Increasing Plant Diversity Improves GlycanAge Significantly - A Self-Experiment
First things first - we have a 15% discount code available for the GlycanAge test - ‘LONGEVITYBLOG’.
Now go run your own self-experiment!
Glycan Age Test Self-experiment Results
In a series of recent posts, Longevity Blog has been investigating glycans and their many important roles in the body.
There is much to learn, but the key takeaway is that they play an informative role to the immune system by ‘tagging’ which of the many foreign molecules in the both are friend and which are foe.
We’ve some ideas on how you might improve your GlycanAge - by eating more types of plants! Read on for more!
If you’re across the basics of how the immune system works, you’ll be aware that inflammation is a sign that the immune systems is activated.
And while this can be highly valuable for enacting repair of specific areas of the body (e.g. damaged tissue), it is also a destructive process (e.g. tear down and rebuild that tissue).
As we age, levels of chronic inflammation rise, both as a result of and a cause of the aging process.
In your quest to maintain your ‘youthfulness’ and achieve longevity, monitoring and improving levels of inflammation in your body is highly important!
However this has not always been easy. There are many ways to measure inflammation in the body - which to choose? How to improve it?
It turns out, there is a simpler answer - don’t track the result of inflammation, instead track the molecules which signal - should inflammation be ‘on’ or ‘off’?
That line of thinking brings us to glycans and specifically the GlycanAge biological age testing kit.
In this post, we’ll review the results from our Founder Nick’s GlycanAge self-experiment. For the nitty-gritty details on the how & why the experiment was conducted, including the hypothesis and scientific framework, be sure to read that post first!
Read on for a few basics, and then a deep dive into the results.
Self-experimenting with diet to inform the immune system
Hey everyone, Nick here! I’m excited to share with you that I was able to improve my GlycanAge by 6 years in just 3 months, with a specific dietary change.
That change? Eating at least 30 different plants per week.
This self-experiment was completed in effort to improve a GlycanAge that was already quite favourable (30 yrs for a 35 yr old) in an individual who was already ‘doing all of the right things’ with diet, exercise, sleep and stress.
From my perspective, -5 years just wasn’t quite good enough. I was convinced I could improve further, as I’d achieved much younger biological age by other measures, and I like a good challenge!
To complete this self-experiment I dutifully designed and tested a specific hypothesis, which was:
“By programming the immune system with a diversity of plant information (local & organic where possible), chronic inflammation will be reduced as the immune system learns more about what is friend and what is foe, leading to an improvement in the Glycan Age”
Let’s briefly talk about why adding more plants to the diet could be reasonably expected to improve GlycanAge and then take a look at the evidence which shows it worked.
Why would 30 plants per week improve glycanAge? The basics
Of course I suggest you read the introductory post, which will offer you much more detail, but here is the main line of reasoning why eating a diversity of plants is likely to improve your GlycanAge.
Delicious veggies from our local farmers market. Full of environmental information just waiting to program your immune system. Eat me!
The immune system is constantly monitoring what you eat - deciding what should and should not be allowed into the bloodstream.
This surveillance occurs in the small intestine at your “intestinal epithelial cells” (IECs) which act as a filter, whereby nutrients, electrolytes, water and beneficial bacteria are allowed into the bloodstream (while the ‘baddies’ are not)
The immune system that is supporting the IECs with this ‘filtering' step is learning what is good and what is bad through the diet you eat
This effectively means that your diet is information about your environment
The diet is then responsible for telling the body, through a diversity of food and organisms, what is ‘friend’ and what is ‘foe’ - and it does this through partnership with glycans
Thus the hypothesis:
When you don’t eat a diverse diet your immune system receives less information = more inflammation (and higher GlycanAge)
However, the opposite is also hypothesised to be true: more information = less inflammation (and lower GlycanAge)
Did it work? Experimental results
The results from this self experiment are provided through the GlycanAge online dashboard, which delivers a biological age result, but more importantly, a breakdown of the three most important glycan indices.
These indices summarise the 24 glycan types which regulate inflammation in the body, and are broken down in GlycanAge test results as follows:
G0 are glycans without galactose, which are the most proinflammatory. These are represented by the Mature Index.
G2 are glycans with two galactoses, which are suppressing inflammation. These are represented by the Health Index.
GS are glycans with sialic acid, which also suppress inflammation. These are represented by the Youth Index.
Result: GlycanAge improves by 6 years
I am presently 35 years old. My GlycanAge at the start of the self-experiment was 30, an encouraging result. After eating 30+ plants per week for 3 months, my GlycanAge further improved by 6 years, to a value of 24.
If you’re interested to understand a bit more about how this biological age estimate works, you can read our interview with glycan expert Prof. Gordan Lauc.
One very important question that we asked Prof. Lauc was about the importance of the absolute value of biological age versus the relative changes that occur over time.
“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. ”
My GlycanAge at the start of the self-experiment.
My GlycanAge at the end of the 3 month experiment.
Result: glycan indices improve across the board
One aspect of the GlycanAge test kit that I really like is that they give me direct access to raw data, a summary PDF report and insightful indices which breakdown the biological age estimate further.
Not many biological age test kits will offer you this level of detail, and it provides an important layer of additional insight into why a given self-experiment worked/didn’t work for improving biological age.
Intriguingly, the self-experiment resulted in across the board improvements in these indices. The changes in the % relative to my peers (percentiles) reveal this in a straightforward way.
For example, the ‘Health - G2’ index improved by 0.11. What does that mean? My result is now better than 60% of others in my age group, whereas before it was only 49% (a below average result).
The three major glycan indices at the start of the self-experiment.
The three major glycan indices at the end of the self-experiment.
Improving GlycanAge with diet: Discussion
Interpreting the results of a self-experiment is very important. We cannot simply look at the data in results form and make a conclusion. In the spirit of science, we must discuss them!
The most important aspect to discuss here, is how the self-experiment was controlled. In essence, this means limiting as much as possible, any external factors which could ‘confuse’ the results.
Importantly, we need to examine any changes in the four main drivers of GlycanAge results. As Professor Lauc outlined for us in his in-depth Longevity Blog interview, these are: stress, sleep, exercise and diet.
Let’s briefly review each.
Controlling Diet
I kept a simple list organising plants I ate into groups of 10 for each week of the self-experiment. This was done in the ‘notes’ app on my iPhone and was very easy to manage.
In our experiment we turned the ‘diet knob’ in a very specific way. By introducing the primary experimental change of eating 30+ plants per week.
First of all - compliance. I can confidently report that I was fully compliant over the 12 week period of experimentation.
In no week did I eat less than 30 different plants. I ate as many as 40 different plants and as few as 31 different plants.
I did not change my dietary protein, carbohydrate or fat ratios or overall intake of calories.
Inevitably, I did eat more soluble fibre due to increased plant diversity, however, I was already eating many organic vegetables and select fruits to begin with.
I just was not eating many different types, instead favouring about 10-15 different plants which I ate repeatedly.
It was as a fun challenge to find new plant foods to try! It resulted in my whole family eating more plants as well - an added bonus.
Controlling Sleep
As any good longevity focussed biohacker, I’m quite religious with my sleep schedule.
During the experiment, I did not change my bedtime or my wake-up time. There was no significant changes in sleep duration or quality. I also did not change any sleep-related supplements.
As monitored by Oura Ring, sleep time was between 7.5 - 8 hours per day with a sleep score of 80 on average.
The below is a gallery of images you can click through (4 in total) showing the sleep score and total sleep from early and late in the self-experiment.
Controlling Exercise
As set out in the opening post for this self-experiment, I maintained a consistent exercise load to within 10% on average (in a given month) as measured by my Garmin smartwatch and heart-rate monitor.
No significant changes were made to total time exercising, exercise intensity or the type of exercise I was completing.
I kept up my routine of 4 weeks of triathlon training with a one week de-load. Average load over the period was unchanged at around ~750-800.
Controlling Stress
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This aspect of the self-experiment was more interesting! I’d originally set out to complete this experiment over 6 months with two GlycanAge tests. However I cut it off at 3 months. Why?
Australia went into a sudden COVID lockdown, upending my life routine and introducing significant additional stress (homeschooling in and of itself would confound the results, haha!).
I simply could not continue the self-experiment for the additional 3 months and maintain good control over the experiment.
Thankfully, I was able to complete the 3 month self-experiment with no significant lifestyle or stress related changes. So this was well-controlled overall.
Conclusion: Eating a diversity of plants significantly improved my GlycanAge
To design this self-experiment, I used Dr Jenna Macciochi’s suggestion to eat 30+ plants per week to boost the immune system.
Immunity: The Science of Staying Well is one of the most up to date, accessible and helpful books out there on building a healthy immune system. Check it out! (Amazon Affiliate link)
We are fortunate to have a pretty clear cut result in this self-experiment.
It was well-controlled and occurred over a short-time frame, with very limited opportunity for external factors to confuse the result.
Moreover, the magnitude of the change in GlycanAge was significant. A 6 year improvement is well outside the measurement error.
Had my GlycanAge improved by only 1-2 years, we would not be able to make such a strong conclusion.
In addition to the size of the change in GlycanAge, there was significant improvement in all three of the glycan indices, where I improved by ~10% in age group relative terms.
This firmly suggests hypothesis looks to have been ‘proven’, with the expressly limited scope of this being an ‘n of one’’ dataset.
Conclusion: Eating more plants improves GlycanAge (for me, and maybe you as well!)
Practically, what does this mean?
For one, I know that I should most definitely keep eating 30+ plants/week! I now consider this part of my longevity strategy.
This is in addition to other tactics like supplementing with NMN, which I also determined to improve my biological age through a seperate self-experiment.
This is precisely how we should use these types of tests. In an intentional and controlled way to test a change and see if it helps you in your longevity journey.
While the ‘conclusion’ is only applicable to myself, this design of this self-experiment provides the opportunity for other wellness and longevity enthusiasts (that’s you!) to use this approach to improve their biological age.
However, if you do not already have healthy diet, exercise, sleep or stress habits - start with those first! Don’t forget that losing weight is the surest path to reducing inflammation and improving your GlycanAge (we asked Gordan!)
If you plan to give it a try, be sure to reach out on Twitter or Instagram and let me know!
You can check out GlycanAge test kits here, and don’t forget to use the code “LONGEVITYBLOG” to save 15% on your order!
Follow me on Twitter for the latest #Longevity news!
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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.
Self-experimenting with GlycanAge - Before and After Diet Changes
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Glycan Age Test review & Self-experiment
As we’ve learnt over the past few posts, glycans are incredible molecules with many important roles in the body.
Perhaps the most important of which is providing information to our immune system about what foreign molecules (i.e. diet, dust particles, bacteria, etc!) are friend and which are foe.
My GlycanAge biological age test kit - just a few drops of blood, drop it in the envelope & it’s ready to go!
As such, they strongly regulate inflammation in to the body, and as we’ve learnt - they are impressively capable of predicting age-related disease onset.
Also, their ‘youthfulness’ can maintained by paying attention to certain lifestyle factors - chiefly diet, exercise, stress and sleep - monitoring them can help us track how we’re doing as we biohack our way to long & healthy lives.
In this post we’ll cover:
The role of glycans in immunity
How glycans are involved in the digestive system
How to use diet to improve GlycanAge
Why food is information for the immune system
Setting up a self-experiment for improving GlycanAge
Plus - snippets from our interview with world expert on glycans - Professor Gordan Lauc
Glycans Regulate Immunity
It is the role of glycans in immunity and disease related processes which makes them so important with respect to the aging process.
Such is their potential impact, that any personalised longevity strategy should likely include an effort to maintain youthful glycan characteristics.
A tumour cell being tagged with 'bad guy’ glycans (represented by the squares, circles, diamonds on cell membrane). Image credit: Gly-tech
“Youthful” in this context essentially means ‘anti-inflammatory’, meaning:
the immune system is not overactive
chronic inflammation is not present (or in advanced age, well managed)
the ravages of inflammaging (the negative feedback cycle of inflammation creating more damage & inflammation) are avoided
How Glycans Impact the Immune System
As we learned in our exclusive interview with world expert in all things glycans, Professor Gordan Lauc, glycans keep track of foreign materials in the body, tagging them as ‘friend’ or ‘enemy’ so that our antibodies know whether to activate inflammation (attack) or suppress inflammation (don’t attack).
“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”
Glycans, Immunity and Digestion
A major role of this immune surveillance process is centred on digestion. This is because the process of taking what we eat, and turning it into our own cells or energy requires active decision making on what should be allowed into the bloodstream.
Ultimately, food is “a foreign object” (using Prof. Lauc’s words above) that has entered the body.
This is clearly done for the purposes of providing fuel and supplying important nutrients, such as vitamins and minerals. However, much more than simple nutrition comes along for the ride.
This includes a host of ‘commensal’ (friendly) bacteria, and sometimes, bad ones, along with the occasional plant compounds that may stress the body (such as glycoalkaloids in the ‘nightshade’ family of veggies).
Our immune system has an important role to play in screening which of these compounds should be permitted to pass through the wall of the small intestine and into the blood stream.
We’ll revisit this in detail later in the post!
Using Diet to Self-Experiment with GlycanAge
I (Nick here! Founder at Longevity Blog) am currently experimenting with improving my GlycanAge through a change in my diet, and in this post, I’ll explain what changes I am making, why and how to make this self-experiment an effective one.
Changing diet to improve my GlycanAge - can it be done? Certainly - the question is - for relatively health people, how?
This self-experiment will explore a hypothesis related to increasing the diversity of plants in my diet and potential improvement in my GlycanAge.
However, before we get into the specifics on how this experiment will work, let’s introduce some important background knowledge to support the approach.
Improving GlycanAge with Diet
Improving GlycanAge through changes in your diet can be either quite easy or mysteriously challenging.
If you’re someone who needs to lose some weight - you’re in luck. You can very likely improve you GlycanAge by simply losing weight. Look no further than our interview with Professor Lauc for the reasons why:
“Longevity Blog: 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 _____ ?
Gordan Lauc: One good example is weight loss. Losing extra weight helps the vast majority of people, because obesity is a big driver of inflammation.”
However, if you’re already at healthy weight, how to use your diet to improve GlycanAge is not immediately obvious. In fact, clinical research with GlycanAge and diet has shown this to be quite challenging (see below tweet & follow me on Twitter for more!).
1000 people were divided into groups eating very different diets
— Nick Engerer (@nickengerer) July 16, 2021
The outcome? It was impossible to predict which diet was best for whom
However, by monitoring glycans, that became possible. Their role in inflammation signalling can reveal - what diet works best for you? pic.twitter.com/D7AyNlzVfp
Improving GlycanAge with Diet by Eating More Plants
Despite this challenge, I believer I have developed a solid hypothesis for testing how people at a healthy weight may be able to reliably improve their GlycanAge.
Through some serious homework, I also believe that this proposed change in diet that would also have relevance to other self-experimenters, and it could be replicated reliably.
This approach will leverage the sub-process of our immune system screening food particles and non-human organisms (i.e. bacteria) as they are processed in the duodenum (small intestine).
This critical step occurs before entering food materials and/or friendly bacteria are permitted to enter the bloodstream and intimately involves - you guessed it, glycans!
Food as Information for the Immune System
To continue down this line of reasoning, you need to adapt your thinking of the small intestine. Stop thinking of it as ‘inside’ your body, and start thinking of it as ‘outside’.
It is within the small intestine where a critical decisions is made - namely, what foreign materials from the diet are permitted to enter the blood stream.
Pictured: Intestinal villae, lines with intestinal epithelial cells (IECs) along with several other functional cells include macrophages (immune surveillance cells). Image Credit: Nature Reviews: Immunology
The small intestine is lined with “intestinal epithelial cells” or IECs for short. IECs are a single layer of cells with two key functions:
1) be a barrier to anything harmful - toxins, bad bacteria, viruses or antigens
2) act as a filter, whereby nutrients, electrolytes, water and beneficial bacteria are allowed into the bloodstream.
In this secondary function of ‘filtering’ where a detailed and highly important involvement of the immune surveillance system takes place.
The details are vastly complicated, but we can afford a useful simplification here.
Assuming you have tight junctions between the epithelial cells of the small intestine, only the foreign material ‘accepted’ by your immune system is permitted to pass through.
Anything else - and your immune system signals ‘attack’ - producing inflammatory signals.
IGG glycolisation (that’s science talk for how glycans are being used within the body - read more about this in the interview with Prof. Gordan Lauc) plays a critical roles in this screening process, and the ‘tagging’ of foreign material as friend or foe is at its peak level of activity at this epithelial junction.
Critically - this highly complex process includes many trillions of bacteria, which participate in the breakdown and processing of food materials by the body.
These so called ‘commensal’ bacteria are actually actively recruited and ‘pulled through’ the epithelial junctions by the immune system.
The commensal bacteria are pivotal to your broader bodily health, with your overall wellbeing depending on a vibrant and diverse population of these friendly bacteria in the gut.
Food as Information
Local organic root vegetables from our weekly farmers market. Covered in healthy soil based commensal bacteria - just waiting to program your immune system.
The activities of food screening and bacterial populations in the gut are tremendously influential on inflammation in the body.
To better illustrate this, we’ll adopt a basic framework - where our diet is information about our environment.
This is the case because the food we eat, the bacterial populations in that food, as well as ‘antigens’ (‘bad things for us’) effectively ‘program’ our immune system.
In prehistoric times, this information was often life-saving, as it was critical for our bodies to become well adapted to the organisms, toxins and food sources around us in order to survive.
In this way, we evolved for our diet to signal “this is what your environment is like and thus how you should adapt to prepare for it”.
Now consider the modern environment, where food is sterilised and our environment is kept much cleaner than ‘nature’ could ever be. Your immune surveillance system is now cut-off from this critical source of information!
Why does this matter? Well, because in a relatively sterile environment, your body lacks enough exposure to healthy bacteria and the wide variety of food it needs to know when or when not to attack.
What does that mean? A sterile diet effectively means your immune system’s default mode is ‘attack’. The immune system, out of interest in self-preservation, will work to eliminate a foreign material it is not comfortable with (used to seeing).
Add it all up and you get - you guessed, more inflammation.
Eating a Diversity of Plants Programs Immunity
In viewing food and organisms from the environment as information, we can begin to build up our glycan self-experiment in the following way.
If your body is not provided a diverse amount of information about the environment through a diversity of food and organisms through the diet, it will tend to react with ‘attack’ more often.
Through our framework: less information = more inflammation.
On the flip side the pathway to reconciling the overactive immune system is through providing ample information about the environment through the diet.
Dr Jenna Macciochi’s Immunity: The Science of Staying Well is one of the most up to date, accessible and helpful books out there on building a healthy immune system. (Amazon Affiliate link)
This will then support the immune system with a more comprehensive view of what foreign materials are ‘friendly’ and which are not.
This conceptual framework is precisely what Dr Jenna Macciochi lays out in her book Immunity: Science of Staying Well.
One of the key recommendations from this exceptionally insightful book is to eat a diversity of plants regularly, preferably local and organic ones.
The result will be a stronger immune system, which Dr Macciochi argues, is one of the only *real* ways to “boost your immunity”.
In her book, immunity expert Dr Macciochi says there is a valuable ‘rule of thumb’ for improving your immune system with diet.
What’s the rule? We’re glad you asked..
“A good rule of thumb for the biggest impact on health is to aim for over 30 different plants per week.
Whereas the opposite is also true. Eating 10 or few has a potentially damaging effect on the microbiota”
Why is this the case? It’s all about diversity of information about the environment.
And that information is programmed in the body via your glycans.
GlycanAge Self-experiment: A Diet with Diversity of Plants
My GlycanAge as of April 2021 is already ‘favourable’. But that’s not good enough for a longevity focussed biohacker now is it?
How low can we go?!
Coming full circle, this logic leads naturally to the experimental hypothesis:
“By programming the immune system with a diversity of plant information (local & organic where possible), chronic inflammation will be reduced as the immune system learns more about what is friend and what is foe, leading to an improvement in the Glycan Age”
The is precisely the hypothesis that this self-experiment will evaluate. So let’s get down to it!
My GlycanAge was first measured in April 2021.
My GlycanAge is 30, whereas my chronological age is 35.
According to Prof. Gordan Lauc, this is a great result.
“Longevity Blog: What is a “good” GlycanAge result Gordan?
Gordan Lauc: 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.””
Self-experiment: Starting Conditions & Control
This result does make sense. In the 6 months leading up to this test, I maintained optimal levels of physical activity (training for sprint triathlons), a healthy balanced diet (eating small meals across the day, mostly vegetarian but with animal protein 3-5x/week), sleeping fairly well (Oura ring sleep scores at 75-85 on average) and well managed stress levels.
So in each of the four levy lifestyle factors (diet, exercise, sleep, stress) for my GlycanAge, things were in tip-top shape.
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In this self-experiment, beginning from 1 May, I will eat 30+ plants per week.
Where possible, this will be from local and organic sources (of which we have plenty in the Byron Bay Area!).
Experimental Control
As discussed in my previous foray into self-experimentation with the NAD precursor NMN, it is challenging, but not impossible, to perform a well controlled self-experiment.
We approach this by keeping lifestyle factors as constant as we can, not changing any other key variables, and running the self-experiment for as short a time as possible.
For the GlycanAge self-experiment I will:
maintain a consistent exercise load to within 10% on average (as measured by my Garmin smartwatch and heart-rate monitor)
keep my same sleep schedule (7-8 hours a night)
not make any large lifestyle changes that might negatively impact my stress
not make any other changes to my diet (we’ll have to keep in mind that my diet will also have a reduction in non plant foods - to make room for all of the plants!)
Experimental Test Period
The experiment, according to advice from Prof Lauc will be run for a minimum of 3 months and maximum of 6 months.
This means I will re-test date on 1 August and again on 1 November.
I asked @GordanLauc - how often should we test @GlycanAge?
— Nick Engerer (@nickengerer) July 20, 2021
⁰⁰The half life of IGG glycolisation is ~3 weeks. 1 month would be the shortest period for re-testing
Lifestyle change effects take a bit longer. Modify diet, sleep, stress or exercise?
Recheck every 3 to 6 months pic.twitter.com/hjuVEdWIBo
Other Relevant Items
To keep track of my plant intake, and ensure that eat enough plants, I am keeping a weekly record of all of the plants that I eat.
I keep this pretty simple, recording them in the iOS notes app - presumably you could do this just about anyway that you please.
There is of course an important question - what is a ‘plant’? What counts as 1x plant?
I will only be counting whole food plant sources which equate to at least one serving of that food.
So for example, I would not count ‘bread’ to be a plant, although it comes from wheat flour at it is quite refined/processed (not a whole food). I would however count rolled oats as a 1x plant (limited processing, effectively a whole food item).
Follow our Founder Nick on Twitter for the latest #Longevity news!
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RT @rebeccavziegler: The cryonics payoff matrix. Choose wisely my friends. https://t.co/l1rzsmOC2w
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My rate of aging: 0.79 It’s the new street cred What you got? https://t.co/aHzWHAfCnD https://t.co/L3rZC4QFN2
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It’s official - I’m co-producing and hosting a new #longevity docuseries, and will begin shooting in a few months… https://t.co/wLGqRrBfbp
-
“The #longevity segment opened my eyes to the groundbreaking advances in biotechnology, health, and wellness. The i… https://t.co/F8YB7PAeMW
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I’m completely mindblown by what AI has done over the past 3-6 months, and it continues to accelerate… https://t.co/hh0JslucRg
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Longevity legends take on many shapes and sizes https://t.co/X9vGa7gvOe
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RT @BradStanfieldMD: Avoid These Popular Supplements (shout out to Professor Matt Kaeberlein @mkaeberlein & Professor Brian Kennedy… https://t.co/cy9CXldgUS
-
Who are influential persons in #longevity who are of Asian, African American or other “minority” group in the US?
Nick also posts related #Longevity content to Instagram as well, follow him at @nickengerer
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!
GlycanAge Discount Code!
As a part of our mission, we are working to make your longevity budget stretch further!
Through our collaboration with GlycanAge, we have a 15% off coupon code, which you can use on their biological age test kits.
Use the code “longevityblog” to save 15% on GlycanAge
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.
Biological Age Testing with Glycans - Glycan Age
Should you try a Glycan Age Test?
The GlycanAge test kits - a clean, elegant design with fascinating technology under the hood.
This trend is in its early stages, but is set to continue, as gathering detailed information about your body to assess how quickly it is ageing hits the mainstream.
Today, we are introducing you to a new way to assess your biological age.
Whereas previous methods we have reviewed use age-related blood markers or your epigenome for this assessment - today’s technology from GlycanAge uses your glycans.
What are Glycans? Glycans and Biological Age
To start things off, we should probably address your first likely question - what the heck are glycans?
Clearly we need to understand this a bit first, before we can understand how they can be used as a biological age measurement.
Glycans is not a term that most people are familiar with, but they actually refer to a fairly simple concept.
First, we start with monosaccharides, which include more commonly known ‘sugars’ including fructose, glucose, and galactose.
Most of us are familiar with these monosaccharides - they are the simple carbohydrates common in our diet. More broadly, they can be thought of as the ‘fuel’ for our cells, as well as the energy source for most biological organisms!
use the code “LONGEVITYBLOG” at checkout to save 15% on GlycanAge tests
Glucose Molecule (Monosaccharide)
Fructose (Another Monosaccharide)
Combining Monosaccharides to Create Glycans
In practice, monosaccharides can actually be linked together in a very wide variety of long chain-like formations. This how you create a glycan.
A very well known glycan (also known as a polysaccharide) is cellulose, take a look at how it is built out of the monosaccharides above, just in a much more complex arrangement.
Cellulose - a combination of glucose molecules to form a glycan
Glycans and information
Glycans are influential in many processes occurring within your body. One way to think of their involvement is carriers of information.
As complex arrangements, there are many unique arrangements of glycans in the body which often represent very important signals regarding your health and wellbeing.
A healthy cell, with healthy glycans at the cellular membrane (the multi-coloured squares, circles and lines). Credit: Gly-tech
The valuable ‘signal’ that these complex sugar structures can offer has resulted in the field of ‘glycoscience’, which studies wealth of information glycans have to offer.
This information includes critical details about your overall wellbeing, with the presence (or absence) of certain glycans can be indicative of many conditions in the body, including many diseases, as well as - you guessed it - the processes behind ageing itself.
Glycans, Inflammation and Ageing
An unhealthy cell, with unhealthy glycans at the cellular membrane. Credit: Gly-tech
Glycans are intimately involved with your immune system, where they are used to ‘tag’ invading pathogens, signalling the immune system to attack and remove them.
Furthermore, the wrong glycans in the wrong place can generate an immune response, which then drives inflammation.
If you’ve learned about the basics of aging, and many of you have, you’ll be quite aware of the importance of tracking and managing inflammation to stay healthy for as long as possible.
The link between inflammation and ageing is known as ‘inflammaging’.
Dive deeper? Read more about inflammaging straight from the source in this very important 2014 paper which established the concept.
High level overview: Inflammaging is the process whereby increasing levels of inflammation add continual age-related stress and damage to the body, including more inflammation - and thus a feedback cycle develops making you age even faster.
Sounds like a great thing to keep in-check, no?
The links between inflammation, aging, and glycans are what make glycans great choice for monitoring your biological age.
GlycanAge as a Biological Age test
While glycoscience still has much to learn about glycans and their role in aging, metabolism, disease and immune function, there are many decades of research and enough large datasets available to support the creation of a biological clock based on glycans.
We’ll be covering the specifics on how this works in upcoming posts, but the key takeaway is: tracking the characteristics of the glycans in your body can provide an accurate and valuable assessment of your biological age.
And in the case of GlycanAge, your biological age will be primarily influenced by four lifestyle factors:
Stress levels
Exercise load (both too little and too much)
Dietary choices (including food allergies)
Sleep (what’s the right amount for you?)
Each of these factors are known to be very influential in how you are ageing.
As such, you can use a GlycanAge test to create a baseline, before making controlled changes/improvements in these factors, and then re-testing to see if they worked (i.e. did you reduce your biological age?).
This is central to what Longevity Blog is all about - self-experimenting and customising your own longevity strategy to make the best gains in your healthspan.
Given the nature of these lifestyle factors (stress, diet, exercise), self experimenting with GlycanAge is a very accessible way to start working to improve your own biological age.
Regularly testing GlycanAge can therefore be used to monitor and improve your health over time, with each of those small changes adding up to positively impact your longevity significantly over time.
GlycanAge and Its Mission
Don’t miss it!
We’ll be interviewing glycan expert Gordon Lauc on how you can used GlycanAge to improve your own health & longevity. Subscribe to get notified when we do!
The concept of using glycans to track and positively impact your healthspan has only been made possible through the vision and ambition of GlycanAge’s CEO and Founder Nikolina Lauc
Founded in 2016, the company is built upon the foundational work carried out by expert in all things glycans Professor (and Nikolina’s father) Gordan Lauc.
But don’t take it from us - hear it straight from Nikolina herself:
GlycanAge Founder and CEO Nikolina Lauc
Describe your motivations for founding GlycanAge - what opportunity did you see?
Nikolina Lauc (NL): GlycanAge originally came out of pure scientific curiosity.
My father is a glycobiologist who's worked in the glycan research field for 30+ years, they saw that glycans change with age and were curious as to how and why they change, as well as what we can do to influence it.
Hence the term GlycanAge, actually “GlycanBioAge” originally, was coined.
Glycans are one of the key regulators of our immune system, they contribute to ageing through a process called inflammageing.
Inflammation is a key driver of almost all chronic conditions and glycans are known to change before onset of symptoms and even a decade before onset of disease, giving us an opportunity to do true prevention and extend one's healthspan.
“Glycans are known to change before onset of symptoms and even a decade before onset of disease”
How would you describe GlycanAge’s mission - what drives your team? What have you set out to achieve?
NL: We want to keep you and your loved ones around for longer through precision health.
Our mission is to bring glycoscience into the hands of both clinicians and consumers to inform, guide and preserve your future health.
Glycans have a large influence on your unique biology, they play an intermediary role between your genetic potential and end phenotype, their true value lies in uncovering which intervention or lifestyle works for you particularly as an individual.
How has regularly testing your own GlycanAge improved your wellness?
“Glycans true value lies in uncovering which intervention or lifestyle works for you particularly as an individual.”
NL: Although my GlycanAge has always been favourable, regular testing helps me measure the damage (for example - COVID lockdowns and weight gain), and get back on track through sustainable change.
Beyond me, I've probably tested the majority of my extended family!
Coming Up:
(1) An interview with GLYCAN expert Gordon Lauc (read that here!)
(2) How our Founder Nick is using GlycanAge to run his own self-experiment (read it here)
Follow our Founder Nick on Twitter for the latest #Longevity news!
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RT @rebeccavziegler: The cryonics payoff matrix. Choose wisely my friends. https://t.co/l1rzsmOC2w
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My rate of aging: 0.79 It’s the new street cred What you got? https://t.co/aHzWHAfCnD https://t.co/L3rZC4QFN2
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It’s official - I’m co-producing and hosting a new #longevity docuseries, and will begin shooting in a few months… https://t.co/wLGqRrBfbp
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I’m completely mindblown by what AI has done over the past 3-6 months, and it continues to accelerate… https://t.co/hh0JslucRg
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Longevity legends take on many shapes and sizes https://t.co/X9vGa7gvOe
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RT @BradStanfieldMD: Avoid These Popular Supplements (shout out to Professor Matt Kaeberlein @mkaeberlein & Professor Brian Kennedy… https://t.co/cy9CXldgUS
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Who are influential persons in #longevity who are of Asian, African American or other “minority” group in the US?
Nick also posts related #Longevity content to Instagram as well, follow him at @nickengerer
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 Nicotinamide Mononucleotide Before and After
NMN Before and After with Biological Age
In mid 2020, I set out on a self-experiment with NMN. The purpose of this experiment was three-fold
First - my primary intention was to lay out some suggestions for how you could structure your own self-experiments, and not just for NMN
Second - I of course was quite curious what my own results would be, and wanted to have a well-controlled self-experiment to answer the question: should I continue to invest in NMN as part of my longevity supplement stack?
Third - to raise awareness of NMN, biological age testing and encourage more of you to join in on being a biohacker!
Designing a self-experiment with NMN in mid 2020 was a unique challenge, as at the time, there was no direct way to test intracellular NAD levels.
That has however changed, and in upcoming posts, I am going to show you how to test your NAD levels directly. If that sounds interesting, be sure to subscribe below!
Takeaway: Over 6 months, a combination of 500mg NMN, 500mg TMG and 500mg resveratrol improved my biological age by 3.5 years. Read on to learn more!
Use the code ‘longevityblog’ to save 10%.
Looking for an NMN supplier? I recommend DoNotAge, who:
offer a third party tested product
have a bulk supply option (100g)
offer further savings when you subscribe to regular shipments
plus I can get you a discount: Use the code ‘longevityblog’ to save 10%!
Self-Experimenting With NMN
It is not easy to run a self-experiment. To review, all self-experiments are:
Difficult to control
Often hard to measure directly
Prone to bias and placebo effect
Even when well-controlled, don’t necessarily provide clear insights
Let’s take a minute to address each of these, how this particular self-experiment addressed each over the course of the 6-months of NMN supplementation.
Control
Over the course of my 6-month experiment, I made several efforts to control the experiment:
My exercise ‘Load’ as per my Garmin Fenix 6 Pro, which I use to track all of my workouts. At top, near the start, at bottom, near the end of the 6 month period.
I did not change my exercise load or volume
I did not change my diet
I did not start taking any other supplements
I did not make any other major lifestyle changes
It is of course not possible to completely control your life! However this does not mean you should not try.
Of these items, I would suggest that consistency in diet and supplementation are of paramount importance.
You can find many “NMN before and after” testimonials on YouTube, for example, but each of these has many problems with control.
The most common issue is making too many changes, mostly around supplementation protocol, during the ‘before’ and ‘after’ period.
Your chief goal here is to decide: is taking NMN worth my hard earned cash?
You can’t make that call if you’re also introducing many other longevity supplements at the same time! You’d be surprised how often this is the case! Be patient and be consistent.
Measurement
In the absence of a direct NAD test, the decided measurements before & after were set according to the 2x clinical NMN trials which were ongoing at the time, as well as adding biological age:
Lipid profile
Blood pressure
Biological age
Epigenetic age (Saliva Test via Chronomics)
Phenotypic age (Blood Test)
Bias & Placebo
I put serious thought into how to conduct a double-blind experiment, but ultimately elected not to.
Given the objective measurements we could draw from the above, and the ‘n of one’ experimental design, this was not practical to implement.
It also reduced the likelihood that everyday folks like yourself would be able to repeat the experiment effectively.
In the effort to minimise placebo effect, I made it my mindful intention to not overhype my personal attitude toward the experiment.
To be quite honest - I adopted quite a sceptical attitude.
Personally, I was unconvinced that NMN would make much of a difference in my day-to-day experience, as there was relatively little science in human subjects & most of these ‘hot trends’ turn out to be over-hyped!
NMN
NMN Self-experimentation Protocol
The supplement protocol for this self-experiment was designed to match the widely used combination of NMN, Resveratrol and TMG:
NMN at 250mg/day (first two months), 500mg (following four months)
For risk management, 1:1 dosage of Tri-Methyl Glycine (TMG)
Resveratrol at 500mg/day, taken with a high fat meal
Note: this was not a change for me, I’d been taking it for 2+ years, and therefore did not interfere with the need for supplemental control
NMN Before & After: Our Hypothesis
This experiment was undertaken to test the following hypothesis (all self-experiments should have one!):
NMN supplementation will boost intracellular NAD+ levels
Boosting NAD+ levels with NMN will measurably improve select characteristics of youthfulness
Combining boosted NAD+ with a sirtuin activator (resveratrol) will enhance DNA repair
Combined, these effects are hypothesised to be likely to:
change blood lipid profile (as per clinical trial designs)
change blood pressure (as per clinical trial designs)
slow or reverse biological age (Longevity Blog hypothesis)
NMN Before & After: Results
The self-experiment was run from 1 August 2020 for 6 months until 31 January 2021.
What follows are the results, including both hard data points and anecdotal observations.
Blood Lipid Profile:
Blood lipids refer to the commonly assessed HDL, LDL and Total Cholesterol measurements. These are also joined by Triglycerides to form the ‘Blood Lipid Panel’ of tests.
As you can see in the provided image, there was no significant change in any of these parameters over the course of my NMN self-experiment.
Blood Pressure
Blood pressure measurements at the start of the experiment were ~125/85.
At the end of the experiment, 126/84.
There was no significant change in blood pressure from the NMN self-experiment.
Biological Age: Phenotypic Age
Phenotypic age is calculated using 9 blood based biomarkers, to calculate a biological age.
This is based on work led by Yale researcher and longevity thought-leader Dr. Morgan Levine (whom we hope to interview on the blog in the future!).
We’ve previously reviewed this test, including providing information on how you can use it yourself here (its free!).
Blood markers in this test include:
White Blood Cell Count (WBC)
Red Cell Distribution Width (RDW)
Mean Corpuscular Volume (MCV)
Fasting Blood Glucose
Lymphocyte %
Creatinine
Albumin
Alkaline Phosphatase (ALP)
C-reactive protein (CRP)
If you’d like to learn more about any of these blood markers, checkout Lab Tests Online.
Pictured: My Phenotypic Age (Biological Age measure #1) over time.
At the start of the self-experiment, my Phenotypic Age was 28 (Chronological Age 34).
At the end of the self-experiment, my Phenotypic Age was 25 (Chronological Age 35).
Given that 6 months passed, this equates to a total change of -3.5 years of Biological Age.
Did I reverse my biological age with NMN?
Now - the key question is, was this change significant? Was it due to the NMN based protocol?
This comes back around to one of my initial opening points about self-experiments: “Even when well-controlled, they don’t necessarily provide clear insights”
For our analysis, we should extrapolate from the baseline measurements a bit further.
Over the preceding 3 years, my Phenotypic Age was an average of 25.7 years old. It was as high as 28 and as low as 23.
More importantly, we need to consider the difference between biological age and chronological age.
My average difference between biological age and chronological age over the preceding 3 years was -7.7 years. This was as high a -10 years and as low as -5 years.
At the start of the NMN self-experiment, this difference was -7 years (below the average), whereas at the end, it was -10 years (at the previous extreme).
There is a degree of subjective interpretation which must occur here, as the data volume does not lend itself to statistical analysis.
Based on the data and trends, there is sufficient evidence to suggest that this NMN based protocol reversed my biological age.
It is however is not conclusive evidence, and as a scientist, I choose to approach that statement conservatively.
There is a bit more to explore however, to let’s continue.
Biological Age: Epigenetic Age
This one was a real bummer. My follow-up test with Chronomics failed their quality control step, meaning the biological age result was not valid.
This was a crushing blow, as it was the chief data point, in my opinion.
However, I have re-tested it, but it was not in-line within the 6-month period self-experimentation period.
Due to my choice to begin another 6-month self-experiment immediately following this one, the next biological age result will not be valid for this experiment.
I’ve since dramatically increased my exercise routine (I’m now training for triathlons), made major dietary changes and increased my NMN supplementation to 1000mg/day in a separate 6-month self-experiment aimed a direct feedback from Chronomics on how to reverse my biological age.
I will update this post with those results, when they are returned, however they will not be well-controlled for NMN experimental purposes.
I know - major bummer! 😔
Such is self-experimenting life!
NMN Before and After: Anecdotal Observations
SF-36 Questionnaire
My results from the SF-36 questionnaire before & after did show a slight change in a few key areas.
While I did not experience any changes in general health, physical health problems or limitation of activities, I did have interesting results in the energy & emotions section.
Excerpt from my SF-36 questionnaire, before and after the NMN self-experiment.
At the start of the self-experiment, I think I was feeling many of the things that folks in their mid-30s start to feel. Notably less energy than in their 20s, less upbeat and more likely to feel worn out at the end of a long day.
Over the course of the self-experiment, this changed in notable ways, in a sustained way that continues to today.
You can see for yourself the meaningful parts of the questionnaire that changed for me in the following image.
I have to add - it is completely possible that these results are placebo based. I was taking NMN, most folks who supplement with NMN boast ‘increased energy levels’.
But of course, since NMN is hypothesised to impact intracellular energy, this is what we expect to happen.
When it comes to ‘energy levels’, NMN is a prime placebo influence candidate.
Nicotinamide Mononucleotide Before and After Conclusions
To summarise, I was able to run a well-controlled self-experiment with NMN supplementation at 500mg/day.
I recorded before and after blood tests, blood pressure and detailed subjective experience related data.
Initial results do indicate improvement in my Biological Age (as per the Phenotypic Age) by approximately 3.5 years.
Subjective data (qualitative data) support this quantitative data, and therefore the conclusion is: NMN left me both feeling younger and perhaps biologically younger.
However, this cannot be placebo controlled, and warrants further testing. In particular, direct testing of NAD levels is now available, and that is what I will be testing next!
Also, we have not been able to test the much more robust and accurate epigenetic age via Chronomics, which was unable to be measured. Ultimately, this was the most powerful data point, and though disappointing - we will revisit it.
Coming soon, I will review the results from testing intracellular NAD levels directly, before and after 1000mg of NMN.
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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.
Choosing an NMN Supplier for Self-Experimentation
What is the Best NMN Supplement?
Who should you choose for your NMN supplement?
Fast-take: I recommend DoNotAge, who offer a third party tested pure product, have a bulk supply option (100g) with further savings when you subscribe to regular shipments. Use the code ‘longevityblog’ to save a further 10%!
Want the details and the ‘why’ I make this recommendation? Do read on!
Today on Longevity Blog, I wrap up my three part series on self-experimenting with Nicotinamide Mononucleotide. Complete with NMN before and after testing.
As discussed in the first post of the series on NMN risk management, there are three key questions that Longevity Blog will engage with on the topic of NMN. These are:
What NMN supplement should I use?
In this third post of the three-part series, we’re going to zoom right in on the question - how do I choose a high quality NMN supplier?
Choosing the best NMN supplement: Potential Pitfalls
NMN is a supplement, meaning its production and distribution are largely unregulated. As such, this potentially exposes the self-experimenter to several potential pitfalls when purchasing.
The most important of which are:
Imposters (i.e. not actually NMN)
Contaminants (e.g. heavy metals)
Impurities (e.g. fillers, extras)
Unnecessarily high cost per dose (e.g. low potency)
Naturally this raises the question - How can we avoid these potential disruptors to our self-experimentation?
For those currently searching for their own NMN supplier, I personally understand where you are coming from.
First up - you are aiming to purchase a product with confidence in knowing it is NMN, but fake supplements are common and are lurking amongst in the available NMN suppliers on the web right now.
Even if you can become confident the product in question is NMN (not an imposter), you still must consider the risk of contaminants such as heavy metals showing up in your supply.
Furthermore, we don’t want to waste our money on a product that has low potency and/or uses fillers to push more product (impurities).
And then there is cost. Once satisfied on the above three - imposters, contaminants, impurities - we still need an NMN supply that fits our budget. This is complicated by varying levels of potency across the options:
what is a ‘dose’?
how much NMN per dose?
how many doses per container?
shipping costs?
The above long list of factors can make selecting an NMN supplier quite daunting, and perhaps overwhelming!
No one individual can take on the challenge of sorting through these points on their own. Thankfully, the NMN self-experimentation community is working together on this one…
NMN Supplement Review Useful Sources
One of my favourite aspects of the self-experimentation community, is the collective spirit of sharing knowledge and helping each other navigate the pitfalls of sourcing supplements.
Despite its relative novelty, NMN suppliers have been usefully reviewed in several formats - the most valuable of which, at this stage, are two YouTube videos.
In the first, we find that once again, my mate Dr. Brad Stanfield continues to be one of the top sources of information on NMN.
In his videos, he reviews several brands - and parallels my above selection criteria - analysing imposters, impurities, contaminants and cost per dose.
Dr. Stanfield’s endeavour to find 3rd party testing data reveals a key resource in our journey to select our NMN supplier.
The second YouTube video is from Vince and his channel “My NMN Experiment”.
Vince has several relevant videos for the NMN self-experimenter on the topic of NMN sourcing, self-experimentation and review of available third party testing.
Of particular use is his video on ‘Testing Heavy Metals” which you can view below:
Choosing the Best NMN Supplier
Use the code ‘longevityblog’ to save 10% on any order with DoNotAge
Amongst the growing number of choices for supplying NMN, is UK based company DoNotAge.
I recently became a strategic advisor to this company, owing to our shared interest in making longevity supplements like NMN widely available.
Simply put, if NMN can deliver even a fraction of the longevity benefits to humans that are observed in mice, then I firmly believe in the democratisation of access to the molecule.
By democratisation, I mean - making it widely available in both supply and cost. Quality is of course pre-requisite.
Before we move on, it is important to disclose that I stand to benefit from the sales of NMN by DoNotAge due to my advisory role.
However, this monetary benefit is modest and frankly, is not part of what motivates me to self-experiment with NMN, nor to recommend the company to you personally.
Instead, what my position as an advisor has allowed me to do is more clearly understand the NMN global supply chain and access certain confidential information about its production, proprietary competitor testing, distribution and profit margin.
Many NMN options are low quality
Through the clarity this position has provided me, I have a heightened level of concern on the practices of many of the other NMN suppliers.
The issues I am now privy to are numerous and commonplace. I am aware of products sold on Amazon, claiming to be NMN, which contain nicotinamide instead (imposters).
Suppliers who claim to be ‘manufactured in the USA’, source their products from China (lack of integrity) and package it in the United States in order to ‘cheat’ their way to this label.
Others have degradation of the product due to poor packaging and storage practices (potency), while many others provide no third party certification regarding heavy metals (contaminants).
Moreover, many sell NMN at low potency, including doses at 50 - 150mg, which are well below even the conservative doses being used in early clinical trials.
DoNotAge is a High Quality Supplier of NMN
In addition to the “insider scoop” on the NMN supply landscape, my advisory position has also provided me with a high degree of confidence on DoNotAge’s Pure NMN product.
I know with certainty it is NMN (not an imposter), is appropriately free of contaminants or impurities, and it is amongst the highest potency options available on the market (500g NMN per capsule).
This combination of factors given me the confidence to personally consume the DoNotAge product, using it in my current NMN self-experiment, selecting it from the ‘Wild West’ of NMN suppliers.
Despite the potential conflict of interest I hold in monetarily benefiting from the sales of this product, it is my hope that this vote of confidence may contribute to your own decision making process.
Simply put - in my longevity journey, I am very disciplined in choosing the supplements I consume! DoNotAge passes all my checkpoints.
Reviewing NMN for Self-experimentation Protocol:
Use the code ‘longevityblog’ to save 10% on any order with DoNotAge
Zooming out from the details of choosing the best NMN supplier, let’s come back to my NMN self-experiment.
I am presently wrapping up week 4 of the protocol, which will run for a total of 6 months.
The experiment will rely on several different data points, one of which is before & after biological age tests from Chronomics, and will wrap up at the end of February.
Unlike many of the other self-experimenters out there, I am holding constant my daily habits, diet and supplement routine, in the interest of generating the most robust scientific outcome.
When complete, I will finalise the results and protocol, in order to support the self-experimentation community.
The self-experimentation protocol is as follows:
NMN 500mg per day (updated)
TMG 500mg, every day (1:1 ratio to support methylation)
All of which is being supplied by DoNotAge.
You can find the relevant DoNotAge products in each of the above hyperlinks.
Use the discount code ‘longevityblog’ to save 5%!
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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.