How Fast are You Aging? A Biological Age Test for Rate of Ageing with Ryan Smith of Trudiagnostic (Part 2)
How Fast are You Aging?
Are you considering taking a biological age test?
If so, you probably are interested to know - how old am I really?
When investing in a biological age test kit, you’ll want to choose the product which has the best accuracy and precision. What does this mean? We’ll discuss this in detail in today’s interview.
This is of course a tempting data point for those interested in their longevity. But any given biological age test is really only a snapshot in time.
We often argue that the real value in biological age tests is in their ability to test, undertake a longevity self-experiment and re-test to see if your bio age improves. See this example or this example to see what we mean in more detail.
Using test kits in this way mean you really have to purchase at least two biological age tests. Even with the lowest cost kits, this means spending at least $300-$400USD.
However, recent developments in this space mean you can now see your rate of aging in a single test. This arguably saves you on cost twice - as the rate of aging biological age test kit is about half the price of the full test and you only need to purchase one kit.
TrueAGE PACE TEST KIT REVIEW
The capability to directly measure rate of aging has been developed by Longevity Blog partner TruDiagnostic. To our knowledge it is the only biological age test kit with this capability (at the time of writing).
This test (TruAge PACE) analyses short-term changes in epigenetic methylation and is a sort of “speedometer for aging”. Those looking out for their longevity want this speedometer value to be as low as possible!
This kit has very high precision and is very responsive to interventions, whereas most epigenetic test kits giving you a biological age are slow to respond. The TruAge Pace test kit is arguably quite ideal to see which longevity technologies are working for you.
Of course, we’ll be working to prove that hypothesis (be sure to subscribe to monthly updates to hear the answer!)
It is worth noting that the full cost kit from TruDiagnostic - TruAge Complete includes the rate of aging result (as well as extrinsic age, immune age and telomere age + more).
How Does Rate of Aging Testing Work?
To get into the details behind how the TruAge Pace test kit works, we continue our interview series with Ryan Smith the Co-Founder and VP of Business Development at TruDiagnostic.
We recently interviewed Ryan, and in the first part of this series, we had him walk us through the recent developments in biological age test kit technology.
One of the most important take-aways is that you want to be choosing a third generation biological age clock to get the most accurate and precise result. Be sure to review it for more details!
Today, we’re exploring this concept of the rate of aging and looking into Ryan’s view of the longevity technology roadmap - where will biological age test kits go next?
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with TruDiagnostic, we have a negotiated a 12% off coupon code for our readers.
Use the code longevityblog at checkout to save!
This interview was conducted in August 2022 over Zoom and is an audio transcript with edits for clarity, brevity and correctness.
How fast are you aging?
Ryan Smith, Vice President of Business Development at TruDiagnostic is an expert in the latest developments in biological age testing.
Longevity Blog (LB):
TruDiagnostic are also providing an estimate of how fast you are aging. This is unique, and part of the reason this is possible is due to the DunedinPACE algorithm being a third generation clock.
Can you give us a brief history of why the city of Dunedin has become important in building a unique biological age algorithm?
Ryan Smith (RS):
This data comes from a study started in 1972, with a group of right around 1037 New Zealand children all at the age of three. They started this cohort by tracking them all the way across their aging process.
Now we're here, we are in 2022, and these individuals are approximately 50 years of age with 900 or so of those patients providing us information and blood biomarkers showing us how they're aging throughout their life.
Dunedin is located on the South Island of New Zealand. The Dunedin Study has followed the lives of 1037 babies born in 1972/73 since birth.
The study is now in its fifth decade and has produced a considerable amount of data that shapes what we know about the rate at which humans age.
This is a very, very unique cohort that really doesn't have replication anywhere else in the world.
LB: Do we have epigenetic measurements from these folks?
RS: Thankfully, they have saved some of that blood, but unfortunately, we haven't had epigenetic measurements across the entire lifespan.
It would be great if we did, but we have taken a lot of other lab measurements across their lifetime. And those 19 blood related biomarkers are what we have used to train an algorithm to estimate the pace of aging.
Following Individuals Aging over Time = Rate of Aging Algorithm
LB: So there's the connection from the blood based biomarkers to the rate of aging and methylation data. And all gathered longitudinally, again, which is what makes the third generation clock so powerful.
Let’s come back around to DunedinPACE’s (the algorithm behind the TruAge PACE test kit) ability to estimate the rate of aging. Explain how this works.
Source: TruDiagnostic ‘Pace of Aging’ report document.
RS: In order to look at the rate of aging, you have to have some context for the change over time.
What we do is look at all those 19 blood related biomarkers and giving them a composite score. Then looking at how that score changes as these individuals age from the time they were 3 years old to now, we can see what is optimal.
We really get to see what is happening on average to most people as they age chronologically with very little intervention. This gives us a standard to see - what is the average pace of aging?
We can show our customers how they individually compare to that, where we can get an instantaneous point in time measurement of what their aging rate is at this moment.
I think this is very exciting because most other clocks are encompassing the entire body's aging process over the course of a long period of time. But these instantaneous markers are showing how you are aging right at this moment.
This can be very helpful in terms of finding out what lifestyle changes or interventions are working on an individualised basis.
How to Improve Your Biological Age Rate
“We also know TruPace has probably the most accurate or most predictive of all clocks... this rate of aging estimate is responsive instantaneously”
LB: That last part that you just mentioned, in terms of determining what works on an individualised basis, is right at the heart of what we like to do at Longevity Blog.
One thing we find really fascinating about the TruDiagnostic TruAge test kit is this rate of aging algorithm.
We suspect it will actually be more responsive to interventions and helping our readers self-experiment and see how the rate of aging is changing.
The extrinsic age is a pretty sticky number. It's harder to change and takes longer. Do you agree with our thinking? That the rate of aging estimate lends itself better to the everyday longevity enthusiast or biohacker?
RS: I certainly think it does, and I think that we've already talked about some of the reasons why.
One is precision. This clock is extremely precise. That means as you're measuring biological age more frequently, you want an even more precise clock.
We also know it's probably the most accurate or most predictive of all clocks. Ultimately, this (rate of aging estimate) is responsive and responsive instantaneously.
Sometimes it can be very hard to improve or to fix damage. We know this to be true when dealing with classical aging, where it's harder to reverse disease than it is to prevent it. With some of these biological age clocks, what you're measuring is the whole history of a person being alive.
“With some of these biological age clocks, what you’re measuring is the whole history of a person being alive”
With the rate of aging estimated, you're getting a more intermediate effect. And that intermediate effect is absolutely correlated to health outcomes.
So as someone who is trying any type of intervention, whether it be diet, nutrition and exercise, they can look at their rate of aging and then find out what is the most optimal strategy for them by comparing markers even within three months.
LB: That's really valuable for the self experimenter.
TruDiagnostic Biological Age Test Kit Includes Telomere Age
Extract of the TruAge Complete telomere based biological age estimate.
LB: So far we’ve discussed three biological age values. Extrinsic, intrinsic and rate of aging. We won't talk about today, but we’d like to also mention that there's also a telomere based estimate that TruDiagnostic offers through the TruAge Complete test kit.
A theme has been building through this conversation about third generation biological age clocks. One innovative area of development for such clocks is a new and very powerful capability to be predictive of specific disease outcomes.
Tell us briefly about how TruDiagnostic test kitsare starting to connect the dots to certain disease risks.
Biological Age and Age Related Disease Risk
RS: We're lucky enough to have biobanks that have taken samples from 30 years ago. This enables us to look at how their epigenetic methylation correlated to the health outcomes that they faced.
A good example is our validation with the Framingham Heart Study cohort. We found that those people who are aging anywhere below one year per year generally would have a 50 to 50% less chance of dying over the next seven years. They also have a 54% decrease risk of a chronic disease over the next seven years.
But those people with an aging rate above one year per year, so called ‘fast agers’ were overall 65% more likely to die. That's obviously just talking about mortality.
“People who are aging anywhere below one year per year generally would have a 50 to 50% less chance of dying over the next seven years”
We have also found that the rate of aging marker is predictive of things like grip strength and muscle mass, as well as IQ and mental processing speeds, and even facial aging.
We have some really great composite images of how people age in our cohort, grouped according to their rate of aging, and even at age 45, the 10 slowest aging members of the cohort look to be maybe 20 years younger than the same individuals at 45 with a fast aging.
The Future of Biological Age Testing
LB: We love to talk about tools for disease risk on Longevity Blog. We believe there is significant value in thinking ahead about your personal risk, and that by analyzing that risk profile you can get 10 to 20 years ahead of the age-related problems you're going to develop.
As your team looks forward, what is going to become possible for TrueDiagnostic in the near future? Your company is actually very fast moving - you're putting out new reports every few months - tell us one or two new and exciting capabilities that are coming in the next year.
RS: There are a couple of things that I'm really excited about.
TruDiagnostic can analyse your epigenome to reveal much more than just your biological age. They are adding new reports regularly, including a recent ‘weight loss’ report to better understand how your body might respond to calorie restriction, for example.
One of which is a project we've been working on for a long time - what we consider a fourth generation algorithm. In order to do this, we want to include what we call multiple levels of the “multi-ome”.
This is a very complex process. We already have talked about how challenging working with longitudinal data can be, and how it is really important to remove confounding factors. But if we can also add to that longitudinal score more depth on those physiologic measurements or those molecular measurements, then we can get an even clearer composite image.
We are in collaboration with Harvard and have been working on a multi-omic clock for probably two years, now. It will include genetic data and will include some micro RNA data, as well as epigenetic, proteomic data (peptides and proteins in the blood), and then lastly, metabolomic data (metabolites in the blood). We will also expand it to to include 75 blood related biomarkers (up from 19 in the current version).
Measurement will take place over four different time points, which should allow for a biological age clock that is hopefully unparalleled, in terms of its accuracy and precision. So we're really excited about that.
LB: I think it is a very exciting version of the future capability of biological age clocks.
Ryan Smith Co-Founder at TruDiagnostic’s Longevity Strategy
Wrapping up our interview, one thing we always ask our guests is this - knowing all the developments upcoming in longevity technology, what are you doing everyday to look out for your own health and longevity? Tell us part of your longevity strategy.
RS: One thing I'm ashamed to admit now is that previously, I was, I would say, a big skeptic of the importance of meditation and mindfulness. I used to think, you know, am I doing this right? Is this really meditation? Is this even working?
Stress has a “Major Impact” on Biological Aging
The impact of stress and emotional regulation on aging and the aging process is incredibly strong. It is way stronger than I would have ever anticipated. It still baffles me that someone's emotional regulation can have such a major impact on their biological aging process.
Stress, sleep, diet, exercise - these all impact biological age results. Want to learn more? Check out our interview with Dr Robert Lufkin on YouTube here.
We're still not really sure how this is mitigated. I think a lot of people might say it's regulated by cortisol or some of these other stress hormones. But I can tell you that it has a major impact. And so one of the things I really try and do is to spend some time on mental health. I was never that way previously. But you know, seeing the results I've seen and the correlations I've seen, I've definitely done a 180.
In addition to that, from an interventional approach, I tend to be a very big fan of rapamycin and mTOR inhibitors. In all the aging interventions that we know about now, this one is probably one of the most exciting for wide scale application.
Lastly, even though I am probably not the best at actually implementing this into my own life, I think periods of fasting, fasting and caloric restriction are also some great strategies which have very little downside and have the potential to have really good longevity benefits.
LB: As that's fantastic, Ryan, we're going end the interview there. Thanks so much today. We really appreciate your time.
RS: Thanks for having me as guest on Longevity Blog!
Trudiagnostic Discount Code!
A part of our mission is to make your longevity budget stretch further.
You can save 12% off TruAge Complete or TruAge PACE biological age test kits.
se the code longevityblog at checkout and save!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
What is the Most Accurate Biological Age Test? An Interview with Ryan Smith of Trudiagnostic (Part 1)
Trudiagnostic review: Most accurate Biological Age TEst
How accurate is the biological age test you are currently considering?
Great question, but you also need to ask - how precise is the biological age test?
What do we mean by this? If the difference between these two terms isn’t 100% clear to you, you’re definitely not alone.
The fact of the matter is, choosing the best biological age kit for you is not a straightforward decision, and with more test kits arriving on the market each month - you’ll be glad to know that Longevity Blog is here to help!
In this post, we cover the basics of ‘accuracy’ vs ‘precision’ and in our TruDiagnostic review, reveal why their kit is the best biological age test currently available (plus we score you a discount to purchase one!).
Biological age test technology is moving fast
When investing in a biological age test kit, you’ll want to choose the product which has the best accuracy and precision. What does this mean? We’ll discuss this in detail in today’s interview.
Just like most of the longevity technology sector, biological age testing is advancing quickly.
And while we’ve previously reviewed some biological age testing companies, it is very important to keep you informed of the latest developments.
We have two very important updates for you.
Firstly, did you know that we’ve now moved into the third generation of biological age clocks?
What does that mean? These are algorithms which use longitudinal data collected from the same individuals to see determine how aging occurs over time.
Secondly, many of the first and second generation biological age clocks may have good accuracy, but they are not necessarily great at precision.
To illustrate what this means, if you were to send off three of the same saliva or blood samples to your biological age testing facility of choice, a highly precise laboratory would provide you the same biological age estimate each time. But if they don’t have great precision, you could get three different results.
A graphical representation of accuracy and precision (credit: TruDiagnostic).
For example, if your age is 35 and you get a biological age of 33, 35 and 37, that test kits only has a precision of around 2 years.
So, which results do you believe?
You might be surprised to know that many of the offerings on the market offer precision within 2-3 years.
What does that mean? It means that if you measure your biological age, test an intervention through a self-experiment, and then test again (which is how we recommend you use these kits) - your actual results could get lost in the ‘noise’ with low precision kits.
If this concerns you (and it should!), then you’ll be very interested to hear what our latest interview guest has to say…
TruDiagnostic review video: Hear it straight from the expert, Founder Ryan Smith.
latest developments in Bioaging with trudiagnostic CO-FOUNDER RYAN SMITH
Ryan Smith the Co-Founder and VP of Business Development at TruDiagnostic.
But don’t let his ‘business’ title fool you - he is exceptionally knowledgeable on the science behind epigenetic testing.
Ryan is a biochemist who founded Tailor Made Compounding, which became the 4th fastest growing company in healthcare in the US at the time.
In late 2019, he saw tremendous potential in epigenetic testing and analysis and co-founded TruDiagnostic, who now offer once of the most accurate and precise biological age test kits on the market.
Today, we ask him to walk us through these important developments in biological age test kit technology. Strap in and put your thinking caps on!
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with TruDiagnostic, we have a negotiated a 12% off coupon code for our readers.
Use the code longevityblog at checkout and save!
This interview was conducted in August 2022 over Zoom and is an audio transcript with edits for clarity, brevity and correctness.
How do you estimate biological age?
Ryan Smith, Vice President of Business Development at TruDiagnostic is a wealth of knowledge on the latest developments in biological age testing. In this interview, we first explore the development of biological age ‘clocks’ and what it means for these clocks to be accurate and precise.
Longevity Blog (LB):
Ryan, thanks so much for joining us today. We have a very common question that we'd like to ask you to kick things off. And it's an important one, lots of people ask it:
How do you determine your biological age? Could you give us a general answer?
Ryan Smith (RS): Certainly! I think that the answer has changed throughout time. The search for biological age has always been important because of something called phenotypic variation - there's a lot of difference between how people in the same chronological age group age differently.
This definition of biological aging, searching for how the body is aging was very crude initially. Things like the number of your chronological age plus the number of packs per year you smoke, as a biological age. But as we've gotten more sophisticated they’ve culminated in epigenetic clocks, which are probably the most sophisticated methods to determine biological age.
Even these have a little bit of a history where they've continued to improve. Right now, what we're essentially doing is creating algorithms to predict someone's biological age. And we do that by having a cohort that we train these algorithms and then a separate group as a validation cohort. That's what we've done with epigenetic clocks, and it's why they're generally the most predictive of negative age related outcomes and why they're so powerful.
What is an Epigenetic Age Clock?
Epigenetics instructs your DNA on how to be expressed. All cells contain all of your DNA, but how do they know to be a liver cell, or a brain cell or a skin cell? Epigenetics is where this information is stored.
LB: You've mentioned “epigenetic clocks”, briefly remind our audience what these are.
RS: Epigenetic clocks are essentially a biomarker measurement. Age clocks can be created using any type of data set, but here the data that we're measuring is an epigenetic methylation.
For those of you who aren't familiar with epigenetics, it essentially is the regulation of your DNA.
Every single cell on your body has the same DNA sequence, it's what makes it individual to you. But how that DNA is expressed is different from cell to cell. It's why your skin can behave like skin cells and your heart can behave like heart cells. This is determined by what genes are expressed or turned on.
What we're measuring is DNA methylation, which is the off switch, generally, for most of those DNA expressions. We have a lot of DNA methylation in our cells, with over 29 million spots in each cell, which can be methylated. And every cell is different. So it's a lot of data.
Epigenetic clocks have been created by seeing the differences in aging at these different locations across individuals. And then creating a predictive algorithm to see if we can predict that change with age and see how close we can get to variables, like someone's chronological age, for instance.
How Do You Determine Biological Age?
Methylation of the DNA is the on or off switch for DNA expression. There are over 29 million ‘CpG’ sites in your genome where methylation occurs. The patterns of methylation change with aging, and therefore they make an excellent predictor of how old you are biologically.
LB: Biological age clocks have been around for about a decade, and they’ve advanced very quickly over the last few years.
Can you introduce us to this concept of the “generations” of epigenetic clocks that have emerged and an approximate timeline?
RS; The first ever biological age clocks came out in 2011, with the first really widely applicable clocks created by Dr. Steve Horvath at UCLA in 2013.
I will go on record by saying I think he might be nominated for a Nobel Prize for this work. It is really groundbreaking, because, for the first time, we're able to read with a very high accuracy: the age of someone's body.
The clock was originally created by looking at those epigenetic methylation changes across a few thousand patients and looking at what markers were most significantly changed with age. Some locations might have no methylation at young adulthood, but as as we get older, significantly more methylation or vice versa.
That's how he was able to create this predictive algorithm. But it was trained to predict someone's chronological age. Originally, it was used for really interesting applications, but not necessarily health applications.
One example is collecting DNA at a crime scene to see how old a criminal might. In the case of the refugee crisis with Syria, it was used to see if people were adults or minors, and therefore eligible for asylum.
How Does Biological Age Testing Work?
Our Founder Nick has tested the TruDiagnostic product, and was very impressed with the wealth of knowledge TruDiagnostic provided through just a few drops of blood!
LB: But the new applications in health began to emerge, as ‘older’ individuals were connected to poorer health outcomes. Tell us about this transition.
RS: The research field started to notice a pattern, which is that those people who were older with this test than their chronological age, were at significantly increased risk for negative health outcomes.
While those people who were younger than their chronological age, were protected against those same outcomes.
They discovered, for example, that being seven years younger biologically than chronologically reduced the risk of morbidity and mortality by 50%. So that was the first generation of age clocks.
Generations of Biological Age Test “Clocks”
LB: That's a little bit of a complicated concept that you're introducing here, so let’s make sure we make this very clear for the reader.
First generation clocks weren’t developed to predict risk of poor health outcomes, but in their application were discovered to be capable of doing this.
Now, with this realization, we begin to see the development of ‘second generation’ clocks which are designed to be predictive of age related health outcomes. Is this correct?
RS: Exactly. An important concept here is “hazard ratios” for disease. This is essentially the likelihood of developing a particular outcome. You can have hazard ratios for anything. You know, that hazard ratio for it raining, for instance.
For disease, the higher the hazard ratio, the higher your likelihood. Ideally, the bigger the change in the biological age, the bigger the change in hazard ratio. That's exactly what we're seeing as these biological age clocks get better. “Second Generation” clocks are now being trained not on chronological age, but on biological signals.
LB: Have the inputs to second generation clocks changed? Are there new variables which are being considered in the training datasets with second generation clocks?
“the key characteristic of the third generation of biological age clocks is using ‘longitudinal’ data sets, which follow the same person over time”
RS: In the second generation clocks, we have started to measure things like your blood based biomarkers that we know change with age.
For example, your red cell distribution width, your immune cell types and distribution, or your serum albumin. These are all things that change as we get older.
Then, for third generation clocks, which is really where we're at now, they did the exact same thing, but they did so longitudinally. So instead of looking at a lot of different patients over a lot of different time points, they looked at the exact same patients over a long time period.
By analyzing data longitudinally, we are able to get rid of other confounding factors, things like environmental exposures. For example, if we get these from a biobank, the amount of antibiotics that someone was exposed to 40 years ago might have been a lot less than what we're exposed to now. And vice versa. Another example is leaded gasoline instead of unleaded gasoline.
By looking longitudinally, you can sort of factor those things out, because you can sort of assume that the population you're looking across time has had similar exposures, especially if they're living in a similar area. And so what we're starting to do is to now get rid of all of these confounding factors which might be taking away sensitivity and specificity from the biological signals of aging.
A graphical representation of the concept of generations of biological age clocks. For more information, you can read this scientific study.
LB: So the key characteristic of the third generation of biological age clocks is using ‘longitudinal’ data sets, which follow the same person over time, and understanding how that biological age is changing over time based on environmental factors and tracking blood based parameters? Second generation clocks are missing this ‘longitudinal’ data.
RS: Correct. There is really only one third generation algorithm that currently exists, DunedinPACE. This clock uses 19 blood related biomarkers from a longitudinal study, where they tracked gum health, for instance, and leukocyte telomere length, which has classically been a very popular marker for biological age.
Biological Age Tests: Accurate or precise?
“Precision is very, very important, especially on a personalized medicine aspect. If you have a wide degree of technical variation, you’re just not sure if the change you’re seeing is real biologic change, or if it’s just noise.”
LB: TrueDiagnostic have differentiated their biological age test from other providers by offering the market’s only third generation clock.
Tell us why this algorithm is better for biological age predictions in very simple terms.
One of the things you shared at pre-interview is the ability of this clock to consistently make the same predictions off the same sample data. Maybe start there.
RS: We've already talked a little bit about how to judge an aging clock’s accuracy, right? Which is generally more predictive of negative health outcomes? The other thing we want to always talk about is precision of the algorithm. We want it to be both accurate and precise.
This has been a very big problem, actually, for these epigenetic clocks to date. One of the reasons I think early adopters have been a little bit disillusioned with these second generation tests is because they've had wide variability.
For instance, even with Dr. Horvath’s original algorithm he created in 2013, if you took the exact same sample and tested it twice, you could have up to 3.9 years of variation from even the same sample. That's a huge problem, because if you're looking to use this for reliable information to judge things like interventions, you wouldn't be able to test within a period of 3.9 years in order to get a statistically significant outcome.
Precision is very, very important, especially on a personalized medicine aspect. If you have a wide degree of technical variation, you're just not sure if the change you're seeing is real biologic change, or if it's just noise.
What is the Most Accurate Biological Age Test?
The ICC (intraclass correlation coefficients) score represents precision. How consistent is a given biological age clock at reproducing a biological age prediction off of the same sample? At far right is the algorithm used by TruDiagnostic, showing how precise the algorithm is compared to other methods.
LB: Okay, so there's some complicated concepts you're talking about there, we're discussing the difference between precision and accuracy.
You've gone into some detail about some of the limitations of second generation clocks, and where this newer third generation has a bit more precision.
Generally, when people are trying to make a decision about a biological age test, they'll ask a question that's a bit more simple, or perhaps even naive of some of these details between terminology for precision versus accuracy. They're going to ask, “Which biological age kit is most accurate?”
If you're talking to that layperson, what do you tell them?
RS: Whenever you get the results of any biological age test - you want it to be informative about why you think they asked the question in the first place. I think for most people it would be - Why do you want to quantify aging in the first place? The answer is that biological age is the biggest risk factor for most chronic diseases and death.
So if you want to quantify a risk factor, usually, it's because you want to change it right? And so in order to measure that, you really want it to be predictive of outcomes. So the most accurate clocks are going to be the ones that get higher when you're going to have worse outcomes for all age related markers. And as they get lower, you're gonna have more positive outcomes for all age related markers.
And the way that we measure that is called a hazard ratio. What is your likelihood of getting a particular disease if you're aging at a rate of one versus if you're aging at a rate of 1.1? And in General, the higher the hazard ratio, the more predictive and so I would measure accuracy by its ability to be associated with health outcomes.
There are Different Types of Biological Age: Extrinsic vs Intrinsic
An example of an intrinsic biological age test kit is GlycanAge, which tracks inflammation in your body by analysing your glycans. What are glycans? How can you use intrinsic age to self-experiment, why not read about it here?
LB: Often, biological age is discussed as if it's one number. But one of the things that we've learned through engaging with your testing kit and platform is that there's two big categories of biological age.
Extrinsic biological age and intrinsic biological age. So far, we've been talking about extrinsic biological age.
Tell us about intrinsic biological age.
RS: At the cellular level, biological age measurement is different in every cell. Your skin cells are going to be very different than your heart cells, in terms of what genes are turned on, and turned off. So ideally, if we were to do this test, we would do it on a single tissue type and that would be the most precise and accurate way to develop an algorithm.
But the problem is that for most of our body, we have a whole combination of different tissues making up any given organ. In our skin, we might have keratinocytes, cells, as well as fibroblast cells. In our blood, the majority of the DNA is from our immune cells. These include things like CD8 T cells and CD4 T cells, your monocytes, your basophils - you know, all of these different cell type markers.
TruDiagnostic’s Immune Age ReporT: An Intrinsic Biological Age
LB: So in simple terms, intrinsic biological age can be based on different cell types representing a given organ or systems in the body.
In your TruDiagnostic report, you've focused on the immune system for the extrinsic biological age.
There's this important concept in biological aging known as immunosenescence, which is the decline of immune system age. Talk to us about this process and how looking at an intrinsic age can help us understand how we are aging biologically.
From a TruDiagnostic ‘Immune Age’ report, a graphical representation of immunosenescence.
RS: As we get older, one of our most important immune organs, the thymus, starts to degenerate. We lose thymic volume and as a result that changes the amount of immune cells which are circulating in our blood.
This means the immune system generally becomes worse at doing its job, and isn’t clearing things that are not supposed to be in the body. Being able to quantify immune cell changes allows us to quantify the aging process in a different way.
We can gain a bit of insight into how the immune system is aging. One important measure is the ratio of CD4 to CD8 T cells. We would usually see this decrease as we get older - so the decrease in this ratio can be used as a snapshot of your immune system’s aging.
LB: Would it be accurate to say that extrinsic biological age is more responsive on a short term basis to interventions?
RS: Yeah, certainly. I think that the answer is we definitely see more variation on a day to day basis. These changes that are happening in your blood are happening at a very large scale and new changes are some things that we can detect. This biomarker can be trained for a wide variety of things.
LB: Thank you, Ryan.
TruDiagnostic are also providing an estimate of how fast you are aging….
Read Part Two of the Interview Here
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Boosting the Immune System with IV Therapy - Does It Help?
Amidst a Global COVID-19 Crisis, Immunity is on Our Mind
In this post I’ll cover:
The basics of IV therapy
An experiment I ran with an immune boosting IV therapy
White blood cell blood tests
Review of the data I collected
Making the best conclusion we can on the value of IV therapy based on the data collected
It just so happens, I recently ran an experiment with immune IV therapy to answer - is an immune boosting IV treatment worth it?
A quick video sharing the experience of getting an IV therapy at NextHealth in West Hollywood
Most of us have had an IV in our lifetime. They are exceptionally helpful for delivering hydration and electrolytes to patients in-hospital. IV stands for ‘intravenous’, as they function via the insertion of a sterile catheter into the vein (most commonly in the arm or wrist). Sometimes, in addition to hydration, they are used as a method of ‘infusion therapy’ where, for example, medication is delivered intravenously.
Traditionally, IVs were only delivered in hospitals, but then after a time, shifted to outpatient clinics, and now are populating health & wellness centres around the world. Chances are, if you Google for an “IV clinic" in the US, Australia or Europe - you’ll find one near you! In each instance, a trained nurse is the most likely the person who will insert the catheter and set-up the infusion treatment.
IV Therapy at NextHealth - Super Immune
I recently undertook my first ever IV therapy (outside of a hospital) at NextHealth in West Hollywood, Los Angeles. After undergoing a micronutrient test to inform my selection of treatment, I settled on trying out the Super Immune IV therapy. My motivation for this was that on my previous long-haul roundtrip from Sydney to Los Angeles, I became quite ill upon return. So this IV therapy caught my interest during a following roundtrip Sydney-LA about 2 months later.
Super Immune IV - the Claim
The Super Immune IV claims to ‘supercharge’ the immune system with Vitamin C, Magnesium and Vitamin B5 plus Selenium, Taurine, and L-lysine. I took a photo of the information NextHealth provided to me on the contents & benefits of the treatment.
Forming a Hypothesis: Immune IV Therapy - Does it work?
Now, being the biohacker enthusiast I am, I naturally decided to undertake an experiment in order to try to measure the impact the Super Immune IV therapy had on my immune system. With any good experiment, we must form a hypothesis, design a framework for testing it, collect relevant data, analyse these data and form a conclusion. So let’s start with - what was the hypothesis?
Hypothesis: the Super Immune IV will measurably boost my immune system and keep me from getting sick during my international travel
The Experiment: Two Long Haul Roundtrip Flights from Sydney to Los Angeles
As I mentioned above, I completed two long-haul, roundtrip flights from Sydney to LA. Both lasting 7-8 days. The first was in November 2019 (Trip #1) and the second was in January 2020 (Trip #2). During both trips, within 4 days of the first flight, I completed a comprehensive panel of blood tests (one at NextHealth, one at the Health Nucleus). Trip #1 had no Immune IV. Trip #2 had an Immune IV therapy on Day 2 of the trip (3 days prior to the trip’s blood test).
There are many factors that could influence the results of this experiment, but as with nearly every biohacker experiment this is always the case. In fact, it is a fundamental limitation of running self-experiments that they cannot be perfectly controlled due to the sheer complexity of our biology and its interaction with our environment. This doesn’t mean one should not do their best to provide a controlled environment! It just means we need to mindfully interpret the results of the experiment.
However, I took a number of measures to provide the best control possible. Diet was unchanged. Sleep was very similar on both trips, with ~7 hours of relatively poor sleep on the flight over (according to sleep tracking data). I also employed the same jet lag adjustment strategy that I have developed on both trips. Neither had more than 1 glass of alcohol (wine) intake within 2 days of the blood tests. Both had moderate levels of exercise (plenty of walking, some light running).
Caption: Step 1: Chill in sweet chairs. Step 2: Get your arm warmed up. Step 3: Get skilfully stuck. Step 4: Pump in the goodness! Step 5: Relax! (It takes about 30 minutes)
Understanding the Data Points
For the layperson, there is a need for us to first dive into what the data I plan to share represents. The same data was collected for both Trip #1 and Trip #2.
White Blood Cell Count (WBC)
White blood cell count (WBC) represents the total number of leukocytes in a volume of blood. Leukocyte is just fancier way of saying white blood cell, which are the cells of the immune system that protect us from infectious disease and foreign material (e.g. toxins, allergens).
If WBC count falls below the standard reference range of 4k/uL, this signals that the supply of white blood cells has been depleted. This is most commonly caused by an infection, but can also be the result of chemotherapy or radiation treatment (hence why many cancer patients have compromised immunity). If you are noticeably fighting a viral or bacterial infection, it is likely your WBC will fall below this value, before rebounding as your immune system ramps up.
A selection of white blood cell types. Source: unknown
White Blood Cell Differential
Whereas the WBC represents the total number of white blood cells present per unit of blood, the differential blood count provides a breakdown of each type of white blood cell. This is most commonly used in medicine to search for any abnormalities in the overall populations. Differentials can be useful in the diagnosis of infectious disease, allergic reactions and during monitoring for adverse impacts from certain drugs (e.g. cytotoxic ones used in the treatment of cancer).
There are many excellent sources of information on the ‘basics’, and in my background research I found Medscape to be a particularly useful source.
Neutrophils - the most common type. Neutrophils function by travelling to the site of an infection to release enzymes to ward off viruses or bacteria which are invading the body
Lymphocytes. These search and destroy machines breakdown into two types:
B-cells fight exogenous (those coming from outside the body) bacteria, viruses or toxins.
T-cells target the body’s native cells in the case that they become infected by a virus or those that become cancerous.
Monocytes remove foreign material, remove dead cells, and boost the body's immune response.
Eosinophils fight infection, inflammation, and allergic reactions. They also defend the body against parasites and bacteria.
Basophils release enzymes to help control allergic reactions and asthma attacks.
This is a heap of new information for most us, so here are few key take-aways for understanding the upcoming results and discussion:
A fall in WBC below the reference range of 4k/uL is:
indicative of an infection (in my case on Trip #1, a respiratory virus)
most often due to depletion of the neutrophils who are ravelling to the site of an infection as first responders
The standard reference range expects neutrophil count to be greater than 1.5x10E6/uL; for me, a value of ~2.4x10E6/uL is baseline.
Interpreting the Results
In addition to the two WBC and differentials tests I had performed in November 2019 (Trip #1) and January 2020 (Trip #2), I have also included data from May and August 2018, to provide baseline measurements. During both of these baseline measurements I was healthy and without an immune system compromise.
White Blood Cell Count (left-hand axis) and White Blood Cell Differential (right-hand-axis) over four blood tests. Trip #1 data is “Nov-19”, where I became unwell. Trip #2 data is “Jan-20” where I received the Super Immune IV therapy at NextHealth.
From the provided chart, a few observations can be drawn
Baseline values for WBC and differentials are steady (May-18, August-18), evidence of a good set of control data
There is a clear drop in WBC, Neutrophil and Monocytes in Nov-19 (Trip #1)
Trip #1 WBC values fall below the reference range values, indicative of the viral infection
Trip #2 Neutrophil values are about 15% below baseline
Trip #2 WBC, Lymphocyte, Basophil values are in-line with the baseline values
Trip #2 Eosinophils are 3.5-4x baseline value
Interpreting these results is complex, but given my unique perspective as the experimenter, I offer the following supplementary information and observations.
WBC which is indicative of the overall immune system’s robustness are higher during Trip #2 than in Trip #1
Neutrophil count during Trip #2 is not in-line with baseline, suggesting it is possible that my immune system was being challenged, but not overcome (as is expected during international travel)
The increase in Eosinophil (Eos) count in Trip #2 is probably best explained by my legs being covered in angry red scrapes from a trail run where I got lost and had to scramble through bracken fern two days prior to my drip (ouch!). Recall from the above these white blood cells fight inflammation and allergens (those angry red scrapes!).
Point #3 suggest that there would be a downward revision of WBC to approximately 4.7k/uL for the purposes of comparing it to baseline and Trip #1 (adjusting WBC to not have the cofounding signal from the Eos elevation). This still leaves the WBC similar to the baseline values of 4.9 and 4.8 k/uL.
Discussion: Does the data support getting an Immune IV treatment?
So, let us return to the hypothesis - that my intake of an IV immune therapy would measurably improve my immune system during my long-haul flight and international travel and I would not get sick.
We so far have discussed one primary source of data and analysed it in this context. Overall, based on my ranges of 'normal' from my historical blood tests, the results after my NextHealth Immune IV, and Trip #1 where I became ill from the travel, it does appear there was a measurable improvement in my immune function on Trip #2.
While not perfect, I choose to wear a facemask whenever I travel through airports. These are not guaranteed to provide effective protection from contagious disease, and are advised against by some medical experts. It is my personal opinion that they do provide some measure of protection when compared to not wearing one.
However, this it is difficult to make the conclusion that the Immune IV kept me from getting sick with high confidence. I could have simply picked up a particularly nasty virus on the way to/from LA on Trip #1 and not on Trip #2. In this scenario, the Immune IV treatment could arguably have little to do with the outcome or any of the apparently measurable difference between the two.
Instead, I offer that it is more valuable to draw a different category of conclusion on the subject of whether the Super Immune IV is worth it. To do so, we need to return to both (a) the fundamentals of international travel, (b) the outcome I desired (to not get sick) and (c) the value of the outcome versus the cost.
With respect to (a), it is known that getting poor sleep, experiencing timezone changes, and being exposed to numerous pathogens (in the airport, in the airplane) undoubtedly challenges the immune system. It is commonly accepted that one should take action to protect themselves when travelling for these reasons.
Secondly, and in my view, more importantly, (b) - I did not get sick on Trip #2, which is the outcome I desired. Becoming ill on return after Trip #1 was miserable, cost me time at work, and put my family and friends at risk of contracting the pathogen I was carrying.
The Overall Conclusion: Immune IV Therapy is Worth it (For Me)
Given the experiment, data and resulting discussion, I offer the following conclusions:
1) It is completely possible and perhaps probable the Immune IV therapy boosted my immune system and kept me from getting sick on Trip #2
2) Getting an immune IV therapy is an appropriate risk management, strategy for international travel
This latter conclusion is based on the principles of risk management, where one weighs the nastiness of the outcome against the cost of managing the risk. In this context (c), I’d argue the IV treatment to be well worth it at $189USD.
As an outcome from this experiment, my personal choice will be to continue to drop into NextHealth on my long-haul trips to the United States and get that IV goodness dripped into my vein! If you’re a travelling businessperson with similar level of resources (IV treatments are relatively affordable to you) and level of risk (becoming unwell is quite costly), you would likely also benefit from partaking in immune boosting IV therapies.
I’ll be sure to collect additional WBC and differentials data on my next trip to the US and post a follow-up blog to accompany this one. Be sure to subscribe to be notified when I do!
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