ONE Tiny Blood Spot = HUNDREDS (!) Of Biomarkers, Age & Disease Prediction With Dr. Matt Dawson

My name is Ben Greenfield, and on this episode of The Boundless Life Podcast, your DNA makes it up about 20% of your health outcome, but the other 80% is what you do, what you eat, how you sleep, your stress levels. With epigenetics, you're measuring that, that other 80%. You're actually looking at how much every gene is turned up and turned down. What we can predict with epigenetics is limited by our imagination and the size of the data set.

Welcome to The Boundless Life with me, your host, Ben Greenfield. I'm a personal trainer, exercise physiologist, and nutritionist, and I'm passionate about helping you discover unparalleled levels of health, fitness, longevity, and beyond.

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My guest today, Dr. Matt Dawson, physician, entrepreneur. I don't know what you call yourself, man. You're kind of both and also an athlete now, a competitive endurance athlete by the sounds of it. Tell people about this adventure you just got back from.

Well, first off, I love your sweater. Your sweatshirt says Dad. I think I'm just going to call you Dad for the podcast because that'd be fun. Maybe, actually, I'll just throw this I'm in right now.

This is the most expensive sweatshirt I own. I was at a spa in Portugal and the weather was colder than I thought the weather was going to be in Portugal. And so, I went downstairs and I'm like, "I need to buy a sweater from the spa at this hotel." And, I just grabbed this one because it looked like the cheapest sweater in the joint and put it on my hotel account. And, as I was checking out, realized I'd spent $350 on a sweatshirt that says "Dad" on it. And it literally feels like a cheap Champion sweatshirt. I think I just paid for the brand.

So it was like $50 for the sweatshirt and then $100 per letter for your DAD there.

So that's great. Yeah, exactly. But you had a more exciting adventure than a spa sweatshirt.

Yeah. So the Kilimanjaro. So it was almost a year ago, probably 9 to 12 months ago, somebody reached out to me and said they were going to try this Guinness world record group speed attempt of up and down Kilimanjaro. And I thought, I am definitely not that fit, I am no Ben Greenfield, but that sounds fun. So I haven't really trained for— I've done a couple Ironmans, but I'm extremely slow, kind of barely finishing. And but it was like so much fun. I spent 9 months really training and seeing how my body would respond. I basically built an AI coach for myself that I would feed in all my True Health data, all the stuff they're going to talk about, all my training data, my lactate threshold stuff, and It was just cool. Yeah, I had a blast like watching my body respond. And in the end, I think there were 34 of us that tried. We needed 4 of us to finish under a time to get the group world record, and 5 of us did. I think there are a couple more that may have came under, but yeah, I was, I was part of that group. So I got a new Guinness World Record for Kilimanjaro up and down.

Congratulations. That the, uh, the AI training thing is interesting. So did you just kind of like upload all of your data and say, "Here's the fitness level I need to be at and the mountain I need to climb in X number of months.

Tell me what to do every day." Yeah, the exact route, the exact kind of set. We did 7 days of kind of acclimation before the first week. We summited twice. So, the first route, the second route, which one we're taking, where my fitness was at. It gave me tests to do like where's my muscular endurance, where's my cardiac drift, where's my VO2 max,. And we— I got all of that in there, all of my biometrics, my health stuff, and then come up with the plan, come up with the supplement plan, come up with everything. And every day I would upload my workout that I did. It would adjust. Every couple weeks we'd do tests, it would readjust based on how I'm doing. And it was the first time I've ever trained for something or went through a sports season without getting injured, without overtraining, because I just really listened to it, follow the plan. And, and in the end, even the climb was a science experiment. Like, I still was not— the people who were on the climb with us, there were Army Rangers, Special Forces, Delta Force guys, like famous ultra marathoners and, and adventure folks, and they were way stronger than I was. But I was actually the first one to the top because I was so dialed into like the science of— I knew it's really an eating contest with a lot of hiking, but I was dialed into like what calories I could take, how many which macronutrients at which heart rate, like what could I take in at 125 versus 135 versus 145. It was just all science. This is so much fun.

Okay, so the, uh, the professor beats the meathead. The, uh, the app, or I guess like the LLM that you use for that, I mean, where my mind goes is, couldn't you kind of like take that entire set of training that you did for those months and like vibe code that into an app that would do the same thing for other people?

Yeah, absolutely. And it progressed. And so, and also we were creating— including us— and we were creating kind of a beta product of something that does this, not necessarily for fitness but all the biomarkers. So I was using that a little bit. Also, I started out using just a ChatGPT folder where I could keep everything, but then I ended up progressing and switching when OpenClaw came out, and there was the whole craze around OpenClaw in January. And so my final kind of coach where I settled on was OpenClaw, using Opus 4.6 as the base, was the final thing. So it kind of progressed how I was using it. And I mean, every month, the cool thing is every month it got better as the different models got better. But that was the final version was actually an open call agent that I just talked through via Telegram.

Sign me up for a beta user if you ever develop that into an app. That sounds super funny. It almost sounds like it would almost be able to reverse engineer motivation into you to sign up for an event just because you know you'd have a pretty precise script written for preparation.

2 things about that. One, in the next couple of months, we are releasing something, True Diagnostic, that is not exactly that, but it would function that way, but it's more geared towards optimizing your pace of aging and all that with True Health. But number 2, the guy that organized that trip, he organizes these really incredible trips and adventures. His name is Dave Pickles. So, great name, not made up. Dave Pickles. He's in Great Britain.

Sounds like a badass adventurer name.

TikTok. Well, the funny thing is, like, he sounds like he's from a children's story, uh, but yeah, he was like ex-Delta Force. I mean, he is a, he is a badass, uh, even though it sounds— yeah, he's incredible. The stuff that he's done is amazing. But he has like, um, uh, I don't know if I can talk about this yet. He told me about— there's a, there's an incredible adventure race around in Africa, I'll say, because I don't think I am supposed to talk about it, next year, um, that he's going to release really soon., and he wants to partner. Like, I told him about the app that I'm building and stuff, and he wants to partner and kind of use that with all of his adventure things. So if anyone is into that stuff, you should totally go to, like, check out Dave Pickles. I think it's maybe like— yeah, just Google Dave Pickles, and, um, he's probably going to have something really cool like that in the future. But he does such a phenomenal job of organizing it. I mean, he— there were some people in our, in our group on the first trip, not the world record one, that you wouldn't think would be able to necessarily do this. And he just got everybody to the top just because of the level of organization.

Nothing like a little pickles motivation. Interesting. You mentioned True Diagnostic a couple times. I mean, people who have been longtime podcast fans have probably heard you 4 or 5 times on this podcast. When we first met, you were running Wild Health, a physician network for precision medicine. I know that you've moved on, And now, you're at the helm of this company, True Diagnostics. You got the TrueAge test, you have the True Health test, and these are very unique tests. So, I would just love to hear what the full update is on the field of epigenetic testing, what it is when it comes to helping people understand that. But let's start there. What is the quick version of epigenetic testing?

And why I kind of moved from Wild Health. So, I founded Wild Health and was a CEO. It was acquired by a publicly traded tech company. We built kind of some AI tech to take millions of data points, get precision medicine recommendations. So I stayed on as CEO, but then about 2— and that was about 3 and a half years ago when it was acquired. About 2 and a half years ago, I got a call from True Diagnostic, and they were— they wanted to show me some science they were doing with Harvard. At first, it seemed too good to be true, but after about a week of looking into the science, I became convinced it was the most exciting thing I'd ever seen in science and medicine. And that's what prompted me to leave Wild Health. So Wild Health was based on genomics, was really the core, like precision recommendations or personalized recommendations based on your DNA.

Just to explain that to people, this would be something similar to what, I don't know, SelfDecode, 10X. I think 23andMe tried to do it at one point, but this is just basically getting your DNA tested and getting health recommendations based on that DNA.

That's right. And your DNA makes up about 20% of your health outcome. And so at Wild Health, we'd also add, um, like lab tests and other things to that. But epigenetics is the other 80%. So you're born with a DNA, that's 20% of your health outcome. But the other 80% is what you do, what you eat, how you sleep, your stress levels. With epigenetics, you're measuring that, that other 80%. You're actually looking at how much every gene is turned up and turned down. So it's not what genes you have, how are you expressing them? And that's just a much richer data set. I remember when I— this, this Harvard study, for example, they got excited about. They were looking at— so everyone's familiar with Cologuard, so that is a test for colon cancer, and GRAIL test, that's a test for 50 different cancers.

Both of those are blood tests, right? Cologuard and GRAIL?

So Cologuard is, is actually a stool test, but, but, um, but, but GRAIL is a blood test. And so to talk about GRAIL, because it's a good analogy for the Harvard study, when you get pancreatic cancer, lung cancer, prostate cancer, colon cancer, you start expressing your genes differently. And so if you just take a small blood sample, you can, you can find that epigenetic fingerprint for those different cancers. And so that's why with a few drops of blood they can diagnose all of these 50 cancers. So the Harvard study, they were asking, well, why can't we find the epigenetic fingerprint of every other chronic disease— cardiovascular disease, COPD, the things that uh, killing us the most, Alzheimer's and dementia. And they had incredible results with that. Now, what people normally think of epigenetics is you also can tell biologic age, pace of aging. That's what people normally think of. But really, when you're measuring genetic expression, it's just much richer information. What I've become convinced of is what we can predict with epigenetics is limited by our imagination and the size of the data set. So I told Mike, when I saw this data from Harvard, I was like We've been wasting our time in genetics. It's epigenetics. That's where you get all the predictive power, and that's why we moved over to True Diagnostic.

Ben Greenfield: So is there an example of like something that just a basic blood test that people might be familiar with would show you that you could get tested via an epigenetic test also, but it would say something different? Like, are there, I don't know, genes that are expressed that are related to vitamin D that you could test But then you could also test vitamin D in your blood, you know what I'm saying? Like, like what the difference would be.

So to, to talk about that Harvard test specifically, because it answered that question, so I'm going to back up and go a step at a time so listeners are getting this. Biologic age and pace of aging, we test that with TrueAge, and we can talk about those, but let's set those aside for a second because most people are familiar with those. In this Harvard study, they were saying, can we diagnose cardiovascular disease, COPD, these things? But they also ask another question. They said, can we also predict other biomarkers? So to your question about things like vitamin D, those things, there was a researcher named Richard Marioni who several years ago, he found that you could, with epigenetics, predict CRP and hemoglobin A1C. Now his obvious question when he found these two, that you could predict these two, was, well, how good do they perform? So how, how good is this CRP compared to a LabCorp or Quest CRP? Well, then you have to answer the question, what makes a biomarker good?

How good is a prediction versus a direct measurement?

That's exactly right. So the reason you order a CRP or, or any lab test is to be able to predict disease. Does someone have disease and are they going to develop it? And so that is measured by hazard ratio and odds ratio. And so he looked at how predictive is his epigenetic CRP measure of inflammation versus the traditional CRP. And he actually found it was more predictive for cognitive decline and these other things. So it was actually kind of an upgraded measure of inflammation because it wasn't just measuring CRP, it was measuring the epigenetic effect of inflammation. So in the Harvard study, we had hypothesis, we thought it'd be really cool if we could find another dozen or two dozen of these upgraded biomarkers, biomarkers that predict something like vitamin D or inflammation, CRP, hemoglobin A1C,, but are better predictors at what you care about, which is the disease progression. And we found 1,600 biomarkers we could predict. When we measured them against their traditional versions, about two-thirds performed better. So better hazard ratio or odds ratio. So we found about 1,000 quote-unquote upgraded biomarkers, and that's how we developed the True Health Test. It's about— it's the top 100 or so of the ones that actually are better at predicting disease. Than the traditional LabCorp or Quest versions of those biomarkers.

Ben Greenfield: Okay. So, if I'm getting a True Health test, I mean, I got one, I have my results pulled up somewhere here, and there's a lot of different data points, more than I might see on an average blood panel that I might get from the doctor. But are you saying that a lot of these biomarkers, like I'm just scrolling through everything from stress biomarkers to mitochondrial biomarkers to vitamins, et cetera, that these were all like my levels of these were predicted, not directly measured, or were some of them directly measured and used to predict others?

That's right. So they were not directly measured, they were predicted. Now, that prediction, when the only ones that are included in True Health are ones that are then better at predicting disease. So I'll give you an example: hemoglobin A1C. So all hemoglobin A1c measures is, is glycolated, uh, hemoglobin that correlates to glucose, which correlates to microvascular damage, which correlates to stroke and heart attack. So that A1c is a correlate for heart attack and stroke. Well, our A1c measurement isn't directly measuring A1c, but is a better predictor of the metabolic outcomes. So if I have a hemoglobin A1c that I got from LabCorp Quest or this version, they're not going to be exactly the same, but I know that the hazard ratio and odds ratio, the prediction of disease, is better with the epigenetic version. We only included ones that had better hazard ratio or odds ratios.

And it is predicting my hemoglobin A1c based on certain genes that are being expressed?

That's right, yeah. So yeah, so we looked at— yeah, that's exactly right.

Okay.

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And then the prediction, obviously you need data to make a prediction. So, is the predictive data just basically from like a large pool of individuals who have had both blood markers and gene expression tested and outcomes.

Yeah. So Harvard has 100,000 patient biobank, and then we also have access to Generation Scotland, which is 18,000 patients with epigenetics and outcomes. And so we train on that massive dataset then. So now when we take your blood, we look at about a million sites, how much each gene is expressed, and then from that we can give that here is your metabolic health number. It's not actually A1C, it is a more predictive version of that. Got it.

And I'll embed my own results in the show notes if anybody wants to actually see what results look like. Those will be at bengreenfieldlife.com/trupodcast, T-R-U, True Podcast. It was a combo test that you sent me so that we could kind of look at it leading up to this podcast. It was a TrueAge test and a True Health Test. You just got done describing kind of like what the True Health Test does, but what's it actually doing that the True Age Test doesn't? Because the True Age Test does give you your pace of aging and I think even like your risk of certain diseases, doesn't it?

Yeah. So, to talk about True Age for just a second, there are hundreds of "biological age tests" out there. And what does that even mean? What is your biologic age? Uh, so not, not to get too simplistic with your listeners, but I think this is important because there's a lot of confusion around it. We know age is the number one risk factor for disease, um, and mortality, uh, period. But we all know that a 45-year-old— we've seen 45-year-olds that look and perform like a 35-year-old, and those looking for them like a 55-year-old. So we know there's something other than chronological age, and that's what, that's what we're talking about when we say biologic age. There's no formal definition of biologic age, but when I talk about biologic age, I'm talking about a global number that tells me your risk of dying and getting sick. That's what biologic age is to me. We have over 1,000 algorithms that we have, uh, rights to. We only report on 3 biologic age tests. Developed by Harvard, Duke, and Yale. So in your report, you got your OMIC-MH. So that's a Harvard algorithm, and it's been published in Nature Aging, and it is the best one at predicting your mortality over the next 10 years, the likelihood of that, that you're going to die. Then you have the Dunedin PACE. That is my favorite of the biologic age tests. It's developed by Duke. And it has actually been shown to be the best predictor of morbidity and mortality, period. There was a really big trial called the BASE-2 trial that just came out in the last month, and it is better than grip strength, VO2 max, all the other things. It was shown to have a better predictive power. And I want to know that— what is someone's risk of mortality and morbidity? And the last one that we report on is Symphony Age. It's developed by Yale, and the great thing about it is it that while OmicAge tells you that kind of global biologic age number, PACE tells you your pace of aging. It's more like your speedometer. So if OmicAge was your odometer, how many miles, PACE would be your speedometer. And then SymphonyAge tells you different organ systems, because we age in a heterogeneous way. Your brain may age faster than your liver, than your kidneys. So that then kind of tells you why you'd be aging faster or slower, like what is the weakest link in the chain with the organs. So they tell you 3 very different things. You may ask this question, but I will say one thing important to talk about is what makes a good biologic age test or not and why we chose those 3. I don't want to— I want to let you lead, but I think there's so much confusion in the field that that would be something important to talk about.

Yeah. I'd be curious about that. It is interesting. I have my results pulled up right now. And again, if people want to look at them, you can. I'm an open book as you all know. My heart my immune system and my kidneys on that Symphony age, those are the ones that seem to be aging faster. So, you can get a little bit more precise here with the organ systems. Looks like my hormones are aging slowly, liver aging slowly, metabolism and musculoskeletal, those are the healthier values on the Symphony test. So, those are like some of the organ systems that you can look at. My Dunedin test, like the pace of aging, is 0.7. Below 1 is good. That means every year that passes, my body is aging biologically 0.7 years. But then, the Ohmic M, I think it's just a load of hooey, that test, because it says I'm 47. It's lying. It has to be. No, I'm just kidding. I would not be surprised if that could be my Ohmic M age, the one that was developed with Harvard, the deeper reflection of biological age. Part of that might be due to, speaking of Kilimanjaro, 20 years of masochistic endurance racing for the early phases of my life. But, it is interesting if you compare all 3 of these together and see the pace of aging, the biological age, and then the different aging rates of the different organ systems. So, you had mentioned that there's a certain level of quality or difference when you're looking at a biological test. What do you look for on these? Just to know like what biological test is good.

Yeah. And I will say your tests are actually pretty classic for your life, and they're similar to mine, they're similar to other either hard-charging entrepreneurs or athletes who have done the masochistic stuff like you said.

Yeah. Let's face it, we are not just like gardening and walking, you know, dwarf goats up the side of a mountain to collect water each morning. We are I know you, you're a little bit like me, we do like to go out and pound the pavement.

Yeah. And, at the same time, from what I understand just talking to you, you've tempered that down a little bit at this stage of your career or just your life.

Well, relative to Ironman training, yet anybody who goes with me to the gym typically still gets their soul crushed, but it's definitely less voluminous.

Yeah. And, you're a little smarter about it, you've learned a lot over the years. And, while you may have done some real damage and have that kind of slightly related biologic age test. The one that matters for what's going on right now is the PACE test, and you're aging 30% slower than normal. So what that tells me is, sure, you did some crazy stuff, but now you're like dialed in and you're like pulling it back. But to get back to your question of what makes a good one, so I just had a, um, an hour and a half discussion with Matt Kaeberlein yesterday, and there's been recently things by Matt Kaeberlein and Peter T. and Andrew Huberman talking about biologic age tests in general, and there's skepticism in the field, which is absolutely correct, because what I would say is 90% of the biologic age tests out there are junk. And I'm not going to talk about any other, like, companies or anything in any negative way, but I think it's— there's very— there's 4 criteria that make a good biologic age test, and almost, almost no tests follow this. Number 1, it has to be the test and the results and all the metrics have to be published, the methodology, all of those things. So we, we've published almost 100 studies over the last few years, and these 3 age tests that we're talking about are published in Nature Aging, these big journals by Harvard, Duke, and Yale. So it can't be a black box. You can't say I've got an algorithm, trust me, on biologic age. So that's number 1. Number 2, it has to actually predict outcomes. The reason— if it, if it doesn't, if it's not better at predicting morbidity and mortality than chronological age, then it's useless. If it's— and, and very few tests actually, actually achieve that, actually better at predicting mortality and morbidity, but these three do, and they've been published. The third thing is they have to be reliable. So if you send the same test, two of the same tests the same day, there has to be reliability.

Which you, which you hear a lot about, like these investigative journalists or, you know, YouTubers will actually do that, send in two tests different days, sometimes figure out how to use a different name, get completely different results.

Yep, yep. And that, and there's a very specific metric for that, for that reliability. It's called ICC, or intraclass correlation. I haven't really, I don't think I've seen a published ICC for almost any of the other biologic age tests other than these three. And these 3 are excellent. To just to give you examples of what ICCs are, you think— you take things like lipids, like LDL, HDL, those are usually kind of in the 0.8s as far as ICC. So 1 would be perfect. Most of your lab metrics are between 0.7 and 0.9. VO2 max, grip strength, those are like low 0.9s. The Dunedin Pace OmnicAge and Symphony are all over 0.95. Um, really good technical reliability when you're seeing the same one. So have to, have to be reliable. You have to know if you— when you get a different result, it's actually different, or is it just random noise in the system. Yeah. And the last thing is, um, these tests have to respond to interventions. Like, as a clinician, I'm sending them because I want the predictor of, of outcomes like your morbidity, mortality. It's got to be reliable. And then I want to be able to do interventions and see how it changes over time. So those are the 4 things that really have to be true to make a biologic age test good. And when I hear people talk about biologic age tests quote unquote not being valid, I shake my head. Yes, 90% aren't. And these 3, the reason we report on these 3 is because they nail this, they, they nail those 4 things, and they're the ones that are reliable and meet these criteria.

Ben Greenfield: Yeah.

With the True Health test, it is a little bit of a leap of faith, isn't it? Because you'd be tempted to do the test but then maybe do a separate blood test to check and see how accurate all this data is. But again, what you're saying is it's based on such big sets of population data that you guys have already accounted for that. You can literally do the True Health test and just know that with pretty good confidence those levels are going to be close to what's in your blood, and perhaps more importantly, close to what's actually reflective of potential disease.

That last part is the real one. Yeah, because I'll do both. I will send regular lab tests and the True Health, and they don't always match up. And so if I get a hemoglobin A1C is one place and I get the True Health in the other They're measuring slightly different things. HbA1c is directly measuring glycated hemoglobin. The True Health version is measuring the effect of that in the body. So if I feed both of those into an AI engine, I'm actually going to give higher weight to the one that is actually predictive of disease, uh, for me, because there's other factors that go into that. So they won't match perfectly, but again, the only ones we report on are ones that have better hazard ratio and odds ratio for disease, which is what we really care about.

Yeah. And back to what I think you named as the fourth criteria, this idea of responding to intervention. Has that actually been studied much? Like, when I look at this data, if I were to act on it and implement some of the— I mean, you got supplement, lifestyle. I don't recall if there were exercise recommendations on there or not, but are there actual interventional trials showing that acting on this data actually works in some meaningful way?

Yeah, so that's a great question. It's an important question to ask for any epigenetic test. So, um, there are a ton of intervention— conventional studies for the biologic age ones to report on, specifically Dunedin PACE. So there was the CALORIE trial. So this is a randomized control trial, 2 years caloric restriction, Dunedin PACE. All the things you would think would improve with caloric restriction— your lipids, blood pressure, glucose, inflammation, weight improved, as did the DunedinPACE. So it was proven, like, okay, yeah, this responds to interventions. The REPRIEVE study— this was looking at pitavastatin and HIV. Uh, the SLIM LIVER study— this is semaglutide study. There's several others. So we know DunedinPACE and these biologic age tests, they do— the ones we report on— respond to intervention. Now, the, the EBP, the, the true health, these biomarkers Those are— are multiple universities are studying those. There's no published data yet on those responding, so I like to only talk about published data when we can. But Yale, Generation Scotland, like multiple other universities are validating those as well. Right now all the validation we have is internal. We validate it in multiple different cohorts. There's a lot of interventional trials showing you do the right things and these actually respond. So, you can follow them over time and kind of optimize your health with them.

Ben Greenfield: Yeah, I've got my TrueAge test pulled up right now. And towards the end of the test, it gives recommended interventions and testing. Just lightning round, there's spermidine, there's NMN or NR for boosting NAD levels, there's quercetin or other senolytics, right, to clear senescent cells, there's vitamin D3 and K2 for immune system, Mediterranean diet, polyphenol-rich foods, cruciferous vegetables, adequate protein intake, prebiotics, and fermented foods. And then, as you were just talking about, caloric restriction, strength training, high-intensity interval training, hyperbaric therapy, prioritizing high-quality sleep, and then goal setting, journaling, dietary modification, sleep hygiene, avoiding harmful habits, and stress management. Now, those are all listed on my test. I'm assuming those are like generic and those are going to appear on anyone's results because you've looked into those as actually being the research-proven methods that would change biological age in a positive way?

So, they're not completely generic. So, most of those are things that we just know in general do. And a lot of those are driven by the advanced TruAge test where you see the epigenetic biomarker proxies. So, if there are certain things that are off, then it'll reflex to giving those recommendations. But yeah, most of those are things that we just know in general improve biologic age based on those interventional studies that we, that we talked about.

Okay, when you said the advanced, I guess I do have another report here. What's, what's the advanced TruAge test showing me that the other one isn't?

Well, everyone's getting it. Is that— that part is just— so in the Harvard study where we, where we came up with omic mAge, and again, that was just published in Nature Aging in the last few months, They were looking at these epigenetic biomarker proxies for why are you aging faster or slower. And so we report on a lot of those as well, and that helps give a little more personalized guidance to the recommendations, not just decrease your stress, sleep better, those things. So a lot of the recommendations are things we know will help everyone, but some of them are more related to, for example, if you had more stress markers in the EBPs, then there may be more of an emphasis on stress reduction than other people would get.

Okay, I got it.

I might have to take a deeper dive into that advanced report because I didn't realize it was getting more personalized. So, it's the same test, you get two reports, you get your basic overview TrueAge report and then you get your more advanced deep dive.

That's right.

Okay. And, that's still separate from the True Health report.

Yeah. And, the test you got, it was one finger stick, a few drops of blood,. And we can run both the TrueAge and the True Health. That's what most people get when they order the test. And so you can just get one, but they just go together so well. It's like how my global marker, my pace of aging, that correlates most over any other biomarker with morbidity, mortality, based on the BASE-2 trial— I'm saying that with evidence— and then why, like, what are all the biomarkers that I need to improve? So they just go together, the big picture and then the why, what can I actually do about it.

And this BASE-2 trial pretty new, isn't it?

It's brand new. And that's why, like, it's— for me, when I hear— I mean, I— when I hear sometimes, uh, some of the influencers and things talk about biologic age tests, a lot of times they're talking about old literature and they're talking about past tests. And I don't necessarily blame them, but it's— it's all the really good data has been in the last year or so. Base 2 was just in March, in the last 30 days. And it really is the nail in the coffin for anyone that says biologic age testing isn't ready for prime time. I mean, what they, what they did, they looked at over 1,000 adults, like multi-year follow-up between 4 years and 10 years, and they looked at the 14 kind of consensus biomarkers that we know are really good, or we've thought are really good at predicting mortality. So things that everybody talks about— grip strength, IL-6 inflammatory stuff, standing balance, cognitive health, VO2 max, muscle mass, all the IGF-1, all these big things. And they ranked those 14. What are the strongest predictors of mortality? Dunedin PACE was the number one. It was above all of these other ones.

Yeah, and then that's just the very simple pace of aging, like 0 to above 1. Like the clock.

That's right, the one that you got 0.7 on, which is phenomenal. That means you're aging 30% slower. So when I see that and I see your entire, like, test, I'm like, all right, number one, Ben is crushing it. He's got this 0.7 pace. That's phenomenal. Great. Now I can look and say, how— what can we dial in? What can we improve? What are other things? But that is just like the number. If there was one global marker of health for me, it's a Dunedin pace. And I base that— I've said that for a while, and I, and I've referred to certain certain studies, certain reasons why. And when I saw the BASE trial come out last month, I was like, all right, great, this is the real study that, that answers that better than any other. And I feel, I feel much better in my belief. My belief is more science now and less belief.

Yeah, back to your Kilimanjaro training trickery. It seems to me like there's potential. I don't know if you guys are working on this, I don't think we've talked about it. At least if you are, it seems to me like there's potential to take, let's say, each of those epigenetic biomarkers on something like a True Health Test and track certain interventions and see how they individually respond above and beyond the global raising or lowering of the Dunedin pace, couldn't you theoretically using an LLM actually track, you know, whatever, I'm taking spermidine, I'm taking NAD, I maybe you know, increased my HIIT training, lowered my zone 2, what markers were affected?

Absolutely. So, and that's the beauty of True Health. So before True Health, what I— the way I use like the Dunedin Pace is, okay, Ben wants to do an experiment, wants to do IV stem cells in Panama, or he just wants to start spermidine supplementation, for example. Well, I want something, an objective marker of is it working. So I would use Dunedin Pace because I look at it as the biggest global one, because I couldn't really measure your spermidine at the time. I couldn't really measure effects of stem cells so well. So I'd use that global one. The problem with that is if you started spermidine, it's not— you know, every— we all know it's not a perfect experiment. You may or may not sleep better or worse for those 2 months. You may or may not eat differently, your travel schedule. It's not a perfect experiment. And so it's hard for— to see a change in something like Dunedin Pace from one supplement. So that's difficult to isolate those variables. But with True Health, okay, great, now we're actually measuring your, your epigenetic proxy for spermidine. So it's, it's a little easier to do these one-off experiments when you have more granular data. And that's exactly what I did. So in my AI training, I would upload my True Health, and that was what would guide kind of my supplementation stack to, um, your vitamin D, your omega-3, your— are you going to do spermidine, are you going to do vitamin C? All of these things, I would have it help guide the supplements more by having the more granular data.

Have you ever thought about the potential for a platform where people are actually granting access to their information, uploading their protocols, and you're basically collecting enough big data over time to say, "Okay, we have found that the," let's say maybe the number one thing that affects something like hemoglobin A1c or the top 5 things are these 5 parameters that we can predict with pretty good accuracy across a wide range of individuals is going to be effective at modulating that value.

Sure. So there's a few ways to do that. We've done it some, and we're going to do it more. So most of our, our studies we've done with, with Harvard or Generation Scotland. And in Harvard, when we pull, let's say, 10,000 patients from their biobank, we also get all the medical records, all that data, granular data, so we can do predictive things. Now, when people just do our test, they have the option for opting in to research. And if they do that, there's also a questionnaire of what are you taking, what medications you're taking, what supplements you're taking. And so we're collecting that data as well. And, if people opt into that, then we absolutely can create more and better recommendations.

Ben Greenfield: Now, you're jogging my memory. I've done, what, I've probably done 4 tests, I think, through True Diagnostics. And, I know the test landscape is evolving and what you're testing for is evolving, but I think every single one, I answered a pretty comprehensive questionnaire. So, that questionnaire is not just for mere curiosity for my own purposes, you can use that data to develop more precise recommendations over time.

Yeah, that's exactly right. We, we have the largest data set, private data set of DNA methylation epigenetic tests in the world. We have over 100,000, so we can do this, this science and create better predictors. Now, when we release kind of the, the AI version that's in beta now, answering those questions will actually help give better recommendations for you. So far, they've just been— answering these questions have been great. Now we're going to be able to give you better information on your next tests because we'll feed it into the to the AI engine. And some people, you also can opt out. It's either an opt-in or opt-out to letting that be studied. We respect people's decisions there.

Ben Greenfield: Right. You don't have to tell people whether you're sleeping in boxers or briefs. You can keep that to yourself. So, based on what you do know, I mean, I want to get into some brass tacks because this is interesting so far. I just listed off a little while ago a whole bunch of somewhat proven tactics for slowing aging or addressing these biomarkers. But on your end, you've mentioned spermidine a couple of times. What are some tactics that just in the experience you have so far with your own data, seeing a lot of other individuals' data, what really moves the dial? Like, what are the things that maybe are lesser known or underrated or you just know globally are going to have a really good impact for people on aging?

So, I'll name the big ones that are published now, name the ones that just is kind of internal data and we've seen. I mentioned some. I mean, we know caloric restriction, that does increase longevity in most mammals.

Caloric restriction, is there a— I know there's a difference between, say, like alternate-day fasting, intermittent fasting, fasting-mimicking diet in terms of certain diets having greater potential to, say, preserve lean muscle mass through calorie restriction. But what I'm curious about is have you seen or come across anything that would show the impact of calorie restriction if it's done via, let's say, uh, just steely willpower versus calorie restriction accomplished through the use of a GLP agonist?

No, that's not been studied directly. And we have actually done studies with both Novo Nordisk and Eli Lilly on semaglutide and and terzepatide. And, and interestingly, both of those compounds, those GLP-1s, have other kind of longevity effects too. Some have been published now, um, and they get a lot of press, and that— those, those were our studies we did analyzing that data. Others haven't been published yet, but what I'll tell you is those are two very different— like, we see it in caloric restriction, we also see it in the GLP-1s. They seem to be two different things and additive.

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Caloric restriction. Now, having said all that, one of the things about— like, no tool gives you the entire picture. So just because you're done eating PACE and your pace of aging goes down with culture, it doesn't mean more of it is better. You and I know how important muscle mass is. So you could have an incredibly low Dunedin pace, pace of aging, great biologic age, and then you fall and get a hip fracture. You have no muscle mass.

Exactly. You fall off your bicycle and you die.

Exactly. So just, you got to be smart about this stuff and know that everything is a piece of the puzzle. It's not the entire puzzle.

Yeah. All right, so calorie restriction.

Calorie restriction. The couple things that have been studied, and then I'll get into what we've just seen. I mentioned the pitavastatin and HIV. That was great, but I mean, I don't know how many of your, your listeners have HIV, so I don't know how applicable it is to them. There's been some supplement studies. There was the DO Health study, and what they showed is omega-3, vitamin D, and exercise, um, all had good effects. Those were kind of basic things. Now, what they didn't do is separate out people who had good levels of baseline versus not.. But when you looked at the population, those vitamin D, omega-3, like those are ones that people take, and they had, they had effects. There also was a really cool study of preschool children where these kids had some, some psychosocial issues, and they gave the parents training in how to approach them. And the parents that got training versus not, the controls versus— they actually had reductions in, in rate of aging for these kids. So there's social factors we know make a difference. And the other things you would expect, uh, like sleep, optimizing your stress, which has to do with the social things. An interesting one that there's not, not published out on this yet, but we've just seen it anecdotally, that I mean, I just today I had a fair amount of exogenous ketones. Like when we've seen— I don't have like good big studies on this, but it's pretty reliable when I've seen people do studies on themselves of, I am going to increase my ketone levels, even if it's not fasting, it's through exogenous ketones. We'll see interesting effects on pace of aging. And I wish someone would do a bigger study on that because it's— the magnitude has been interesting.

That would be interesting. It's kind of similar to the calorie restriction with the GLP agonist versus without. It sounds like there's, there's different effects of both and they could be combinatorial. It'd be interesting to see, okay, so maintaining high blood levels of ketones, not via carbohydrate and calorie restriction, just via exogenous ketones, if there's a clear winner or if those also are combinatorial. Yeah, it would be.

Now, the fact that caloric restriction, a big study showed it worked. I— and obviously in that caloric restriction, they may have had raised ketone levels. Who knows what their diet was? But just exogenous ketones without really changing your caloric intake seems to make a difference as, as well. But there's not a big study on that yet.

Yeah. What about, um, some of the common biohacks that are popular now? I know hyperbaric is one that's mentioned. On the report, but then there's photobiomodulation, there's cryotherapy, there's, you know, certain electrical modalities like PMF or tDCS. Anything evolving on those as far as like any insight or potential clues?

The tough thing is, so hyperbarics, there was a study several years ago that showed some, some reduction in biological age. The other ones, there's not any big trials. We love doing research, so if any of those companies that have. The problem is who funds these trials, that none of them are cheap. So we— any of those companies that are doing those things, we would love to study it. Um, but there haven't been big trials. Actually, I'll give you one really interesting one. I just got an email today. Uh, we were doing a study with someone who, who was looking at ayahuasca. So this was fascinating. It's not published yet, so I'm not sure how much I'm supposed to talk about it, but, but, uh, we'll still analyze the data. But what it looked like like initially is the fast— most fascinating thing is a lot of the genes that were— became hypomethylated post-ayahuasca were genes related to neuroplasticity. And people talk about that neuroplastic window, and those genes actually turned on, which was a fascinating outcome. We still have to analyze like biological age, pace of aging, But it's interesting when you see— when you hear about subjectively, and you'll hear people talk about things like neuroplasticity, post-psychedelics, and then when you see the science of the specific genes being turned on or off related to that, um, right after the experience. So there's more and more studies on all of these biohacks, whether it's the traditional things you said or even something like that. And the cool thing about epigenetics is not only can you see does it increase or decrease biological age or pace of aging, when you get really granular you can start to see why. Oh, it turned on these neuroplastic genes, for example.

Ben Greenfield: Yeah. The window of neuroplasticity from what I understand is highest for ibogaine. I mean, I think it's like 90 to 120 days versus say, I think a few days for something like ketamine. And of course, I think many listeners have probably already started to hear and see stories on podcasts like Joe Rogan or I think Jillian Michaels had one on some pretty profound neurological changes that occur with that treatment.

Yeah. Well, even this, even this one, we're just looking at the preliminary data, BDNF. So, so genes that express BDNF were actually turned up too. And that's one of the things with also with ketamine we see in some other of these, of these, uh, of these chemicals.

Yeah, like Miracle-Gro for the brain. Uh, let's say that I were I were somewhat reckless and masochistic and wanted to speed up that Dunedin pacing clock a little bit, what would be my strategy? What would be your recommendations to someone as far as the top things that are going to make you age faster?

Yeah, we could do it all at once. What I'd say is stay up all night and don't sleep. And, while you're up, smoke as much as you can smoke, be as stressed out as you can be, and then just overeat. Those are the biggest things. It's excess calories, lack of sleep, sleep, stress, and then the things that we know like smoking and excess alcohol. Those are the big ones that everybody knows about.

So, basically, go to college to age faster.

Yeah, exactly.

Yeah. What about anything related to more psychosocial dynamics, relationships, et cetera? I mean, you know about Harvard's longevity study that was 80+ years long showing that when isolating for a lot of confounding variables, relationship quality, seemed to trump everything.

That's right. It was by far the big— bigger than, bigger than smoking versus not smoking, bigger than, than everything. Um, so again, because the studies, uh, are expensive to fund, there's not been a ton on psychosocial, but there's some, like the one that I mentioned around kids and, and parents just getting good, better parenting skills. So we know that exists. And what I would say about that is I wish more people would do those studies. But all of these studies on like the pace of aging and biologic age, we're looking— those are surrogate markers, they're really good surrogate markers. The fact that this Harvard study on healthy aging was 80 years and 1,000 people, it is the definitive. So I, in my mind, we don't need studies on biologic aging, pace of aging, to know that the number one intervention over everything I'll ever tell you about, oh, they studied this supplement, they studied this medication, none of that is close to the strength of your social relationships. And I think that study was so definitive on that, that anyone who's biohacking and, and not focusing on that, they're wasting their time with, with everything else. That is the biggest thing, is the strength of those social relationships.

Yeah. How many markers total are on this True Health Test? Because I'm actually scrolling through my results right now, which again, I'll put in the show notes for people to take a look at. It's a lot. I'm still scrolling and scrolling and scrolling. I'm seeing a lot of green, which is good. There's a few reds that pop up. Looks like histidine, ApoE, dimethylarginine, a few cardiovascular markers. But, how many markers are you testing and are there markers that are added on a regular basis?

We will add as we feel really good that the markers have been validated. Right now, it's about 100. We have about 1,000 that we think perform better than regular biomarkers. We just like to validate them. It brings up an interesting point and something important to note. I'll give you an example of how to use this. So before we actually even rolled this out to the public, uh, you met Mike, Mike Mallon. He, as he was developing this, he was having a really difficult issue with, um, he has familial hypercholesterolemia through the roof and even like a little bit of, uh, some issues on, on, I could clearly scan and stuff. And so he's taking it, he was taking some medications for that. He's having some insomnia for a year trying to figure out this, this loop around insomnia, these cholesterol medications, trying to get it dialed in. Couldn't get it really figured out. And when we got his True Health Report back, and these 100 biomarkers, it's a lot for anyone to digest. It's too much for a human brain. So we put it into an AI system with, hey, having trouble with insomnia, here's the medications taken, and in seconds it was able to ingest all of that data and tell him, okay, it looks like the medications you're on are causing issues with methylation. It guessed he was a vegetarian, which he was, and basically was like, your medication and your vegetarianism are causing issues with taurine, riboflavin, betaine. All you got to do is eat some meat, bro, or take a few supplements. And he started doing that and he got better. And we actually weren't able to piece that together just looking at all the biomarkers ourselves. So it brings up an, an issue like, one, you get so much information, which is great. But it also— thankfully, we're living in a time where LLMs can actually parse this and give us really good information. That's why we're, we're building the product we're going to be releasing soon that actually has it built in. So anyone that's actually getting this test, honestly, one of the recommendations I make— and there's all, all kinds of privacy issues and other issues for people to consider— but I get a tremendous amount of benefit by uploading these to the correct LLMs and getting information. I mean, as I mentioned, my AI trainer, I was doing that. I was uploading these biomarkers to it.

Yeah, but you're a physician and you probably have a little bit better grasp of the prompts to use. What you're saying is that for people who might not be totally sure of how to query, that you, you are in the process of developing something that will make that a little bit easier for people to upload and analyze.

That's right. And initially That'll be a tool that our physicians use. People can order these tests just on their own. They also can order them through their physician. And, and I always recommend, even though I love enabling people and empowering people to take control of their, their own health, this is a lot of information. So someone does have a physician that orders it and can help them interpret it, that's great. We're initially going to be giving the AI tool to the physicians as well. Main reason is there's just regulatory things around AI practicing medicine. So like, it— yeah, people can get it either way, on their own or through the physician, but I generally like to steer people towards, hey, do this. And if your doctor's not ordering them, they can, um, they can get this for you if they just were to go to our website as well.

Yeah, I, I feel like most of my results look pretty good, but there were a few— I mean, freaked me out. Neurogranin. Haven't I— I haven't really been studied up on. That's a memory health protein, calmodulin-binding protein, that says linked to synaptic plasticity and cognition. High levels are linked to neurodegenerative diseases. And, I have off the charts like 98th percentile, but then underneath that, and this is helpful, it says avoid overtraining, stress management, adequate sleep, L-theanine, magnesium, ashwagandha, phosphatidylserine, and Bacopa monnieri. So, there's kind of a clue already embedded in the existing PDF report about action steps you could take.

Yeah, and for this cognitive one, honestly, I listened to your last few podcasts and I was going to bring up issues with cognition just from listening to them anyway. So I think this, this matches for you.

I sounded that stupid, huh? You know, it's my job sometimes on a podcast to be the dumbest person in the room. Uh, and the look on your face where you thought I was serious for a second, you had me for about half a second You talked about some of the logistics of being able to go through your doctor versus at home, blood spot test, meaning it's the circle that you drip blood on. I forget, you just do one blood spot test and send that off and that gives you both the TrueAge and the True Health, or do you do two separate blood spots?

No, it's just one. Yeah. And so when we get that and then we separate it out and, and can run the test, um, I will say in looking at your results too, they look— again, the number one was that I need pace, which was which is excellent. And then all the small things. Whenever you test 100 things too, there's fluctuations in the system based on training and everything else. So I never put too much stress on one thing.

Okay. So, so there is an acute effect. Like if I had a, uh, you know, back to the soul-crushing workout thing, like if I'd done something hard that the night before and tested, that could acutely affect data.

Yeah. And when I look at your entire picture, that's what I, that's what I kind of saw is like I said, it looks like on the February test, um, you may or may not have been in an acute phase of overreaching. We do that to grow. I mean, in fact, the, the ayahuasca study that I mentioned, it looked like right after that there was some— it was like a, a worsening of a lot of markers, but then the effect later, at like late, like 3 months later, was actually an improvement. Just like it would— an intense exercise, I mean, you're going to have liver function tests from, from liver acute stress after, and CRP, all these things. But we know then 2 days later, it was a good thing for us. So, it really looked like a picture of just like there was a little bit of designed overreaching or some other stressful thing during that one test. Yeah.

It's so interesting how acute things can affect this. In this case, the February test was after an 18-hour flight back from Munich, Germany testing the next morning after arriving at about 11:30 PM the night before. And then, I had different tests through just a normal blood test through my doctor. I have had a history of elevated liver enzymes, so I thought, "What the heck? I'm going to be lazier than I've ever been for a few years and just basically sit on the couch, hang out with my wife, stretch a little bit, and then go in and test." And, the liver markers were pristine, perfect. And, I think one of the reasons I see these elevated liver enzymes is usually I'm testing the day after I've lifted weights or done a workout.

Yeah, I got labs right after the Kilimanjaro thing and my liver, I was like, "Holy crap." I see this in a patient, I'm having them test for all these things. But yeah, it's good to get that reminder.

Definitely. If you're listening and you have high levels of that kind of stuff, do a washout period like 48, 72 hours of just pure laziness and then go test.

And this is why I'm like, "Hey, if you can do this with a physician, that's great, because not everybody— other people get these tests and they're not into this as much as you or I am, and, and they can get concerned. So yeah, take it with a grain of salt. Make sure you have someone that you can kind of go over this with. I would recommend— again, love empowering people, but there's some nuance to it and how you interpret them.

Yeah. Okay, last question here: combo tests. Uh, most of these, I'm assuming, are not covered by insurance, so So, cash cost for someone to order a TrueAge, TrueHealth, approximately?

So, and I will say one thing about insurance. So, where our company is moving is we are actually coming out, we're going to be more— we actually have some incredible diagnostics and predictors for actual diseases and we're moving down the reimbursement pathway. So, we just got— the AMA just gave us 12 PLA codes. So, we're going down the pathway of getting a lot of our tests reimbursed, not the TrueAge and not the TrueHealth. But like, we have a predictor for dementia of— are you going to get dementia in the next 5 years— that has an AUC of over 0.9. It's over 90% ability to discriminate that, and some other really amazing ones. So we are going down in the future. A lot of our tests that— the new tests that will be coming out, predictive and diagnostic, will hopefully have insurance reimbursement. But biologic age and these True Health, these are cash pay. The prices on them, either one, TruAge or TruHealth alone are $499, together they're $850, but I'm 95% sure that we've got a code for your listeners that is a—

We had one the last time we podcasted, so I know it's in there. So, I'll make sure it winds up in the show notes. And then, frequency of retesting. I mean, the pattern I've kind of been on I think has been approximately quarterly. Is that overdoing it?

I would say there's— it depends on how much you're into this. I also do it quarterly. My, my, uh, chief of staff is a great, uh, reference for this. She would do her every quarter for a year and a half, do her PACE and her True Health, and then she would optimize the True Health. And she got all the way down to, I think, around 0.6 of her PACE by doing that. So you can be really intense and go every quarter. In fact, we have a subscription for every quarter But you don't have to. I think every 6 months or even every year if you're kind of a casual consumer. But if you're a Ben Greenfield crazy optimizer, every quarter is— I would say don't do it more than that. I don't do more than that, but I think that's the top level to do is every quarter.

Gosh, I think, I think that covered everything I wanted to ask about TrueAge and True Health. It's just so cool how, how rapidly this science is evolving. And, for me personally, I find it motivating when I look at my score and see, okay, so this organ system needs a little TLC, this number's looking good. So, it gives you motivation, gives you a little bit of power and control over your health. Matt, thanks for being a 5-peat or 6-peat guest or whatever you are now.

Yeah. Thanks for having me on. I will say I'm really proud of myself for not calling you dad at all. I'm looking at you wearing this dad the entire time. And yeah.

For those of you watching the video version, the most expensive sweatshirt in all the land, BenGreenfieldLife.com. Ben-greenfield.com/tru-podcast, T-R-U podcast, for the show notes, which will be juicy. I'll link to the tests. I'll link to my other podcasts with Matt, which are equally as fascinating. And you can grab all that over on the website. Matt, until next time. Thanks, Ben.

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