Ep. 7: Am I a Ticking Time Bomb? Bio-Age Revealed — with Ryan Smith, Co-Founder of TruDiagnostic

Your driver’s license shows one age — but your body may be aging at a very different rate. In this episode, Dr. Regina Druz sits down with Ryan Smith, co-founder of TruDiagnostic, to unpack the science of biological aging and DNA methylation “clocks” — tests that can estimate how fast you’re really aging from a few drops of blood. They trace the field from Dr. Steve Horvath’s 2013 breakthrough to today’s most predictive tools (DunedinPACE, OMICmAge, and SymphonyAge), and Dr. Druz opens up her own results live — including why her heart and immune “organ ages” ran ahead of the rest. If you’ve ever wondered whether you’re a “ticking time bomb,” this conversation reframes aging as something you can measure — and change.

Watch on YouTube: A video version of this episode is available on the Own Your Heart Health YouTube channel. Subscribe to be notified of new episodes.

Episode Chapters

[00:00] Introduction & Meet Ryan Smith
[01:45] From Med School to Entrepreneur: A Winding Road
[04:15] What Is DNA Methylation?
[10:00] The Horvath Clock & First-Generation Clocks
[12:30] Second-Generation Clocks: From Birthday to Biology
[15:30] Telomeres vs. Methylation Clocks
[20:30] The Newest Clocks: DunedinPACE, OMICmAge & SymphonyAge
[25:30] Dr. Druz’s Own Report: A Top-14% Result
[29:00] SymphonyAge: Aging by Organ System
[35:00] DunedinPACE: Your Pace of Aging Right Now
[41:30] The New Test: Predicting Biomarkers from Methylation
[47:45] What Actually Works: 51 Interventions Studied
[56:00] Closing & Where to Learn More

Transcript

[00:00] Introduction & Meet Ryan Smith

Dr. Regina Druz (00:00): Welcome to Own Your Heart Health. I’m Dr. Regina Druz, your holistic cardiologist. This week we’ll dive into common heart health concerns, uncovering root causes and unpacking scientific discoveries and controversies. The information provided does not constitute medical advice. Please contact your healthcare practitioner before making any changes that may impact your health.

Dr. Regina Druz (00:30): Welcome, everyone. Today I’m excited to have Ryan Smith, co-founder of a groundbreaking company called TruDiagnostic. TruDiagnostic gives us a way to understand biological aging. You have a driver’s license or passport, and whatever age it shows is the age you are — but that’s not entirely true, because your body and your biological systems age at different rates. Some of us are about the same as our license age, some substantially younger, and some, unfortunately, substantially older. This is a rapidly evolving area of research. Ryan, tell us about yourself.

Ryan Smith (01:15): Thanks, Dr. Druz, for having me — I’m happy to be here. I’m the co-founder of TruDiagnostic. We started the company in July of 2020, so it’s a little over four years old now, with the idea that we wanted to quantify aging using a unique technology called DNA methylation. I lead the company and most of the strategic research behind it.

[01:45] From Med School to Entrepreneur: A Winding Road

Dr. Regina Druz (01:45): I just learned moments before we started recording that you aren’t a PhD — you took a different route. Tell us about that.

Ryan Smith (02:00): It was a long and winding road. As an undergrad I always wanted to be in medicine, so I majored in biochemistry and went to the University of Kentucky for medical school. I finished my first two years and passed USMLE Step 1, but when the clinical portion started in the third year, I just didn’t like it. I didn’t feel I was helping so much as following and triaging patients. So I made what looked like a very poor financial decision and quit. A few months later I created a compounding pharmacy called Tailor Made Compounding. We were lucky enough to have real success — the fourth-fastest-growing company in healthcare — going from me as the first employee to over 200 employees in two and a half years. We were doing unique work with peptides and proteins, but a lot of it didn’t have long-term safety or effectiveness data, and I was always looking for ways to validate what we were doing. That coincided with the emerging science of epigenetic clocks, which could predict outcomes like death very accurately. I got so excited about it that I sold that company in early 2020 to create TruDiagnostic.

Dr. Regina Druz (03:45): So the lesson is: when medical students leave, they become groundbreaking entrepreneurs. As an entrepreneur myself, later in life, I can see the advantages and disadvantages. For our listeners — and if you’re listening on your favorite podcast platform, I encourage you to watch this one on YouTube, because I have a little surprise that’s much easier to see than to describe — what are DNA methylation clocks, and how has the science evolved?

[04:15] What Is DNA Methylation?

Ryan Smith (04:15): Before I even get into the clocks, I want to stress the importance of aging itself. People hear “aging” and think of aesthetics — skin, appearance. What most don’t realize is that aging is the biggest risk factor for almost every chronic disease and for death. You can have two people with the same biomarkers at 30 and the same biomarkers at 60, yet very different disease burden and quality of life. If we want real preventive medicine, we have to address that biggest risk factor: the biological aging process. Just increasing lifespan by one year worldwide would save enormous amounts in healthcare spending. We already know chronological and biological age differ — most people know someone in their sixties who looks fifty, and vice versa — because we don’t all age the same. The search for a way to measure this went on for a long time, but in 2013 there was a huge breakthrough from Dr. Steve Horvath at UCLA: a clock that could accurately predict a person’s chronological age from any tissue. That suggested we might finally be able to molecularly measure the process we most want to quantify.

Dr. Regina Druz (06:30): This is so important. At Holistic Heart Centers we often see patients troubled when we find signs of aging in their cardiovascular system. In an earlier episode I talked about the coronary artery calcium score. I always emphasize that you may look great on the outside, have optimal body composition, eat well, and exercise — but it’s the internal measurements of aging that tell the full story. One surrogate marker is the calcium score, or the overall burden of atherosclerotic plaque we can detect in the carotid or heart arteries. We see a clear escalation of coronary calcium in middle age, even in people without symptoms. With Ryan, we’re going much deeper. So let’s define DNA methylation.

Ryan Smith (07:45): Most people know about genetics — the genomic sequence that makes you, you. It’s specific to you, but it’s the same in every cell of your body: your skin, heart, and brain all carry that same DNA. Yet those tissues behave completely differently. How? By which genes are actually turned on and expressed versus turned off. That’s regulated through epigenetics — literally “above the genome.” DNA methylation is one of the most common epigenetic changes, and it’s essentially the off switch for a given gene: the more methylation attached, the less that gene is being transcribed. So we’re reading the off-switches of your DNA — and that’s what surprised everyone in 2013 with how accurately it predicted a person’s age.

Dr. Regina Druz (09:00): Hi everyone, it’s Dr. Regina. I know there are contradictory opinions about nutrition for heart health and longevity — the discussion gets heated and confusing. Some push low-fat, low-cholesterol; others are fans of ketogenic diets; and there are many voices urging vegan or vegetarian eating. To cut through the clutter, my team and I created Holistic Heart University: on-demand courses, nutrition and lifestyle resources, and supplement guidance to make healthy choices for your heart easier to understand. I’m especially proud of our open office hours and the Q&A feature where you can put us in the hot seat. Head to the show notes for the link and use promo code OWNER20 for 20% off our annual subscription. I’ll see you in office hours.

[10:00] The Horvath Clock & First-Generation Clocks

Dr. Regina Druz (10:00): So the Horvath clock was one of those first-generation DNA methylation clocks. It looked at patterns of methyl groups — small molecular tags added at strategic places on a person’s DNA. Epigenetics is fascinating partly because of how we discovered methylation matters: the Agouti mouse experiments. Mice deficient in methylation were overgrown, fat, and short-lived, while mice fed a diet rich in methylation-supporting nutrients were lean, agile, and less prone to early death. So this is an extension of that concept in humans. After Dr. Horvath launched his clock, what happened next?

Ryan Smith (10:45): When Steve first launched it, it wasn’t used as a health tool. It was used for things like forensics — estimating the age of someone who left DNA at a crime scene — and, notably, during the Syrian refugee crisis, where European agencies used it to tell whether refugees were adults or minors, and therefore eligible for asylum. It didn’t become a health tool until it was run in large biobank cohorts, where they saw a striking pattern: people who were biologically younger than their chronological age were protected from negative outcomes, and those who were older were at higher risk for them. That told us the clock wasn’t just capturing chronological age — it was capturing a biological signal predictive of health outcomes, which matches what we know about aging being the biggest risk factor for chronic disease. But there was a problem: the better those clocks got at predicting chronological age, the closer they just got to telling you your birthday.

[12:30] Second-Generation Clocks: From Birthday to Biology

Ryan Smith (12:30): That philosophy needed to change, and it did around 2018, again through Steve’s lab — particularly with a student at the time, Morgan Levine — who trained clocks to biological phenotypes. Instead of just predicting your age, they looked at how your blood-based biomarkers change as you get older and built a clock predictive of that. These are what we call second-generation clocks, and they were even more effective at predicting outcomes than the first generation. That was one of the biggest developments in the field.

Dr. Regina Druz (13:30): Let’s connect this to precision cardiovascular medicine, which is advancing rapidly — the American Heart Association meeting just wrapped up in Chicago with interesting new paradigms. This idea of relating the phenotype, the external characteristics, to what’s happening inside is what we call an endophenotype: “endo” meaning internal, the inside picture versus what we see on the outside. So when researchers looked at databases like the Framingham Heart Study and the UK Biobank, what came out of it?

Ryan Smith (14:15): These clocks could predict risk — and, importantly, associate with patterns of behavior, telling us whether a behavior is helpful or harmful. They became surrogates for measuring the biggest risk and for telling us what reduces it. In the early years they confirmed things that weren’t surprising: exercise generally helps your aging; smoking and drinking are very negative; Mediterranean-style diets are helpful. But now we could quantify how effective each aging strategy actually is — a huge breakthrough.

[15:30] Telomeres vs. Methylation Clocks

Dr. Regina Druz (15:30): Many people interested in health optimization — especially for longevity — used to focus on telomere length. For many middle-aged adults, and even those over 65, longevity is the number-one priority. What is telomere length, and how does it differ from these second-generation biological clocks?

Ryan Smith (16:15): Before we had these clocks, all we could look at was how ordinary biomarkers change over time, and one of the most age-correlated was telomere length. Telomeres are the very ends of our DNA. As our cells replicate — and they’re constantly replicating, so that roughly every seven years we have entirely different cells — we lose a little bit of DNA each time. The body planned for this by capping the ends with telomeres, programmed to be long enough that cells can keep dividing safely.

Dr. Regina Druz (17:30): So it’s our insurance policy — a reserve we draw on as we get older.

Ryan Smith (17:45): Exactly. Because replication is frequent, telomere length correlates strongly with age — there have been over 20,000 studies on telomeres and aging, and the underlying science won a Nobel Prize. But in recent years we’ve found it isn’t the best biomarker of age. It’s highly correlated with age, yet it isn’t very predictive of health outcomes — and we want a test that guides clinical treatment, not one we can’t act on.

Dr. Regina Druz (18:45): That’s crucial, because in science correlation is not causation. My favorite example: satellite imagery of a forest fire shows lots of firefighters and fire trucks in the area, but the trucks didn’t cause the fire — they’re there responding to it. So do these second-generation clocks give us more predictive power, both for what’s happening now and for what we can do to reverse it?

Ryan Smith (19:45): Absolutely. To compare them head-to-head: Riccardo Marioni, using the Generation Scotland cohort, asked how predictive telomere length is of the various phenotypes of aging — it explained only about 2.8% of the variance. Even the first-generation clocks we’ve largely moved on from explained over 28% — more than ten times as much — and the newest clocks explain over 60%. So if we have to choose, we want the test that’s far more predictive. That’s not to say telomere length isn’t worth studying scientifically; it’s just that the clocks are far more clinically useful today.

[20:30] The Newest Clocks: DunedinPACE, OMICmAge & SymphonyAge

Dr. Regina Druz (20:30): Tell us about the current generation of clocks. And if you’re at this point in the podcast, this is where you’ll want to watch the video, because you’ll see my own report — I got it a couple of years ago, and Ryan will probably tell me I should be retesting every three months. Let’s lift the mystery: what are the current-generation clocks, and what do they tell us?

Ryan Smith (21:30): I want to focus on two of the most exciting new types. The first is the third-generation clock — like the second generation, trained to biological phenotypes, but with the algorithms trained in the same individuals across time rather than across many different people at once. By following an individual’s longitudinal journey, we get much clearer signals about aging. That clock is called DunedinPACE, and instead of giving you an age, it gives you a pace of aging — how fast you’re aging right now. It’s more responsive to change, so for short-term interventions it’s one of the most useful, and it’s also strongly correlated with quality of life. People often tell me they don’t just want a long life — they saw a grandparent’s last years and want good health span. The good news is health span and lifespan are correlated; improving one generally improves the other. DunedinPACE is even correlated with facial aging, mental processing speed, and IQ. The second exciting category is the newest version of what we call GenXClocks — generation-explainable clocks — because the early clocks could tell you whether you were aging fast or slow, but not what to do about it.

Dr. Regina Druz (23:15): Exactly — that’s the key question.

Ryan Smith (23:30): Right. If all we know is your pace of aging, most recommendations would be the same for everyone, because what works for aging generally works for everyone. To make it personalized, two clocks came out: SymphonyAge, developed with Yale, and OMICmAge, developed with Harvard. They include not just the clock age but information on how and why you’re aging. SymphonyAge gives the age of 11 different organ systems, so you can see which is aging fastest. OMICmAge predicts blood-based biomarkers with high accuracy to tell you what’s out of range and likely increasing or decreasing your aging.

Dr. Regina Druz (24:15): I have to tell you, when I took this test I was blown away — a little finger-prick, a few drops of blood, and then this profound report. At Holistic Heart Centers we’re now close to 75 patients through the first phase of our Fit Your Genes program, aiming to optimize both cardiovascular and longevity outcomes, and we’re approaching the second phase where we’ll retest. So let’s jump into my report.

[25:30] Dr. Druz’s Own Report: A Top-14% Result

Dr. Regina Druz (25:30): Here’s my report. At the time of testing I was 54, and this was my OMICmAge result. What does it mean?

Ryan Smith (26:00): Generally, relative risk is zero when your biological age equals your chronological age. Go above that and you increase your risk of every negative disease outcome; go below it and you decrease that risk. This is a phenomenal score — something we don’t see often — in the top 14% of people we test. With a score like this, you’re looking at roughly a 35% decreased risk of death compared with others your chronological age. This particular algorithm is also the most predictive of time until death — we can predict it with about 92% accuracy within a five- or ten-year window — so the lower this is, the longer your likely lifespan. First and foremost, you’re in a very good spot.

Dr. Regina Druz (27:15): Explain this for our listeners, because it’s sometimes a hard point to convey in consultation: who was I being compared with?

Ryan Smith (27:30): In this case, the 14% is compared with the Harvard population cohort we built the algorithm with — anyone coming to Mass General Brigham, one of the best hospital systems in the world. That’s an amazing score. I should mention that if you compared against our own TruDiagnostic population, it gets more competitive, because most of our population are people who are already very healthy and actively optimizing.

Dr. Regina Druz (28:15): So I’d do a little worse against your optimized population, but I did well versus the Harvard cohort — am I reading that right?

Ryan Smith (28:30): Correct. And the Harvard population is far more representative of the general public. So you’ve done better than roughly 85–86% of the general population, and you can compare results over time.

[29:00] SymphonyAge: Aging by Organ System

Dr. Regina Druz (29:00): Now let’s talk about SymphonyAge. What does it show?

Ryan Smith (29:15): SymphonyAge, built with Yale, breaks aging down into the ages of each organ system — 11 of them, from lungs to liver to inflammation. Unlike your OMICmAge, here we see just a slight acceleration — barely a year — but we want to know why, so we can drill into the resolution.

Dr. Regina Druz (30:00): Before the “why,” I’ll note recent literature describing threshold ages of accelerated aging — I believe around 45 and 60. For individuals it can differ; you’re not programmed to accelerate exactly at 60 — you might accelerate at 54 or 55. So here’s our chance to drill into the organs and see what’s leading the acceleration.

Ryan Smith (30:30): Exactly — we don’t just want to see the information, we want to act on it, focusing where it makes the most difference. So we look at what’s highest and what’s lowest — where you’re doing well and where you may need more attention.

Dr. Regina Druz (30:45): This surprised me. I expected inflammation, metabolic, and hormones to rise to the top. Instead, what surfaced was musculoskeletal, immune, kidneys, and the heart.

Ryan Smith (31:15): Exactly. Your brain age, hormone age, and blood age were all phenomenal, and even your lung, metabolic, and inflammatory ages were younger — but by far the biggest increases were in the heart and the immune system. So those are where we’d focus first for optimal aging interventions.

Dr. Regina Druz (31:30): This is profound, because in the years since, I’ve noticed certain cardiovascular changes — periods of elevated blood pressure that I’m actively working to reduce, though I’m not hypertensive. And the immune system is powerful at preventing many chronic diseases, including some malignancies and dementia. I should have taken this advice more to heart. How often should someone repeat these clocks — is three months enough if they’re making a focused effort?

Ryan Smith (32:30): I answer that based on what people are trying to do. One great thing here is that it reduces the guesswork and lets us personalize. If you’re changing things rapidly, I’d retest more often. If you’re focusing on known, proven initiatives, once or twice a year is plenty to see your direction and get feedback. But if you’re a dedicated biohacker chasing every optimization, you might test a bit more frequently to see what’s actually working for you.

Dr. Regina Druz (33:30): Hi everyone, it’s Dr. Regina. Many of my colleagues and I are seeing patients arrive with self-ordered blood tests. When this trend started, I thought it would help — who doesn’t want more access to their health data? But too often self-ordered labs lead to more confusion and frustration: patients come in with a pile of results and are no better off. That’s why we created HeartWell Toolkits — a curated collection of at-home blood and genetic markers focused on heart and brain health that gives you the data you need to make informed, actionable decisions. You can order them at the shop on holisticheartcenters.com — the link is in the show notes. Use code TESTING10 for 10% off and free shipping.

Dr. Regina Druz (34:30): In our practice and our Fit Your Genes program, we typically retest once a year, because we want enough time for optimization to take place so we can ask whether the interventions were actionable and produced a favorable outcome, or whether we need to address other areas. Now, you mentioned DunedinPACE — what does that one mean?

[35:00] DunedinPACE: Your Pace of Aging Right Now

Ryan Smith (35:00): This is one of my favorite algorithms, created with Duke. It tells you how fast you’re aging right now, at a single point in time. The other ages encompass your entire life history — even adverse childhood experiences correlate with aging in adulthood — whereas DunedinPACE changes more quickly and is meant to be a snapshot of how you’re doing right now. It’s reported as biological years per chronological year. Your result is 0.99 — you’re aging 0.99 biological years for every chronological year, essentially right at the average. The good news is you’re not above one, because above one dramatically increases risk: roughly a 56% increased risk of death and a 54% increased risk of a chronic disease diagnosis in the next seven years. So we want to keep this below one — that’s a priority.

Dr. Regina Druz (36:15): So it samples your aging rate at this moment, versus SymphonyAge and OMICmAge, which reflect everything that has happened over time — correct?

Ryan Smith (36:30): Correct. Sometimes they differ. I often see this in ER physicians who had poor sleep and nutrition, then moved into integrative and functional medicine and improved their lives. Their overall ages might not be great, but their DunedinPACE starts to drop, because they’re headed in the right direction. So it’s important to know which picture you’re looking at when you judge what’s working.

Dr. Regina Druz (37:15): Based on our discussion, I’m inclined to think OMICmAge and SymphonyAge are best sampled once a year, while DunedinPACE could be sampled after, say, three or six months of lifestyle effort to connect the dots. How much change is actually meaningful? If I retest at 0.98 or 0.97, is that actionable, or do I need to be more like 0.8 to say I’m truly aging more slowly than the clock of time?

Ryan Smith (38:00): Great question. First, a study we did — it was even featured on Netflix — on vegan versus omnivore diets. We took pairs of twins, put one twin on a vegan diet for eight weeks and the other on a standard omnivore American diet, and tracked what happened. The rate of aging decreased significantly on the vegan diet versus the omnivore one — even in eight weeks. As for what counts as a meaningful difference, we answer that with the technical precision of the clocks. People ask how accurate they are. One way to measure that is to run the same sample multiple times and see how much it varies — the test-retest error. For DunedinPACE that’s about 3.5%, so a true biological change would be anything beyond roughly 0.035.

Dr. Regina Druz (39:15): Or maybe double that — closer to 0.07? If the standard deviation is 3.5%, then about two standard deviations in each direction would be the threshold for significance.

Ryan Smith (39:30): Exactly. To be extra careful, four points lower or higher — so if you came back at 0.95, we’d be fairly certain you’d done something genuinely good. We call these interclass correlation values, and historically poor precision was a problem for epigenetic clocks: even Dr. Horvath’s early clock had an absolute error of around four to five years, which makes it hard to know if a change is real within that window. But the newest clocks are incredibly precise — SymphonyAge and OMICmAge, for instance, have less than 2% error across repeat draws.

Dr. Regina Druz (40:30): Fascinating. This has opened a new chapter in how I approach patients at Holistic Heart Centers. We’re very data-driven — we optimize metabolic health and track digital biomarkers like stress, sleep, body composition, heart rate, and blood-pressure curves. Now we can also see how our personalized, structured interventions affect the most important thing: longevity. We hope to see OMICmAge and SymphonyAge moving in a positive direction — because we all want to be a bit like Benjamin Button. Ryan, you have a new test I haven’t tried yet. Tell us about it.

[41:30] The New Test: Predicting Biomarkers from Methylation

Ryan Smith (41:30): We report a lot of things — telomere length, fitness biomarkers, even how much you’ve smoked or drunk across a lifetime, all part of TruAge testing. But the new test is really exciting: it tells you about your micronutrient levels — B vitamins; vitamins A, D, and K; amino acids — plus some other striking things. Many in the aging space know NAD biomarkers; we can quantify a lot of those. We can quantify environmental exposures — PFAS “forever chemicals,” predictors of lead exposure, pesticides like glyphosate — and supplement levels such as alpha-ketoglutarate and creatine. Our cardiovascular panel is especially powerful: ApoB, ApoA, polyunsaturated and monounsaturated fatty-acid percentages, GlycA (glycoprotein acetyls), and a full lipid panel.

Dr. Regina Druz (42:45): I’m excited, because in 2025 this is the upgraded test Holistic Heart Centers will run. From the patient’s side, is it the same finger-stick drop of blood, and are these direct measurements?

Ryan Smith (43:15): Great question — the answer is no. We’re still measuring DNA methylation, but using it to predict all these other outcomes, and that’s the most exciting part. To develop the algorithms, we directly measured the things we’re predicting and also measured methylation, then built and validated the algorithms against data we’d never seen. They’re effective: we see the same associations to disease as the directly measured biomarkers, and we see the expected longitudinal change with interventions. The surprising part is that 64% of the time our methylation-predicted biomarkers were actually better than the classical measured ones. For example, our predicted systolic blood pressure is about twice as predictive of cardiovascular disease as a regular systolic reading. We think that’s because methylation captures a bigger picture — like the difference between a single fasting glucose, which varies a lot, and an HbA1c, which reflects a roughly three-month running average. We’re getting a longer-term, more holistic estimate, which often predicts outcomes better than the classical surrogate.

Dr. Regina Druz (45:45): So for cardiovascular risk — where we run tools like the Pooled Cohort Equations, or the Multi-Ethnic Study of Atherosclerosis (MESA) because our patients have coronary calcium scores, and now the AHA’s newer PREVENT algorithm linking cardiac, metabolic, and renal risk — are methylation patterns better at predicting hard outcomes like nonfatal heart attack, cardiac death, and total mortality?

Ryan Smith (46:15): That’s the beauty of it — it’s cross-disease. Whether it’s coronary artery disease, cardiovascular disease, stroke, or congestive heart failure, ours generally outperform, and not just for heart disease — also COPD and even depression. Across all diseases, 64% of our predicted markers are better; for cardiovascular disease specifically, 92% are better.

Dr. Regina Druz (46:45): I wouldn’t expect any less — it should be 95% or higher, because cardiovascular disease is the most impactful disease of our lifetime. I tell patients: muscle is the currency of aging, but it’s your cardiovascular system that sets the interest rate — so you need to understand what those interest rates are. As we head into the closing stretch, what’s your advice?

[47:45] What Actually Works: 51 Interventions Studied

Dr. Regina Druz (47:45): Starting with the comprehensive test plus blood-based biomarkers, perhaps adding DunedinPACE depending on the length and intensity of the program, and then resampling at the one-year mark — would that be a reasonable pathway?

Ryan Smith (48:15): Absolutely — you summarized it perfectly, doing the more responsive algorithms a bit more frequently based on what behaviors you’re changing. The reason we’re excited is cost and access: getting a calcium score, a cardiac cath, or a CT can be expensive and sometimes invasive, whereas DNA methylation lets us quantify a lot of that risk from a single blood-based sample. One recent study built a methylation risk score for cardiovascular disease with an area under the curve of 94%, using the same data we already collect for biological age. Our vision is to apply these epigenetic signatures to many conditions at low cost and avoid expensive, invasive options where we can.

Dr. Regina Druz (49:30): Could that data set eventually report a cardiac age, given the high correlation? Early in my career I was a cardiac imager — still am at heart, pun intended — and reading echocardiograms I could almost predict the decade of life, because the heart changes shape as we age, with uncoiling of the aorta and subtle shifts. So will there be a cardiac age on the report?

Ryan Smith (50:15): Eventually, yes. Not right now, but by the end of February we’ll have a new report — a methylation risk score that gives your risk of cardiovascular disease, coronary artery disease, and stroke, all with areas under the curve of 0.85 or better, from the same data we use to generate your biological age. We published the underlying data with our Harvard collaborators — the same team behind OMICmAge — because they created such a robust data set that we keep mining it for new insights.

Dr. Regina Druz (51:30): You also recently published, I believe with academic collaborators, on what actually works to improve our aging clocks and our pace of aging. Based on that large body of investigation, what’s genuinely effective?

Ryan Smith (52:00): We published this with Yale, looking at 51 different aging interventions over time to see what was best and worst for aging. One caveat: we used every clock ever published in that analysis, which we wouldn’t do clinically — clinically we’d use only the most predictive clocks. After publication, some people tweeted things like “exercise doesn’t work,” which isn’t the case — we don’t want to over-extrapolate. We found some expected things: exercise and healthier diets like the Mediterranean diet do very well. We also found novel ones — hyperbaric oxygen therapy was strong at reversing aging, and among already-healthy people it was the best intervention, with meaningful reductions in DunedinPACE. In some cases senolytics were effective, targeting the cellular senescence that accumulates with aging.

Dr. Regina Druz (54:00): Did metformin make the cut?

Ryan Smith (54:15): Metformin lit up the board as one of the top interventions — but that was in an HIV-positive population, so you’d expect a bigger effect there. That’s exactly why we say don’t over-interpret: some of these studies are in very healthy people and others in much sicker populations; some are eight-week interventions and others run two years, so you can’t always compare apples to apples. What we did confirm is that these newer clocks are very good at measuring change. With SymphonyAge, the organ-specific results made sense: stop smoking and we saw lung age, heart age, and inflammatory age fall; with kidney transplant or dialysis we saw kidney age improve. Getting clear signals in exactly the systems we’d expect is reassuring.

Dr. Regina Druz (55:30): This is fantastic, because patients constantly ask, “How do I know these interventions will work for me?” Alongside the digital biomarkers and blood markers we routinely sample, we can now see whether interventions are effective on a larger scale — overall pace of aging and even organ aging. That’s the translational opportunity that connects the dots.

[56:00] Closing & Where to Learn More

Dr. Regina Druz (56:00): I learned a ton, and I’m looking forward to getting my new kit — hopefully I’m still in the top 14%. Ryan, thank you so much for being with us. To our listeners: if you want to learn more about this kind of testing and what we offer at Holistic Heart Centers, we have Holistic Heart University, where we regularly discuss these topics, with programs for individuals interested in heart health and optimization as well as for professionals and our patients. The link is in the show notes. Ryan, thank you.

Ryan Smith (56:45): It’s a pleasure — thank you for having me, and I look forward to going over your next results.

Dr. Regina Druz (57:00): To the professionals listening: if you’re thinking of launching a cardiometabolic or integrative cardiology program in your practice, we can help. We help physicians expand into hybrid or concierge services — head to the show notes and click the application link; your intro call is free. Ready to schedule a practice review? Use code DOC10 for 10% off our Practice Power Hour, a 60-minute coaching session. Thank you for tuning in to Own Your Heart Health with Dr. Regina Druz. This podcast is powered by Holistic Heart Centers. If you enjoyed the show, please rate and review us on your favorite platform, and visit holisticheartcenters.com and subscribe to our YouTube channel. See you next week.

Frequently Asked Questions

What is biological age, and how is it different from my actual age?

Your chronological age counts the years since you were born; your biological age estimates how much your body and its systems have actually aged, which can be faster or slower than the calendar. The episode explains that aging is the single biggest risk factor for most chronic diseases, so two people of the same chronological age can carry very different disease risk. Biological age is estimated using “epigenetic clocks” that read DNA methylation patterns — chemical tags that switch genes on and off. Newer clocks don’t just estimate age; they predict health outcomes and can flag which organ systems or biomarkers are driving someone’s aging. Biological age is a research-grade tool that’s increasingly used in preventive and longevity medicine, but it should complement, not replace, standard cardiovascular and metabolic evaluation with your own physician.

How do DNA methylation “clocks” like DunedinPACE, OMICmAge, and SymphonyAge work?

DNA methylation clocks analyze where methyl groups sit on your DNA — the body’s gene on/off switches — and use algorithms to estimate aging. First-generation clocks (such as Dr. Steve Horvath’s 2013 clock) were trained to predict chronological age. Second-generation clocks were trained to biological phenotypes, making them better at predicting outcomes. The newest tools go further: DunedinPACE, developed with Duke, reports your current pace of aging (biological years per chronological year) and is responsive enough to track short-term changes; OMICmAge (with Harvard) predicts blood biomarkers and is highly predictive of time until death; and SymphonyAge (with Yale) breaks aging down across 11 organ systems so you can see which are aging fastest. Most are run from a few drops of blood. As always, results should be interpreted by a qualified clinician alongside your full clinical picture.

How often should I retest my biological age?

In the episode, Ryan Smith suggests matching testing frequency to how aggressively you’re changing your habits. For most people pursuing known, proven strategies, once or twice a year is plenty to see the overall direction and get feedback. DunedinPACE — the pace-of-aging clock — is more responsive to change, so it can be reasonable to sample it after a focused three- to six-month effort, while the broader OMICmAge and SymphonyAge ages are generally best repeated annually. Test precision matters: DunedinPACE has roughly a 3.5% test-retest error, so a genuinely meaningful change is usually a few points beyond that, and Dr. Druz and Ryan discuss using about two standard deviations as a conservative threshold. Dedicated biohackers may test more often. Talk with your physician about what cadence makes sense for your goals.

What actually slows or reverses biological aging?

TruDiagnostic’s study with Yale evaluated 51 aging interventions. The reliable, expected winners were the fundamentals: regular exercise and healthier eating patterns such as the Mediterranean diet, while smoking and heavy drinking accelerate aging. A small twin study even showed a measurable drop in pace of aging after eight weeks on a whole-food vegan diet versus a standard American diet. Some less-expected interventions also showed promise, including hyperbaric oxygen therapy (the strongest among already-healthy people in their data) and, in certain populations, senolytics and metformin — though Ryan cautions strongly against over-interpreting results, because studies differ in population health, duration, and design. The practical takeaway: the basics matter most, and biological-age testing can help you confirm whether your personalized plan is actually working. Always personalize interventions with your own physician, especially if you have existing heart disease.

Show Notes & Resources

Guest: Ryan Smith

Ryan Smith is the co-founder of TruDiagnostic, a CLIA-certified laboratory and health-data company specializing in epigenetic DNA methylation testing. A biochemist by training, he attended medical school and passed USMLE Step 1 before leaving to found Tailor Made Compounding, which became one of the fastest-growing healthcare companies in the United States. He exited that company in 2020 to launch TruDiagnostic, which has since built one of the world’s largest private epigenetic databases and developed widely used biological-age algorithms in collaboration with researchers at Duke, Harvard, Yale, and Stanford. He leads the company’s strategic research and is a frequent speaker on epigenetics, biological aging, and longevity.

TruDiagnostic — epigenetic biological-age testing (TruAge); trudiagnostic.com

Resources Mentioned in This Episode

TruDiagnostic — TruAge epigenetic biological-age testing (trudiagnostic.com)
Dr. Steve Horvath (UCLA) — the 2013 pan-tissue DNA methylation clock that launched the field
DunedinPACE — pace-of-aging clock developed with Duke University
OMICmAge — biomarker-predicting clock developed with Harvard (most predictive of time until death)
SymphonyAge — organ-system aging clock developed with Yale (11 organ systems)
TruDiagnostic / Yale study of 51 aging interventions — what most affects pace of aging
New England Journal of Medicine (2024) — microplastics in arterial plaque (referenced re: cardiovascular aging)
Holistic Heart University — on-demand courses and resources (use code OWNER20 for 20% off annual)
HeartWell Toolkits — at-home heart and brain health lab panels (use code TESTING10 for 10% off and free shipping)
For clinicians: Practice Power Hour coaching with Holistic Heart Centers (use code DOC10 for 10% off)

Holistic Heart Centers

holisticheartcenters.com
HeartWell.ai — AI-powered cardiovascular risk assessment
Address: 55 Bryant Avenue, Suite #6, Roslyn, NY 11576
Phone: 877-511-5166
YouTube: @reginadruzmd
Instagram: @dr.reginadruz
Podcast: Own Your Heart Health — available on Apple Podcasts, Spotify, and all major platforms

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