Aging is often described as a slow loss of options. Less strength. Less energy. Less capacity to recover. Dr. Mark Tarnopolsky offers a more useful lens: the body remains responsive to the signals we give it, especially through muscle.
It's pretty clear to me that almost 10 years after the discovery of the gene that we really had no cures. And what was working for our patients was exercise and nutrition, which I had some practical experience with, but also I had trained in those areas. And we started applying that to our patients that had genetic disorders that either affected muscle and made the muscles weaker. And so the antithesis of muscle atrophy and weakness is hypertrophy that you get with exercise training. And then the big area I was involved in, which was a serendipitous discovery of a patient that had a primary mitochondrial disease within my first few weeks of starting my career. What if a narrative of aging, one of inevitable decline, is fundamentally flawed? For decades, medicine has treated as a condition to be managed, not a process to be reshaped. But our guest, Dr. Mark Tarnopolsky, offers a glimpse into a future worth building, where the relentless march of time is not a sentence, but a dialogue. A renowned physician-scientist at the nexus of genetics, metabolism, and human performance, Dr. Tarnopolsky's work reveals the keys to vitality are not just hidden in complex gene therapies, but are accessible through the power of exercise and nutrition. He stands as a visionary architect of a new paradigm, one where we don't just extend lifespan, but be claimed but reclaim our health span. Prepare to explore how we can rewrite our biological destiny, one cell at a time. Dr. Mark Tarnopolsky is a renowned physician-scientist whose work sits at the powerful nexus of genetics, exercise physiology, and age aging. A trailblazer in neurometabolic and neuromuscular disorders, he leads pioneering research at McMaster University into how lifestyle interventions, particularly
exercise and nutraceuticals, can mitigate genetic disease. More than 500 peer-reviewed publications, an H-index of 140 plus, his impact spans academic, clinical, and entrepreneurial domains. And as the CEO of Exerkine Corporation and Stay Above Nutrition, Dr. Tarnopolsky Tarnopolsky translates research into real-world therapies. Uh his journey from elite endurance athlete to innovator in longevity therapeutics reveals a life lived in pursuit of vitality, resilience, and transformation. And his story perfectly embodies the mission of DNA of Things, that is to illuminate how biology, innovation, and narrative combine to shape and reshape what it means to live well. Dr. Mark Tarnopolsky, welcome to the DNA of Things. Thanks very much. Appreciate being here, and thanks for the invitation. Uh well, your reputation precedes you. We have common friends. Actually, Fadi was the one who introduced us. I think it was a long while back, six six or so months ago. And then we were speaking to Cara recently, uh and you know, she was singing your praises, and uh How long have you been at McMaster University? It's been a good year a long time. I came here as an undergrad in 1979, if you can believe it, after my high school years. And uh left for a brief period of time to do some of my residency training in Rochester, New York. And yeah, work part-time in Thunder Bay when my wife was doing her residency up there, and commuted back and forth. But for the most part, I've been here since' 79. Wow. And when were you officially a faculty at McMaster? I started here as a faculty member. Okay. So, you would have been there when I was visiting and applying. So, that's actually you you started there the year I was born. And yeah, I I actually I checked out McMaster University among
other places in in Toronto, but ended up accept accepting my undergrad offer from House University, and actually did my my PhD there as well. But I was captured by McMaster, and so well, here we go. The the road is led has led me back here. And you know, with good motivation and and enthusiasm, that's for sure, because you know, you touch into an area that I'm I'm quite passionate about. You know, obviously the application of healthy living in a clinical practice is uh you know, I want to say seemingly axiomatic, obviously, yet not easy. Simple, but not easy. And you know, you didn't get there by by, you know, clich or you know, chicken soup. It's you've done a lot of work here to actually prove out the methodology. So, really interested to understand, you know, how you got into this space, because you really started with the well, the mitochondrial medicine. So, how does that kind of evolve? And in particular, I mean, how you've synergized these these, you know, seemingly disparate passions into a single career. So, how did it all begin? Yeah, I guess it really began in high school when I had a really insightful physiology professor who inspired me to go into human physiology. So, I came to Mac in' 79 with the goal to be like him. I wanted to be a physical education teacher. So, I did a combination of biology and physical education for 4 years. And as I was going through, another inspiring person, Duncan MacDougall, who unfortunately passed away recently, who's one of Canada's sort of pioneering physiologist, was my mentor for my fourth-year project. And Wow. uh you know, I started off, if you can believe it, many years ago doing football and downhill skiing. And lost 35 lb when I started running, and realized that I was more of an endurance athlete. So, that's kind of always been there in the background, my interest in sports. And that really matured in my
undergrad, where I discovered endurance sports, and realized that that's kind of where my physiology was. And went to the world championships for ski orienteering. And we were one of the top teams in Ontario in cross-country skiing. And so I wanted to continue to study how exercise could impact human physiology. Went off after that, did medicine. I was hoping then to be a sports medicine doctor. Then got really interested in the research, and came back and did a PhD, partially with Dr. MacDougall and Dr. Setnick and in the nutrition department, where I got interested in nutrition. Then after that, I said, well, you know, to practice, I really need a residency. So, I trained in internal medicine and neurology, and something called physical medicine rehabilitation. And also spent 3 years at night doing extra work in intensive care. So, when I finished, I said, jeez, you know, what am I going to do with my life in terms of my career? So, at the time, my goal was to study and to look after patients who had nerve and muscle disorder. And it was pretty clear at the time that there really were no effective therapies. Everyone was hand-waving when they discovered the gene for Duchenne dystrophy, they'd have a cure in 5 years. But it was pretty clear to me then, you know, almost 10 years after the discovery of the gene that we really had no cures. And what was working for our patients was exercise and nutrition, which you know, I had some practical experience with, but also I had trained in those areas. And we started applying that to our patients that had genetic disorders that either affected muscle and made the muscles weaker. And so sort of the antithesis of muscle atrophy and weakness is hypertrophy that you get with exercise training. And then the big area I was involved in, which was sort of a serendipitous discovery of a patient that had a primary mitochondrial disease within my first few weeks of starting my career. And so mitochondrial dysfunction, these genetic disorders, people have such dramatic impairment that even getting up to get a glass of water is pretty much your VO2 max. And
then on the opposite of that is, you know, what I was involved in, which was endurance exercise, where we have mitochondrial biogenesis and very high VO2 max. So, what I learned in physiology about how we can take a sedentary person and, you know, do weight training and get big muscles and stronger. Take a sedentary person and do endurance training and increase mitochondria and improve VO2 max. We started to apply that to our patients. And it was pretty clear that, you know, sort of the theme in neurology is therapeutic nihilism. We can diagnose, but we can't treat anyone. And you know, through my whole career, I've been trying to pay attention to details of your habitual diet. Are there any supplements that can further enhance the benefits? How can we manipulate these in combination with exercise to either increase strength in those with weakness, like muscular dystrophy, or improve metabolic efficiency if you've got, you know, McArdle's disease, where you can't oxidize carbohydrates, various fat oxidation defects where you can't use fats, or mitochondrial disease where whatever substrate you get have, it just can't be utilized. And we and others have clearly shown that really the most effective therapy for most of these disorders, as is the case with aging, turns out to be exercise and nutrition done properly and studied very carefully to make sure we get the optimal combination with few or to no side effects, or at least mitigate those side effects. Standing up. What about any like autoimmune stuff? Have you done any work there or come across it? Like, for example, like multiple sclerosis. Yeah, so autoimmune disorders that I would be most involved with are the autoimmune muscle disorders. I almost to some extent involved in the nerve disorders, like Guillain-Barr syndrome, when kids come in with Guillain-Barr, which affects the nerves. But most of what we would see would be as dermatomyositis, polymyositis. And we don't know if it's truly an inflammatory disorder, but there is secondary inflammation in something called inclusion body myopathy, which is a sporadic disorder, more common in men than women, but yeah, it is definitely an
age-associated disorder causing inflammation, mitochondrial dysfunction, all the stuff that we all are experiencing as we age. Those five common pathways of inflammation, oxidative stress, mitochondrial dysfunction, impaired protein synthesis, all of those are involved to a large extent in the disorders that we see as they are in aging. And it just depends on, you know, what's the main issue. Do you have a genetic disorder that affects mitochondria? Then you get the secondary effects. Do you have a genetic disorder like a certain form of ALS that affects oxidative stress? Then you get secondary mitochondrial dysfunction. So, you know, at the end of the day, they all kind of converge in a similar fashion at the cellular level. Yeah, interesting to hear you speak really about the two extremes of the population, let's say. I mean, it's death with like rare disease and well, it's physical transcendence in a way with with athletic performance and yeah, and and when you're operating at the the tip of the spear, it's it and you know, the outcome is, you know, very clear. It's it's, you know, world record or, you know, life. It it I think it makes the it makes for effective measurement, right? Like so, I think about, for example, how we know a lot of how we know much of what we know about nutrition, for example, with respect to RDAs, you know, comes from well, men going off to war and being without nutrition and you know, being given survival nutrition with you know, let's just say lower nutrient nutritional density. And so, you know, in the space that you work, it's well, see see, I would call those and and this isn't the right language, but just forgive me. It's like if you had designed an experiment that that way, let's say, it would be an unethical experiment, right? Let's send these guys out with suboptimal food and see what happens in the most stressful conditions, for example.
But, you know, then then it would be irresponsible not to do the perspectival research, certainly. And that was something that I I started to see in, you know, the work that we had done when we worked with athletes previously, predominantly, you know, track track and field athletes, is they're subjecting themselves, you know, to very dangerous things. It's like run as fast as you can, jump as high as you can, right? Jump as far as you can. And they're willing willing to throw caution to the wind and, you know, obviously they have great coaches, but then you you measure success and you also interestingly measure, you know, failure. One of the things that that I saw working with these athletes who had survived long enough in, you know, the high performance world, you know, to to be pre-Olympic or Olympic athletes. And which means they had to survive the training, which is not easy. And what was interesting is that we found 75% of them had injury protective alleles, which if you were to compare to the general population, it would be more like 50 to 25%. So, certainly, there's something going on there in terms of the athlete just being able to survive varsity training. And then, you know, on the flip side, I've been doing, you know, some work with the rare disease community. And what what's interesting there is on rare disease, I mean, it's it's a bit of a misnomer, actually, cuz if you were to put all rare disease into one bucket, it's like well, there's 300 million diagnosed. Okay, well, what about the undiagnosed? Probably close to a billion. And then if you were to throw the carriers into that, it's like probably everybody. Right. So, what I I guess what I'm interested in what I'm getting at there, you know, in so far as the rare disease and how it relates to performance, if I'm thinking about this biologically or evolutionarily speaking, similarly like an athlete, like you get through certain phases of life and development, but then these these mutations pop up. And, you know, the pathology is showing
patterns and the treatments are as it relates to nutrition and exercise, it seems to be some kind of blanket positive impact. But when when you think about, you know, technology, you know, where it was when you started and where we are now, do you see a way, you know, to look at either end of those extremes and I guess understand these mutations better evolutionarily speaking, but then even get more precise and predictive with the clinical application. And And it may be at a certain point where it's like, "Hey, we don't need to go that deep." But that would be an interesting thing to know, too. Yeah, I think, you know, there's a number of ways to look at it. You can either go very reductionist and, you know, really try to take things apart or, you know, you can take a broader approach to it. So, for example, from an athletic performance, people are trying to find, you know, which gene predicts this or predicts that. But, you know, my you know, grade 12 coach in track could look at me and say, "Yeah, no, you are not a sprinter, you are an endurance athlete." But of course, when you're testosterone-filled teenager, you want to do football and downhill skiing, you don't want to do endurance sports. So, there's the flip side. I mean, you can either really get down to it, do muscle biopsies, you know, which you know, my understanding is Eastern East Germany and Russia, you know, were trying to do biopsies on people and put them into specific camps based on your fiber type composition and stuff. But really, you can also take the, you know, hand-waving approach and just have your coach say, "We think you're better at this versus that." And they're usually as good as I think anything that we could do. And so, there's a lot of people thinking that we can now take a look at the gene and say this person has a snip that predicts that they're going to do better. And those are roughly predictive, but at the end of the day, I think we're kind of missing the point. Number one, I think we're missing the scientific point and it's not just your genes, we also have methylation. So, you can have a set of genes and you can mess it up by eating poorly, mess up the
methylation, downregulate or upregulate certain genes just by sticking, you know, a methyl group on that DNA. We also have glycomics. So, different glycosylation patterns can predict, you know, adaptation to exercise. You can even look at glycosylation and methylation and look at somebody's age. You can look at different splicing adaptations. So, there's so many levels that the complexity I think just becomes kind of extreme. So, although I do study basic science and, you know, we look at, you know, monogenetic disorders, which which predict disease and, you know, we find new mutations and we try to prove it at various different cellular techniques to show that there is that disorder. But when it comes to human aging, I think really there's some key points that are broad strokes, I think, for most people. And that is, you know, eating properly, paying attention to, you know, protein requirements and good quality protein throughout your lifespan. Exercising from a health perspective is very different than exercising for performance. So, when I was younger, exercising for performance involved, you know, big base for aerobic capacity, putting in, you know, 600, 800 hours of, you know, base endurance training, coming up to the activity, very specific, you know, 6-minute on, 3-minute off intervals, very terrain specific. You know that race is going to have a lot of hills and really getting into the minutia. Whereas, you know, as I started to get older, I think it it my research became much more clear. And that is that as we age, we need a combination of both endurance and resistance exercise. And so, simple things like titrating in more resistance activity as we age for an endurance athlete is going to be healthier than just sticking to the endurance activity. And the flip side, just doing weights, you're ignoring the beneficial effects of aerobic activity. And so, there's some really simple things I think that work across the spectrum for
individuals, for a population to be very healthy. Now, when you get down to the, as you say, the sharp end of the stick for specific sports, you know, your genes to a large extent give you a window of opportunity. So, for example, my window of opportunity was never to be a top sports sprinter. Sounds like you were much better sprinter. Your gene profile puts you into that window. But then there's infinite aspects that go into it. Injury. availability. I mean, you know, if you don't have a ski jump near your home, you're never going to be a world-class ski jumper, etc. You know, you stick a a dome for speed skating and, you know, that's where your speed skaters come from. They don't come from, you know, northern Ontario where there's no speed skating tracks. So, there's so many things that go into it, but I like your point about injury. So, when you think about the, you know, thousands and thousands of people that have incredible genetics, incredible VO2, even the opportunity for sports, but you twist your ankle on a walk, nobody can control that. And you start to accumulate various injuries. And to a large extent, I mean, you look at Jakob Ingebrigtsen right now, you know, best 1500 meter runner in the world. My understanding is, I've seen him at races, that he's got a calf injury. Doesn't matter how good you are, there can be this accumulated injury. And that's part of aging. All of us are going to get some degree of osteoarthritis. You know, for me, my big step to climb was I ripped all my hamstrings off at 42. That knocked down, you know, my fitness and my performance capacity. And so, that that randomness of accumulated damage that we all get is part of aging. And something that, you know, I think for most of us, you can work through it, but you have to give up the fact that, you know, at one point I was an elite athlete, that that will all we fall off for all of us. There's many examples of people who continue to to think that they're still going to be elite when they're well past their prime. And just accept and embrace aging
and you know, there's many things we can do to have a long health span and add about four years to our life span with proper exercise and nutrition. Age. I like yeah, that that the injury thread was is a good one. I remember the the first kind of real injury that I had it was it turns out I was combining martial arts with baseball and I had hypermobility in my lower spine that turned out I also had a spondylo - spondylothesis, right? So Uh yeah, I remember I was having the greatest game of my I guess I would have been what my 14 or 15-year - old career and you know, I had double triples and I was pitching that game and they were playing me to pull and I took it to the opposite field. Uh and I started to run down the baseline and it was like boom, back spasm and I got thrown out from the outfield. Here it is the guy who hit you know, stretched two two hits that game for extra bases and and then I remember going and seeing the specialist after and what he had said was something like we said two things it was like uh Doc, it hurts when I do this and he's like, well, don't do that. So it's like, okay. And then the other thing was well, hey, if you're going to go and do sport, you're exposing yourself to you know, the possibility of injury and so if that's what you're going to do, then you have to you know, go into that knowing that there's a higher risk and then on the flip side it's like, well, if you go to the other extreme, you do nothing, well, here are the consequences of that. And so it was always kind of like you know, walking that line between oh, I want to go to the Olympics versus how many surgeries do I need to have before I stop trying to do that, right? And then how do I you know, reorient on you know, as you say you know, the I like it as like you know, performance longevity. Well, Right. Okay, my my goal isn't to break 10 seconds. My my goal is to lift up my daughter and to play with her and teach her to dance and you know, teach her martial arts and
and so okay, what things do I need to do so I can do that for the next 20 years, right? And so that's like a that's I would call that an an upgrade, but you know, I do want to come into you know, how you how we can actually do that very personally and in in a way that I think it makes it very motivational cuz you know, sometimes it's I get maybe especially for the recovering athletes that say it's hard to take the generic obvious axiomatic advice and and do it because it's boring. And I think a lot of people well, I think what is it they say is to treat everybody differently is you treat everybody the same by treating them differently, so to speak, right? And and so like if I know I have a diet plan for me, you know, for not just my genes, but my goals and my injury history and my DNA, I don't know there's something special about that. Does that make me more inclined to do it? I'm sure that's going to be population dependent. But before we you know, the risk of going to granular, there's some you know, things that you were pioneering before it was cool. Like you mentioned protein. Like I don't think that was cool or even accepted when you recommended it. Yeah. And and yeah, how did that come into hey, eat more protein. I'm studying mitochondrial disease. Eat more protein like I was ever seen. Yeah, I would say it was sort of part of my earlier career as I mentioned in that fourth-year project with Dr. McDougall and then my PhD working on that. So at the time the US, Canadian and UK government said that protein requirements for sedentary people were exactly the same as top sport athletes. Now as a you know, former top sport athlete and I was a top sport athlete at the time, I thought that that was garbage. I looked at what my buddies and I ate and you know, we ate so many calories that our protein intake was was reasonably high and so we wanted to study it. Now at the time the
technology, which gets back to one of your earlier points, was to essentially go to the minimalist. So what's the lowest protein you can take to stay in nitrogen balance and that's how people determine protein requirements. So you go to a very low level and then when you cross a minimum floor, you actually start you know, burning more protein than you're actually taking in at that sort of threshold, that's what they call the protein requirements. So what we did is we looked at top sport runners who had a VO2 max of 75 mils per kilogram on average, so some really top top athletes and we looked at sedentary folks and we used the technology at the time called nitrogen balance, put them on different protein intakes to determine the median, then we added two standard deviations to cover the population. So two things came out of that. One, we suggested, which has now been proven by innumerable studies, that top sport endurance athletes need about twice the dietary protein intake versus sedentary individuals. A little less for females for complex reasons we eventually discovered, but nevertheless even the women need probably 70% more than the Canadian RDA if you're a top sport athlete. And we were or I was personally laughed out of meetings by the you know, the old British established nutritionist saying, well, when a British gentleman was taking a walk on the moor, their protein intake was also elevated, but again, you know, that's not top sport athletes. So it's a complete lack of understanding what it's like to train seven days a week, to be doing you know, two to three-hour runs on the weekend, intervals, a whole different kettle of fish. And you know, some people said, well, who cares it's a small fraction of population. My point as a scientist is well, I still think you know, we need we have nuanced nutrition. If you're a top sport athlete and you're told that you're okay on Canadian RDA, you're not. And we've done a study which I still have my post doc to to finally publish where we tried to put even moderately trained athletes on the Canadian RDA for a week and they couldn't even finish a week of exercise training, they were so pooched.
And that was one of the first areas that I was involved in. We also showed that the bodybuilders who'd been training for years and years didn't need as much protein as they thought they did and that was a bit of heresy at the time and I'm sure Joe Weider and others didn't like me because we were saying, hey, you don't need to be taking three, four, five grams of protein per kilo. You know, you're fine on about you know, 50 to 60% more than the Canadian DRI. So we really tried to I think nuance protein requirements for men, for women and as folks got older, there were a number of groups, Bill Evans, Art, my groups, Stu Phillips and others have clearly shown that as we age, we get something called anabolic resistance. And we also are seeing that in our patients because the muscular dystrophies, the inflammatory myopathies, etc., there's an impairment of our bodies' ability to take the amino acids from protein and to incorporate them into muscle protein. And so as a consequence, exercise is critical, timing of nutrition is critical and from a protein perspective, the quality of the nutrition is something that's really important because as you know, we've got the essential and the non-essential amino acids. We need a certain amount of leucine to help trigger protein synthesis, but then we need the other essential amino acids to come in. You know, I'm a big fan of of milk and mother nature. As humans, what do we feed our babies? Milk. And milk for a human is different than milk for a cow. So cows have mostly casein and a smaller amounts of whey. We have more whey versus casein. And Stu Phillips, myself and others have clearly shown that the whey protein comes in quickly, turns on protein synthesis, casein comes in slowly and attenuates protein degradation, so your net accumulation is higher. So protein requirements can be nuanced to the quality of the protein. They can be nuanced to aging and as we age, we need a little bit more and as we stress the body with different types of exercise that optimize adaptation, we do need more protein. And that can be nuanced too with timing. Immediately post exercise does tend to incorporate a
little more effectively the amino acids that we're taking in from protein. So that was really the first area that that I was involved in from a nutritional perspective. And now we're looking at obesity aging, muscle disease and showing that under all of these circumstances, it's even more important to be very very nuanced and and careful about the quality, the timing and the quantity of protein that one's taking in. Yeah, you know, as you're speaking and you probably experienced this as well, I think back to my athletic career and in the role of nutrition, I mean it cannot be understated. But after I I stopped competing, you know, I was on the other side of my track and field career and you know, just so fortunate to be exposed to all these disciplines like you know, martial arts, it was like taekwondo and boxing and you know, baseball, great hand-eye coordination and you know, but then I was the sprinter as we talked about before and swimming and I never you you know, I like the exposure to all those different disciplines gave me this wonderful physical versatility, the you know, the hypertrophy and the strength building obviously was cross-training for all these sports or I don't know if cross-training would be the right word cuz it was so mandatory in the sprinting. Let's say, but you know, when I was on the other side of competition and I mentioned I was kind of carrying all these injuries, I I went you know, as a let's call it a uh uh regeneration recovery strategy, I did one of these like fitness competitions. I wouldn't call it bodybuilding, I wasn't interested in you know, that kind of output. I was interested in symmetry and rebalancing kind of post-surgical and I was like, I'm I'm one of those people who really loves to have a goal, and so I said, "Okay, I'll do that the men's physique and uh you know, I really I dialed in my nutrition more there than than I ever had because like you could literally see the difference and once you start to and I'm not
recommending this, once you start to play with the the different macro uh nutrient ratios uh like in particular, there's a phase when you go kind of pre competition pre-stage readiness which is not to similar from you know uh say say racing in in the endurance sport, there's there's essentially a carbohydrate depletion phase and then a reintroduction and also with uh hydration and salt and and I was amazed to see like the body transformation in days and that it it just it it didn't stop like and then you're you're done competing, so I was like, "I'm going to keep eating." And that was a mistake. I As much as I had like a nutrition strategy like loading strategy, there really ought to have been an unloading strategy cuz it felt like I could just keep eating and everything was being shunted into my muscles and I was like, "Oh, I think this is how the beef cattle industry works when when they talk about you know, grass-fed grain-finished." Uh I mean it it just gives you a sense of just how amazing you know, the body is and just how quickly it can change, but then how much of that is permanent versus impermanent. In this case, it was really you know, muscle glycogen felt like it doubled or tripled in the span of of days. Like literally, I gained 20 lb in one day if you can imagine that just from hydration. Maybe not one day, maybe two or three days. I'm exaggerating. That's that well older you get better than you you were kind of thing. But so I wanted to give carbohydrates their due and also uh you know, fats as well where you start to hear a lot about um you know, suboptimal nutrition and trans fats and depleted micronutrients. And just given that we didn't even actually talk about and I wanted to make sure we covered a good amount of time talking about your your entrepreneurial pursuits cuz here you are, you've got the MDA uh sorry, the MD background but the PhD uh background and but you're also quite entrepreneurial in the nutritional space and making your solutions widely available and so you know, interested to
learn more about you know, how you've taken these research insights basic research insights but made them practical and accessible as an entrepreneur. Yeah, so one of the things that has always uh bothered me is uh false health claims and it is absolutely shocking and now and I see it even more, you know, where people are saying something is clinically proven and there's no clinical trial. So uh what happened uh about 10 years ago is decided to start a company uh and it was called exerkine. So I was the first to coin this term exerkine which are the proteins and the microRNA which go up in response to exercise. So it's a twist on a concept that Ben Peterson and uh Mark Febraio came up with uh the the 5 years before I coined the exerkine term. They called it a myokine. So they identified interleukin-6 as a myokine that came from muscle which then turned on gluconeogenesis in the liver and we now know it has anti-cancer effects and other things when it pulses with exercise. So the hypothesis was there are probably proteins and microRNA that go up when we exercise which confer uh some of the multi-systemic benefits. So uh long-term endurance exercise gives you 4 years of lifespan extension, 10 years of healthspan extension, lowers the risk of cataracts, cardiovascular disease, dementia. So these multi-systemic benefits uh must be something that's circulating. And so you know, I said, "I don't know if it's coming from the liver, from muscle, from fat. So why don't we just call them exerkines, anything that goes up in response to exercise." So we decided to try and profile uh these exerkines. We took blood from sedentary people, top sport athletes before and after exercise, put them on a Petri dish to see when they turned on mitochondria. Uh we found that it was more of the athletes which again is an adaptive response immediately post-exercise when we applied the serum uh that turned on mitochondria. So then we you know, did proteomics to try and figure out what the proteins were and we identified interleukin-15
as one of the main thing. I won't go through the science behind it, but eventually uh we gave that back in little pulses to mice and uh and it worked. It increased their muscle mass, uh it improved the mitochondria in their muscle and in their skin. So uh based on that, we said, "Well, why don't we just identify all sorts of exerkines, put them in a pen and then we can perhaps give back to our patients who have severe disease where they can't exercise." Uh I hate to use the term, you know, exercise in a pen and sort of like your Ozempic exercise injection. Uh so that was the concept. Uh we got involved in something called an exosome and uh we're trying to because we know that exosomes carry some of these uh proteins and microRNAs. So we're trying to use that as a gene therapy delivery mechanism. Uh we had a patient with mitochondrial disease for complex reasons proved that it could never work. Uh we went bankrupt and uh then we restarted again with more of the nutritional aspect. Uh you know, you've heard I've had this uh interest in nutrition, you know, back in the' 80s and know quite a bit about it. I've been following you obviously nutrition and doing work on it for for a long time. So Stu Phillips, uh my uh first post-doc, Johnny Parise, my first grad student, came up with a combination which we now call Muscle 5. And that's whey protein, creatine monohydrate. We published about 30 papers on that, vitamin D, calcium, and omega-3 fish oil. So they did a randomized trial in older adults where they did weight training which is obviously very good for people. We and others have shown you increase strength, functional capacity uh in and muscle mass in older adults when you weight train. But it was enhanced when they took this Muscle 5 versus collagen. So my wife and I took some of our uh money, we essentially bought the patent off of them. We reformulated it with my and I've already mentioned my evolutionary interest and I said, "Well, why don't we not use whey protein, let's use this humanized milk ratio of 60% whey, 40% casein so we can really optimize protein synthesis." We dropped
the protein amount from 60 g to 40 to make it you know, more attractive for women and for most people to take a slightly smaller amount. We replicated their study with a great post-doc that I had years ago, uh Dr. Mats Nilsson. And showed essentially that when we took this Muscle 5 versus collagen, we had better increase in muscle strength. We had better increase in function like going upstairs, getting up and walking 10 m and sitting down. And when we looked at the obese and overweight people, i. e. those who uh could be taking Ozempic, uh who would be eligible for it, uh we found that there was almost no benefit whatsoever to the collagen. They actually got more obese. Uh they didn't increase their muscle mass at all in spite of 3 months of weight training. And yet they increased muscle, decreased body fat, and improved performance. So uh with that, we then marketed this Muscle 5. Another clinical trial with an independent group used just that alone without the omega-3s in young people to show enhancement of muscle gains with weight training. Uh and uh recently, it hasn't been published yet, but another independent third party uh combined two things which I'll talk about, the Muscle 5 and the Trim 7 in uh overweight men and women who are eligible for Ozempic, gave them the advice that you you should when you take these GLP-1 drugs for weight loss and that is exercise, control your nutrition, uh and do you know, 180 150 to 180 minutes of exercise per week. Those who took again the Muscle 5 and this Trim 7 which is a mitochondrial enhancer uh gained uh more muscle. Uh women in particular, even more so than the men, lost quite a bit of body fat. Uh so it's really one of the only strategies that I've ever read about where you can lose fat but gain muscle. So if you take GLP-1 / Ozempic which most people have heard of, uh you will lose bone and muscle. If you um do bariatric surgery, you'll lose bone and muscle. If you just do a low-calorie diet, you'll lose bone and muscle. So uh the only way uh that we found in spite of doing exercise with those other
strategies, you still continue to lose, uh was with our combination. So those are two of the main products. We have a variety of other things, but I think the main thing that I want to get across is that we've done a very different approach which was to some extent not a smart approach from an entrepreneurial perspective and that is we tried to do a pharma nutraceutical approach. And what I mean by that is we have preclinical work. Uh we do safety studies from preclinical, we then do randomized double-blind studies uh with uh good clinical practice guidelines. We have independent third parties blind the stuff for us. So all of the things that give credibility and avoid quote cooking the books, you know, we apply. Problem there is you spend many millions of dollars to do these clinical trials and I've only mentioned just a few of the ones we've done. Uh and you can have some kid come out of grade 12, you know, make some false claims, you know, say that it's clinically backed, borrow someone else's science, and you know, have a good TikTok influencer and they can make 50 to 100 times more than we did. But ultimately, I do think that it's going to resonate with the population that's becoming more and more aware of what's real and what's not. But also with you know, some of the bigger players. You know, the Nestles of the world, the you know, Abbots of the world. These are folks who you know, will not be looking at products that aren't built and backed by science. And because of that, you know, we have patents on everything that we've done which costs a huge amount of money and we've got true real world clinical data in the populations that we're studying. And you know, probably the most most thing that we've done is the product behind me, the TRQ 7. Which you know, if we have time I can talk about it because that was based on our mitochondrial enhancement. So, to treat mitochondrial patients, I put forward a hypothesis in 2001, uh where treating neurologic disorders, we have to target these final common
pathways. Which interestingly enough, are you know, now well accepted as the final common pathways of aging, which is the mitochondrial disease we all have. And that is oxidative stress, mitochondrial dysfunction, inflammation, apoptosis, uh impaired proteolysis, decreased protein synthesis, etc. So, uh what we did is 2007, uh we gave to our patients with genetic mitochondrial disease coenzyme Q10, alpha lipoic acid, vitamin E, and creatine. And we showed that we could lower oxidative stress in these patients where it was very elevated, and we improved mitochondrial function. We then said, well, what about more common disorders? So, obesity and type 2 diabetes, again, these final common pathways are there in in fat and in liver, for example, in fatty liver disease. So, we did many preclinical studies with a whole bunch of different combinations of mitochondrial enhancers, antioxidants, and came up with the essential seven. Uh and then we did a randomized trial in uh younger men and women who were eligible for Ozempic, the overweight and obese category, and uh gave them the you know, typical guidelines for exercise and nutrition. And at the end of it, uh we found that the uh folks who lost weight on TRQ 7, uh lost only fat, but not muscle. And again, so that's by targeting the mitochondria. And in our preclinical work, it's pretty clear that what we're doing is activating mitochondria in the white adipose tissue, and that's called browning of adipose tissue. So, we're turning your fat stores from a storage site into a furnace, for lack of a better term. And we also, with my colleague Greg Steinberg, uh looked at fat oxidation was enhanced, metabolic rate was enhanced when uh they took this product in in our preclinical work. So, I mean, that's that's what we've been doing. Yeah, and that's pretty amazing that the uh What did you call it when you're you're basically the the brown fat synthesis? What what was the term for that?
brown So, browning of adipose tissue, Browning of adipose, yeah. I mean, that's that's what happens when women become pregnant, isn't it? To some effect. of adipose tissue, it it was first described in uh bumblebees, they have these inefficient cycles, and bears, they've got a lot of this brown adipose tissue. Humans have it, especially younger children, between this your scapula and your neck region. And they have lots of mitochondria. Now, we can't do much about our brown fat as humans, but most of us have tons, even as an athlete, I've got tons of white adipose tissue everywhere. So, by increasing the mitochondrial capacity a little bit in the white adipose tissue, uh we've got this huge metabolic furnace that we can take advantage of. And that's beigeing or browning of adipose tissue, i. e., we just increase the mitochondria. And uh and we've shown that in multiple preclinical studies. Uh in addition, uh we've shown in both preclinical studies by independent third party, very significant improvement in fatty liver disease, for which there's pretty much no treatment. Uh we also showed that the main markers of fatty liver disease were favorably enhanced in our clinical trial of the overweight uh men and women who were overweight or obese. Amazing. And you kind of Well, you took some somewhere that I wanted to go in terms of questioning uh around you know, what a lot of the the popular maybe non-scientifically backed recommendations are today. Like so I I mean, I I'll hear a lot of the clients that I consult with who you know, their their goal is longevity, so their ages 50 plus, on their way to 70, like, oh, should I take creatine, or should I take branched-chain amino acids? And there's kind of these like uh you know, single in pursuit of a single silver bullet type of solution, right? And and of course, I mean, it's not so simple. And I I remember actually being just fascinated by like, meat factor protein. It's like, what is it that helps iron absorption? Meat factor protein. Well, what's that? It's
like, well, we don't exactly know, it's some combination of proteins that it's available in meat. And you know, when you try to when you take iron on your own, the absorption isn't as good, so there's this meat factor protein, right? So, to me, it's like speaking to like synergistically what's going on to get the outcome, which again, it speaks to even what we saw with the athletes, right? Okay, well, you may be genetically predisposed to this, but what's your environment like? Uh you know, what are your behaviors like? Cuz I mean, you there could be behaviors that counteract, you know, everything that you're you're trying to do. Which I think that's what makes these clinical these double-blind clinical studies in nutrition in particular very very hard to con - to control for. So, I mean, kudos to you for for being able to do that, and to collect and to get patents on you know, the outcome, so that you don't just get patents, right? I mean, there has to be something patentable. So, Yeah. You know, interested to to I wonder how what you So, so you think about the the populations that you work with. And so, what I'm thinking about now is you know, this is big in the pharma industry now. Like I mean, everybody's hearing about what's going on with 23andMe and Regeneron purchase, and actually I don't know if they're trying to recapture it. I think we're going to find out actually if we didn't already find out. I think that was yesterday or or any day now. But yeah, like like pharma is is looking at genetics to you know, help with say, drug targeting, right? So, looking at genetic differences. But now there's also there's a future that we're going to see where everybody's DNA is sequenced from birth, right? I mean, how useful How long it takes for that to become useful is another conversation. But you know, like I'm like I said, I've been thinking about DNA for 25 years, so I I think I know some of the right questions to ask as it relates to my daughter's health, so I have an unfair advantage in in that way. It's not ready for primetime clinically, although
I will bring it in to conversations with the pediatrician, and actually add, you know, a layer of perspective that has led to very, you know, constructive conversation. But the the point that I'm going at with this though is even just like say, again, we're talking about the pharmaceutical industry, okay, for drug discovery, drug design, potentially. But then there's even, as we know, you know, differential response to to different pharmaceuticals. Like, we're learning more from, you know, polygenic risk scores, for example, that you you may do well to be on a statin sooner, whereas, you know, others, you know, genetically speaking, are not going to have the desired outcome from the drug, so they may require a different strategy. So, as it relates to Well, this is big in Canada right now, too, right? I think it was Genome Canada that announced some I can't remember what the number was, but close to, you know, 200 million in sequencing the population, understanding the diversity of the population. Do you see uh that access to omics data as something that is going to help or hinder the research that you're doing? Well, it there's many examples where I think that there are pharmaco-nutra - genomic interactions. Yeah. And uh you know, I've got two uh good examples. So, one that's very common, that's macular degeneration, which is a disorder that 30% of us will experience. Uh it's an age-associated disorder, start to lose your central vision. Uh again, all of the things, impaired autophagy, mitochondrial dysfunction, oxidative stress. And we are working on a strategy for that, again, with the multi-ingredient supplement approach. But the common medication came from a study called the AREDS study, and uh it's it's marketed as something called Vite + Lutein. So, the AREDS formula, on average, uh did slow the progression of macular degeneration uh in sort of the intermediate form. However, what became apparent is that there were two polymorphisms that were discovered where people actually got worse. So, you know, with a hand-waving, you go and you pick it up, go to Costco, you
don't know if you've got the polymorphism or not. So, 15% of the population, because of the high zinc content in the formulation, they were actually getting worse with uh with the formulation, not better. And so, when that became apparent, you know, a lot of the Well, some of the companies dropped the zinc from 80 to 25 mg, which is prudent, cuz that 80 is a little bit high. Uh but some of the ophthalmologists stopped prescribing it, and because they didn't have accessibility for this uh to find these polymorphisms. And the same is true of a disease we treat. So, for mitochondrial disorders, there was a synthetic form of coenzyme Q10 that was formed called idebenone. And again, about the same proportion actually do worse on idebenone from a different polymorphism. And uh so, uh you know, we've looked at that, and certainly in vitro, and we've clearly shown that our MitoCore, which is the alpha lipoic acid, coQ10, and vitamin E, and depending on the study, we often add creatine as well, uh works across those uh variants. So, whether you have those variants or not, they work. And I think part of why these work is number one, it's a mixture of what we have in our body already. So, everyone has these, we're just putting them into logical proportions at you know, that that mimic, you know, that what we're targeting based on, you know, lower doses versus high mega doses of single agents to get an effect. For example, uh we did a study in 2007 with that MitoCore. People criticized me, as they always do, and said, you know, we don't know which one's working. So, uh I said, okay, fine. We'll do just CoQ10 because everyone thought that's what was working. So, we used very high doses of coenzyme Q10 in a 30-person randomized double-blind crossover study published in in 2010. MR spectroscopy genetically confirmed patients data blinding GCP the whole bit showed absolutely nothing whatsoever. So, again hand-waving about a supplement doing X,
Y, and Z without clinical trial data is hand-waving. Yeah. If people don't learn anything from this podcast, number one, make sure whatever you put into your body if someone makes a claim about a supplement, go in and if you can't find a randomized clinical trial, don't believe it. And you see that with so many products out there. There's just no data whatsoever for them. So, people have to be very careful. And I think, you know, if we had some genomic data, I think we're going to understand, you know, where certain things like I've given the example of the AREDs formula or Vitalux and idebenone where it can actually do more harm than good. And then most people think, oh, you know, it's got a bunch of antioxidants in it, you know, this Vitalux is going to be great for me. How could it possibly do harm? But again, I think better knowledge of our genomic profile is going to help us from that perspective. Again, I don't want to see genetics used in the wrong way and that is if someone told me that my genetic makeup was to, you know, go running on pavement, I would say, well, screw you. I don't care. I think I hate running on pavement. So, I think, you know, there can be good and harm from it. I think if people then start to avoid things that they might like like, you know, a certain type of exercise because you're not genetically predisposed to it, that can do harm. And certainly from an exercise perspective, I think any exercise is good. I do I give kids a smorgasbord of activities. Let them pick what they like. And then people are going to do it for you know, throughout their whole life. We also also have to change society to make certain things more acceptable. I mean, recently do we have bike lanes? I mean, I've been hit by a car twice in Hamilton when there were no bike lanes. Accessibility, we need showers at workplaces. We need gym class you know, across the entire spectrum of high school. Now, you can't go out in Ontario after grade nine. Yeah. We're going to learn a little bit about that, but you know, we're we're getting a little bit off track, but you know, things that I'm very passionate about. I think that if
if we use genomics in the wrong way to slot kids or even, you know, adults into certain exercise programs versus letting them explore and enjoy, you know, because I think everyone's an athlete. You just got to find what you enjoy. For sure. The negative connotation we get with with exercise. Yeah. And and part of it part of the fun of that is the discovery process, right? I mean, and and you know, with respect to the athletic typing per se, I've never really been a fan of that. And and actually I only talked about the injury predisposition. I actually did the analysis on the different exercise response genes. And you would see world-class 800-meter runners with the sprint gene. And actually then in that scenario, it was like, hey, did you know that you could add this little bit of information to your race strategy? Like you could be a sit and wait kick at the end type of athlete cuz you've got this great engine that you built not genetic because necessarily you had the genetic predisposition for it. I mean, you leverage the environment to overcome your genetics. You're doing the sport that you love, but now if you add a little bit of this plyometric training, a little bit of this weight training, a little bit of this speed training, you know, your 200-meter kick could be like 22 seconds or 21 seconds. And you know, 20 point maybe for 800-meter run, that's amazing. Now, don't over index on it because you know, you still have the the load of the physiological, you know, VO2 max adaptation. You got to keep that going. And so it's like this minimal effective dose game. But that's what you're playing at the tip of the spear, which, you know, I would argue you're playing a version of that later on in life. Like, you know, you had mentioned, you know, it's one of these things is like, well, don't get injured because I mean, when I had a, you know, knee surgery shoulder shoulder surgery, it's like, yeah, 2 3 weeks of of, you know, inactivity is I mean, it's just drastic in terms of how much muscle mass loss is is seen in
that period of time. And so Just following up on that, not only muscle mitochondria. So, we did Mitochondria bones? Healthy men and women. Yeah, these are physiology students. We put in a mobilization splint on their leg for 2 weeks. Both. Within 48 hours, it was a 70% reduction in PGC1, main master regulator of mitochondrial biogenesis. At 2 weeks, enzyme activity and protein were down 25%. So, think about a 60 or 70-year - old who comes in for a hip or knee replacement and they're out for 6 or 8 or 10 weeks. They're already coming into it with muscle atrophy, you know, slight decrease in the nerve innervation of their muscle, mitochondrial dysfunction to begin with. Then you feel sick. weeks of immobilization. So, I think prehab, being active to begin with is probably the best strategy. So, you're coming into it with better muscle. Very active rehabilitation is just critical for older adults to overcome injuries which we're all going to get, but you know, suck it up, sunshine. Just keep going and get moving. The inactivity will further compound your aging process. Yeah, I mean certainly there's there's, you know, first principles that are you know, you ignore at your own peril, right? So yeah, how do we get more people active? How do we get more people to stay active? I I mean, for me and this again my bias is what has attracted me to it is just a genuine curiosity of like, wow, this is how life works. And so just constantly learning more has led me to explore more of, you know, what my body could do. And so, you know, the child in me the child curiosity is like, I want to pass that on to my own daughter. It's like, hey, your body is worth knowing. And and to your point, yeah, we don't want to misuse genetics, but I I think in the realm of like the nutritional intervention, that's that's a different story compared to, well, here's your the genetics of your physiology and
anatomy and only do those things. But with respect to the you know, this population of vulnerable people to macular degeneration, which is me, by the way. I'm like, okay, well, I have an appointment with my eye doctor next week and this is on my list of things to talk about. And so then I know I can look at my genetic profile and see if I have that vulnerability. So, should should I or shouldn't I? And and so, but then the ophthalmologist is going to say, well, I can't prescribe you that because there might be this thing. And it's like, well, it actually might be good for me. Like, yeah, well, I don't want to experiment. You want to do that on your own, go ahead. But then it could be like, but wait, here's the DNA. Right? And So, like how do we get to that future where we have responsible access and sharing of DNA cuz I for me, for example, I have access to my whole genome. I've loaded into my own large language model. And so when I go in and I get my surgery and and the anesthesiologist comes out and is like, hey, do you have any drug allergies? My running joke is like, I don't know. I haven't tried them all. But now now I'm like, actually, no, but show me the drug protocol. Like what are we doing and what's my patient? And give me everything then I can load it in. And it's like, oh, turns out Celebrex, I'm a negative responder to that. And I actually knew that, but I forgot about it that time when I had my labral tear corrected, I had a resting heart rate of like 160 and was burning up and had to go out for a walk like the day after my surgery because I was like, I I can't handle this. But I I thought it was something else. I didn't even think that that's what it was. But it was like, okay, let's kick out Celebrex and we'll throw in Benadryl if you need it, right? So, and then the other one is, you know, any of these like opioids, it's like keep those away from me. So yeah, I I again like I know Canada is investing into understanding all these diversities. And you know, my concern as
let's say a recovering academic is that's great, but how do we go from basic research and understanding to improving lives? And I've had lengthy conversations with this about this with well, people like Chris McMaster who you you probably know. He I think he's a chair of genome CIHR Canadian Institutes of Health Research. He's at Dalhousie University. Yeah, he he does work in the rare disease space. You guys would have a lot great things to talk about. But you know, it's his position that it's like, yeah, okay, well, we could have every newborn sequenced like today, but how do you put that into clinical care when doctors are already overloaded and they're not trained in it. And okay, what's the healthy balance between technology high-tech versus like the high touch and the responsible stewardship of that data. I mean, I ultimately see it as like at least this is how it is in my family. It's like, this is what we talk about around the table. Like my nutrient requirements are different than my daughter's are different than my wife's. And, you know, it's like you adjust the rudder a little bit today. That makes a big big difference 10 years from now. And it makes a big difference if you're an athlete 10 minutes from now. So, yeah, I I mean, I am that this is a a question that I I don't have the answer to. I'm just kind of putting it out there cuz I've seen all of these, you know, advancements or research collaborations starting to happen. And and I'm seeing, you know, like, hey, Canada could be, you know, this hub for innovation. They have all these you know, founder populations like in Newfoundland and Quebec and these new immigrant populations and and actually, you know, potentially very effective not even clinical interventions like like lifestyle interventions that can be optimized genetically today if we just had the right way of communicating it. So, Anyway, that It's a huge question. I mean, you know, it gets to newborn screening and
you know, talking about this at newborn screening Ontario, we're very aware that we can sequence genome in everybody. Big challenge is we don't have the genetic counselors or the doctors to handle. I'm part of the newborn screening Ontario. We're the regional center for screening for spinal muscular atrophy. So, 95% of the people who have this will have two deletions. Easy to screen for so we can rapidly screen in the population. Yeah. Now have an intervention. So, the intervention essentially takes the kid who's going to die at two years of age with SMA type one to all of my kids are walking now with the new gene therapy. It's just absolutely mind-blowing. However, that's one of 22, 000 genes. So, when you start thinking about the other if you can't do something about it, what is the value of knowing? And so, that's a bit of a challenge, right? Because, you know, some people may not want to know. There are a lot of people who just say look, I don't care what my genes are showing. I just want to go through life and just experiment and then not have this, you know, this sort of Damocles over my head that I'm going to get macular degeneration. And so, do you then grant that to someone the access when they're 16 and they can sign consent? Mhm. So many things that kind of But certainly from a newborn screening perspective, unless you are going to change the outcome, then it's not put on newborn screening. It has to be very carefully titrated in so that we don't overwhelm people cuz, you know, the average family doctor even, you know, your average geneticist who deals with this stuff, if you God, you know, some polymorphism in a gene, you know, is it pathogenic or not? You know, how are you going to prove that? And we just don't have I mean, we have large databases out there already that we can comb for new variants, but even those are sometimes really problematic and a huge amount of work. But there are instances where it makes sense, but certainly from a nutritional exercise perspective, my feeling as, you know, pediatrician and an adult medicine specialist is wait till you're at the age of consent. Let kids be kids. Let
them play. Let them make mistakes. Let them do all these things. It's not going to harm them for the rest of their life. When they're 16, I think we can start thinking about, you know, titrating in some more information to these individuals at a time where, you know, they can still make some changes if they so desire, but it's informed consent is is Yeah. I mean, that makes a ton of sense. And in in the in that scenario, do you imagine uh, you know, given how far your research has come, do you imagine it like like it you well, you probably already have like some kind of omics models where there there's, you know, different gene markers that you look at collectively, different methylation profiles, like oscillation profiles. Like you probably have a sense of what those models are already. Is that fair to say? Yeah, I mean, there's two different parts to this. I mean, one is obviously, you know, diagnosis of rare genetic disease, which is one aspect of my life. You know, some of these other changes that occur that are more lifestyle associated. So, changes in diet, how does that affect methylation? You know, For example, you know, one really horrible McDonald's meal can alter methylation overnight of your DNA and change how how it's expressed. And you know, getting a better understanding of the entire omics profile from, you know, microbiome, your metabolome, your glycome, your proteome, and you know, your genome and how those all interact is going to be massive. And then AI is going to help us, but it's it's going to be such an interesting and exciting areas to move forward. You know, to a large extent, too, I think if these can be used from a motivational perspective. So, let's say for example, we know that top sport athletes have this, you know, microbiome or this metabolome. And if you're sedentary, you have this. Can you then have a score Right. gives you a health span score. We're working on something similar called the body composition index where
we're trying to find the appropriate ratio between fat and muscle, which most people want more muscle, less fat, and coming up with the thing we call the body composition index, which relates to knee extension strength, which relates to fall risk, which relates to VO2 max, which predicts, you know, health span and lifespan. And so, that's one of the areas we're moving towards is coming up with this body composition index, but I would love to have, you know, a multi-omics index, not just one or the other because there's pros and cons to all of them. And I think AI could help us come up with the optimization across a variety of omics profiles to say this is a healthier omics profile. And you know, then what what can do is try a nutritional intervention in that individual. Check and see. And I think that's the important thing, too, is to get towards personalized medicine with these where you could try a certain exercise program with the room at a higher protein or different type of protein and see does it favorably enhance your methylation profile? And part of the advantage, I think, is we're probably going to see changes in some of these profiles, obviously not the genomics, but we'd see changes, let's say, in glycomics or metabolomics or microbiome, which is crazy. Like when we still have to analyze this, but with Trim 7, probably the most consistent thing within days is you can feel your guts change. Mhm. Constipated become more regular. I've got IBS totally gone when I'm on it. So, that changes very rapidly. So, you don't have to wait three months the outcome. Mhm. Check and see is it working in a favorable way? I can see lots of really exciting opportunities. Yeah. dark side, but there's so many benefits. It just has to be titrated carefully and appropriately to to individuals. Yeah, 100%. I mean, I did uh when I was I did my postdoc in Cornell with Ruth Ley, who was Jeffrey Gordon's understudy, who was the pioneer of of gut microbiome metagenomics.
Uh, we did the first taste study of how the infant gut is colonized. And it it was a hypothesis outcome study, right? So, it was observational. It was just basically, you know, three years of tracking the infant gut microbiome. And then when you look at it in reverse, you're like, wow, here are all of these environmental factors, changes in nutrition, introduction of antibiotics because of ear infection, you know, changing out uh, breast milk to cow's milk to formula. And it's just like boom, And and you could see you know, the hypotheses were, you know, and then this was it done in collaboration with the human microbiome project, NIH-funded initiatives. Some great labs. You got a picture of what a healthy microbiome looked like and it wasn't necessarily specific species. Maybe it was more like different phyla. And really, if you go up to the top, the main principle, first principles is really like what's the diversity, uh, you know, and then well, how do you define diversity? And then you might say something like, well, what's the resilience or what's the recolonization capability? How quickly can you do that? And you know, how far gone is too far gone? Like a C. diff is like, well, how do you Well, you can't recover that. That's like those are, you know, healthy donor uh, gut transplants. Gut transplant there. But so, it's a it's about it's like to your point with the methylation, it's like, well, it could change overnight. So, what if you happen to catch a bad one or a good one? So, how is that metric even in how is that informing the situation? And But but all that being said, I look at there's Henry Ford's Model T with basically a I doubt he even had a gas gauge, you know, and then you've got Tesla, which is like I can like upload from the cloud based on, you know, the new research that we're doing that by the way, Tesla, as I understand, is not really a car company. It's a robot company. And there's all this data that they're collecting and and so, there's that aspect of it. How much of your data do you want to collect and share? And And well, if you're an
athlete, it's like I work with some, you know, top table tennis athletes that they want to know Actually, they don't want to know any anything. They want their coaches to know everything and make the decision. And that's something that they've agreed to because they want to be like Tom Brady and have their career as be as long as possible. And by the way, that's not a longevity decision. That's a performance longevity decision, which is different than a health span. So, there's all those interesting questions like, well, what are you actually trying to do? But at the end of the day, one of the things that I've seen is like great, you know, brilliant scientists, researchers, medical practitioners such as yourselves, you have a lot of great proof, intuition, and proof of, you know, metrics that matter. And then so, it's like, well, how do we you know, how do we make that, you know, speed of market responsible and, you know, not the TikTok influencer dominated. So, definitely a conversation for another day, but you know, the before we want we we wrap up here, I wanted to, you know, check in in those top three questions, right? So, if this was our our last podcast, what what would we want to say to people here? What would you want to say to people? And Who does who should the message reach? Who needs to hear this? And then of course, the third question is who might you recommend as my next guest? Yeah, I think I'm kind of split between the first one. One is all kids are athletes. Give them a diversity of the of sports and let them pick what they enjoy. And the second, which is equally important, is on the flip side of that for older adults, and that is it's never too late to start always get benefits from doing this activity. So, that would definitely be you know the the answer to the first question. I I I'm sorry I had to split that into two, but there That's okay. No, it's okay. Yeah, and then you know in terms of who would be the person to chat with. Yeah, it's that's a tough one. I thought back and forth many times. I think you know certainly I think my my first postdocs to Phillips would be interesting person a lot of you know careful thoughtful information
on protein requirements. You know, he'd definitely be an interesting person to have on the view as well. And sorry the third question? You answered them both. What what was it who needs to hear it? You answered I got a two for with that one. So, now we're clear. Okay, well great. I'll I'll you know definitely extend the invitation for your recommendation and we'll we'll look to invite him on the show. But you know I Thanks so much. Appreciate it. All right, we've just journeyed through the science of vitality from the powerhouse of the mitochondria to the frontier of translational medicine. Dr. Tarnopolsky has packed painted a vivid picture of a future where aging is not a passive decline but a negotiable process. The vision he has laid before us of a world where lifestyle interventions are prescribed with the same precision as pharmaceuticals is not a distant dream. It's a reality taking shape in labs and clinics. The responsibility now shifts to us. Knowledge has been shared, the path illumined. It is up to us to walk, to advocate for it, and to build upon this foundation. The future of health is not something to wait for. It is something to create. And the work begins now.
Transcript auto-generated by YouTube. Verbatim — duplicates intentionally preserved.
In this conversation with Dr. Jeremy Koenig, Tarnopolsky connects decades of neurometabolic research with the everyday practices that shape healthspan. Exercise, protein, mitochondria, and genetics are not separate stories. They are one system of adaptation.
Mitochondria produce cellular energy, but they also respond to the environment around them. Movement asks them to become more efficient. Endurance work supports mitochondrial biogenesis. Resistance training protects the tissue that uses that energy.
The felt result is capacity. Stairs feel easier. Training feels more available. recovery becomes less fragile because the cell has been asked, repeatedly and intelligently, to adapt.
Muscle is not simply something we keep for performance. It is one of the body’s great reserves of resilience.
Muscle stores glucose, protects joints, supports metabolic health, and gives the body a reserve when illness, injury, or age creates stress. Tarnopolsky’s clinical work with neuromuscular disease makes the point sharper: preserving muscle is preserving function.
This is why resistance training belongs inside any serious longevity conversation. It is not cosmetic. It is structural resilience.
The episode discusses protein quality, leucine-rich sources, and the practical value of giving muscle the raw materials it needs. Training creates the request. Protein helps answer it.
For most people, that means distributing protein across the day rather than leaving the body under-supplied for long stretches. The details can vary, but the principle is steady: recovery requires materials.
Tarnopolsky works close to genetics, but the conversation keeps returning to gene-environment interaction. DNA matters. So do exercise, nutrition, sleep, and the repeated choices that influence expression over time.
That is an empowering distinction. We do not control every variable, but we do influence the environment our biology has to interpret.
The discussion touches on nutraceuticals and exercise mimetics, but Tarnopolsky’s standard is disciplined: claims need human evidence, careful study design, and measurable outcomes.
That restraint is valuable. Longevity will keep attracting bold promises. The better path is to respect emerging tools while keeping the foundation clear: train, nourish, sleep, measure, and adapt.
Treat resistance training as a healthspan practice, not only a fitness preference. — Practice note
Pair training with adequate protein across the day so adaptation has the materials it needs. — Practice note
Treat resistance training as a healthspan practice, not only a fitness preference.
Pair training with adequate protein across the day so adaptation has the materials it needs.
Use emerging longevity tools cautiously, and give more weight to human evidence than mechanistic promise.
