The Dr. Hyman Show - The Supplement That Reversed Aging in Human Trials, with Dr. Anurag Singh

Episode Date: June 25, 2025

On this episode of The Dr. Hyman Show, I sit down with Dr. Singh—Chief Medical Officer at Timeline and a pioneer in mitochondrial science—to talk about what’s really driving fatigue, muscle loss, and accelerated aging. Together, we break down the simple, science-backed ways to support your cells so you can feel stronger. You’ll learn: • Why your mitochondria impact energy, metabolism, and how you age • The role Urolithin A supports cellular renewal—and what that means for your strength • How you can pair fasting, movement, and nutrients for better energy and recovery • Why personalized strategies can support your energy, focus, and strength over time This episode is packed with takeaways for boosting your cellular energy—and it’s one of the most practical conversations I’ve had on the science of longevity. View Show Notes From This EpisodeGet Free Weekly Health Tips from Dr. Hymanhttps://drhyman.com/pages/picks?utm_campaign=shownotes&utm_medium=banner&utm_source=podcastSign Up for Dr. Hyman’s Weekly Longevity Journalhttps://drhyman.com/pages/longevity?utm_campaign=shownotes&utm_medium=banner&utm_source=podcastJoin the 10-Day Detox to Reset Your Healthhttps://drhyman.com/pages/10-day-detoxJoin the Hyman Hive for Expert Support and Real Resultshttps://drhyman.com/pages/hyman-hive This episode is brought to you by Seed, Pique, BON CHARGE, Paleovalley and Timeline. Visit seed.com/hyman and use code 25HYMAN for 25% off your first month of Seed's DS-01® Daily Synbiotic. Head to piquelife.com/hyman to get 20% off + a free beaker and frother today. Go to boncharge.com and use code DRMARK to save 15% on your PEMF mat today. Get nutrient-dense, whole foods. Head to paleovalley.com/hyman for 15% off your first purchase. Support essential mitochondrial health and save 20% on Mitopure. Visit timeline.com/drhyman to get 20% off today.

You're saying that you could take this compound made by bacteria as a supplement. You're going to see about a 10% improvement in strength in cardiovascular fitness and a reduction in inflammation. Mostly the trials we have run in placebo-controlled randomized trials, we see in the absence of exercise, in the absence of changing their diets, you get about a 10-12% improvement in strength. You get about a 10% improvement in VO2 levels. Leading immunologist, Dr. Anurag Singh. Explores how mitochondria and inflammation

shape our health. Aging and energy. Exercise is the best mitochondrial drug. So just getting people moving in their 70s and 80s, three times a week for 30 minutes, that's the basic, you know, having a rejuvenation effect on the mitochondria. You've got three ways to sort of soup up your mitochondria and make more energy.

One is exercise. Two is. In functional medicine, we always start with the gut. It's at the core of nearly every aspect of health, from digestion and immune function to brain and skin health. Your gut microbiome regulates inflammation, absorbs nutrients, and maintains the integrity of your gut barrier.

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Just open Apple podcasts and tap try free to start your seven day free trial. Hunter, I welcome to the Dr. Hyman show. It's great to have you. So we're going to talk about one of the most important things that almost nobody really understands today in terms of your health, longevity, well-being, energy, brain function, immune health, and pretty much everything. It comes down to something that actually is a topic that I love, which is how our bodies make energy, the problems that happen with energy and the little

tiny organelles, like mini organs systems in our cells that make energy called mitochondria. Now people hear that word, they probably think of high school biology. They're like, what is he talking about? Maybe they remember something called the Krebs cycle or the citric acid cycle, which is basically how your body turns food

and oxygen into energy in these little tiny factories, energy powerhouses in your cell. And we kind of learned about it in medical school and then we promptly forgot about them because unless you were some specialist dealing with some rare inherited genetic mitochondrial disease, you've never thought about it, you never treated it, you never diagnosed it,

and you never paid much attention. And yet, it seems that mitochondria, as it turns out, are probably one of the most important things you do need to pay attention to if you wanna live a healthy and long life. We're gonna kinda dive deep into the mitochondria today, what it means, what it is, what we can do to optimize it, what new innovations are in the marketplace

that help us to actually work with our mitochondria better and soup them up a little bit and clean them up, which is important, and how they play a role in so many diseases, including aging. So kind of let's start with the work that you're doing around mitochondrial research and why it's so central to aging

and why don't we talk a bit more? Well, I'm also a trained physician and so for many years. You're MD, PhD, so you're like a double doctor. Well, as you said, medical schools briefly educate the students, the future doctors about, you know, this is the biochemistry class and they learn about mitochondria. But I actually think, you know,

and we talk about these biological hallmarks of aging, these 12 biological hallmarks of aging a lot. I actually think mitochondrial dysfunction and the lack of energy and fatigue as sort of we age is the root cause of the central hallmark of aging. And the studies I have done, whether it's with old people looking at their muscles or their brains, every time you look at a 70 year old

who's exercising versus a 70 year old who's sedentary, frail, the answer is always mitochondria. That's right. Or even you're looking like, why is a two year old running around bouncing off the walls and a 92 year old just sitting motionless in a chair? The answer in a sense is mitochondria. The number, function, and activity of the mitochondria.

And so these are, as you said, these are powerhouses of the cell and they are really the energy provider. These are the batteries, right? So think of your cell phone battery, right? When it's all green, you can make a number of calls, you feel confident about your phone on a daily level, but the moment it gets red, that's when you worry.

That's exactly what aging and mitochondria is happening, the green is becoming red. So your body battery kind of- Fatigues out and you have to recharge it. And doctors for sure don't really know how to diagnose problems with the mitochondria. Or even symptoms that relate to mitochondria. But one of the most common presenting symptoms

the doctor is fatigue. So just to summarize, you've got three ways to sort of soup up your mitochondria and make more energy. One is exercise. Two is inducing mitophagy. And three would be. I think other supplementation strategies. Supplementation strategies like creatine, carnitine,

coqutin. So can you talk about the kind of symptoms that people might have if their mitochondria aren't up to snuff? Fatigue and a lack of energy, as they say, you go through the emotions of the day and at the end of the day, you feel like there's not much fuel left in the tank,

that feeling that's mitochondria, the energy deficit you have created during the day. The second is if you were to, if you're one of those who exercise a lot as you age, you start realizing that it takes longer to recover from an exercise. That's because your mitochondria are not in that perfect sort of balance between the bad and the good mitochondria, and now you have accumulated the bad mitochondria, and so you're taking longer to recover from exercise. The other things are, if you know, at the whole body level, just brain fog.

You know, for example, the muscle in the neuron cells have the highest density of mitochondria, thousands and thousands of mitochondria in a single neuron or single muscle cell. I think it's like, what is it, 17,000 of these in every brain cell? In every, and close to 10, 15,000 in a skeletal muscle cell.

So imagine that much energy that just goes away. And so that contributes, I actually think brain, muscle muscle and more data now you're seeing in the immune, these are the three key elements that will dictate our health span and how the mitochondria are functioning in all these three. In terms of what you described as the hallmarks of aging, the things that go wrong as we get older that can explain most of the diseases of aging. So we tend to think about things downstream. Okay, you've got heart disease, you've got Alzheimer's, you've got Parkinson's, you've got cancer,

you've got diabetes, you've got all these horrible things that happen as we get older, but we don't think upstream. What do these things have in common? There may be just different manifestations of the same problem, depending on the person. And it turns out that most of these conditions at the end of the day come down to problems with mitochondria and inflammation,

which are linked, and we're gonna talk about how they're linked. You know, when you really look at all the hallmarks of aging, there's sort of meta ones, and there's secondary ones, that's how I think of them. I don't really see them described that way, but everybody's trying to see them all as separate or different, there's stem cell exhaustion

and telomere shortening and epigenetic changes and there's microbiome changes and there's mitochondrial changes and protein changes and inflammation. This is a whole list of these that I've written about in my book, Young Forever, and it's really useful to understand them, but one of the meta frameworks that can explain even mitochondrial inflammation is nutrition. They call these deregulated nutrient sensing,

which is a fancy bunch of jargon for meaning that your body and your food aren't working well together and that the food you're eating is messing up your body, particularly causing inflammation and causing mitochondrial dysfunction. So when you look at diseases like Alzheimer's or diabetes or even cancer, these are fundamentally ultimately mitochondrial problems and the treatments can be mitochondrial treatments,

but again, as I said, no, we don't learn as doctors how to treat our mitochondria. We're even gonna diagnose them. What is the way that people can think about even diagnosing mitochondrial problems other than your history and your medical symptoms or your diseases? So mitochondrial functional testing is still

in its early days, we're still learning how to high throughput it, right? Like if you were to go and get your lab work done, you'll do a standard lipid profile, kidney profile, cardiac profile. Mitochondria is today not part of it. Inflammation is, so you do look at C-reactive proteins and inflammatory cytokines. So there are new tests coming out, there are folks working on buckle swabs for example, looking at the mitochondrial DNA content in your

buckle cells. There's a group called, I believe, MeScreen that is using blood cells to look at how the mitochondria are behaving in the blood cells to give you sort of an idea of how your mitochondria at a whole body level are. The way I do it in randomized placebo control trials is a few ways. So I would put, for example, older adults in an MRI scanner kind of setup, and they'll exercise there. And I can actually, using something called resonance spectroscopy, I can actually go into the muscle

and look at the depletion of ATP, which is this molecule of energy. And how fast after they stop exercising, it comes back into the muscle is an indicator for me how good the mitochondria are. Because if your mitochondria are not good, it just takes longer. And that's how in a lot of clinical studies today,

let's say investigators or translational investigators are studying mitochondrial health, this, you know, looking at the ATP recovery rate. And ATP is the energy, is the basically the- It's the molecule of energy, yeah. Now, the other way is you take chunks of tissue. So that's what I do, I go in and take a muscle biopsy. Muscle biopsy, that's fun.

Which is not fun, which is not easy to convince people, but believe it or not, in clinical trials, older adults who have problems with fatigue, they're very motivated and they volunteer. And what you see blows your mind away because you look at 30,000 genes in the skeletal muscle and you ask in an unbiased way, what are the top 30 pathways that are downregulated?

They are all mitochondrial length. And that, just not us who has shown that, it's multiple groups that have shown that, as we were pointing out, I mean, these hallmarks of aging are like a subway system and they all intersect in the middle with mitochondria and inflammation. Yeah, I think it's so important because, you know,

as a doctor, I've been trying to look at mitochondria for many years in functional medicine and we'll do, for example, VO2 max testing. You can do that. Which is a maximal exercise testing where they measure oxygen consumption and carbon dioxide production as an indirect way of looking at your mitochondrial function.

What we do know is that VO2 max, which is basically how much oxygen you consume per minute per kilogram of body weight, is one of the best predictors of longevity. It's in a linear way, the higher the number, I mean the more fit you are, the more your mitochondria can consume oxygen and produce energy, the longer you're gonna live.

That's pretty cool. And yet, that's a little bit of a more difficult test to get, but you can get it at gyms. Yeah, we do that as well. And I think that's helpful. Also, we used to look at organic acid testing, which looks at sort of mitochondrial function by looking at a urine test.

There's also labs in Germany that do extensive mitochondrial testing, looking at the mitochondria inside white blood cells in your blood and looking at how they're functioning. And you can see that it's a lot of mitochondrial diseases. I mean, we didn't talk about it. We talked about some of the disease of aging, but mental health is now an area of deep research

around mitochondria and cognitive function, not just things like dementia, but autism. It's found to have been really in part driven by mitochondrial dysfunction in these kids. They have a brain defecit. And Suzanne Goh showed this, who's a Harvard Oxford trained pediatric neurologist. She's been on the podcast.

And Chris Palmer, Ian Campbell, have been on the podcast talking about metabolic psychiatry where depression, bipolar, schizophrenia, these are mitochondrial diseases. And by treating the mitochondria with diet and other approaches, they can actually improve their function and help mitigate or relieve or put these diseases in remission,

which is pretty remarkable. The mitochondrial medicine is this area, it's sort of so promising and yet so neglected in traditional healthcare. And that's what's so great and yet so neglected in traditional healthcare. And that's what's so great about the work that you've done and that you're doing around the research. And one of the things I think you sort of mentioned that in passing I think it's important to double click on

is sort of new discoveries around the immune system's function and mitochondrial function and how we've been surprised by some of the things you've found around this? Because when you look at aging, these are two things that really happen. We lose energy and we become more inflamed. We started off thinking these were two different pathways because every randomized study we were doing,

now as you mentioned, diet and exercise are the two biggest mitochondrial rejuvenation drugs, if I can call them, that exists out there. My favorite drugs, diet and exercise. The problem is it's very hard as a doctor to convince everybody to stick to it, and you see very poor compliance in the long term. And so you have to improve your cellular health and your mitochondrial health with other strategies, nutrition being one of them.

So we started looking at it, and what we saw is that every time we improved mitochondrial health, the inflammation levels were lower in these folks. Now, whether they were 80 year olds, whether they were overweight, obese individuals or even athletes, believe it or not, even athletes where you think they would have the peak of mitochondrial or vice versa, improving mitochondrial health, we're still studying which are they closely interlinked or are they one precedes the other. But there is clearly a very close interaction between these two pathways. Yeah, and one of the fundamental hallmarks of aging

is this phenomenon of cellular senescence, otherwise known as zombie cells. These are cells that should have died and been recycled that seem to live forever and turn into zombies and then go around creating more zombie cells. And what these cells do is they spew out buckets of inflammatory molecules around the body. They're like basically pouring gasoline everywhere.

And that's a disaster because it's sort of a feed forward cycle. And that's a disaster, because it's sort of a feed forward cycle. And somehow what you're saying is that mitochondria play a role in this, either as a cause or a consequence. And so, you know, in medicine, we like to be very reductionist,

but the truth is that anything that causes inflammation will cause mitochondrial dysfunction, and mitochondrial dysfunction itself, if I'm hearing you correctly, also drives inflammation. Yes, really these damaged mitochondria that become leaky and the damaged mitochondrial DNA, I mean mitochondria have their own DNA, that leaks out into the circulation

and causes inflammation. And vice versa, inflammation can also be seen as a stressor for mitochondria that damages these mitochondria. So I think it's like a circuit loop between these two pathways. Let's back up at a meta level and look at, you know, if these mitochondria are so important to our overall

wellbeing, to our energy, to our brain function, to our mood, to our metabolic health, to, you know, pretty much everything you can think of, and yet they're so fragile, right? What are the things that drive mitochondrial dysfunction? What causes mitochondrial aging and breakdown and damage? So there's this sort of, this may be a bit nerdy, but this is what is called the oxidative stress pathway.

So as the life cycle of a mitochondria, you have the yin and the yang always. You have the healthy mitochondria, they're young, new, producing a lot of energy. Poor diet, you know, if you're eating a lot of processed food, etc. or your sedentary habit. They accumulate what we call as ROS or reactive oxygen species and they start becoming, as you were saying, zombie mitochondria. And over time, the body has an evolutionary pathway called mitophagy that should clean these damaged mitochondria out in the favor of more new or healthy mitochondria.

But with aging, this balance shifts to having more damaged mitochondria and they occupy the real estate in the cell. And what happens is now suddenly you have all these dysfunctional mitochondria but they're not producing energy. And that's why the whole sequel for energy, low fatigue, et cetera, sets in with age.

So basically, the problem is that as we age, we accumulate more damaged mitochondria. And people have heard of time-restricted eating, or intermittent fasting, or maybe they've heard me talk about mTOR, things like rapamycin, and other compounds for longevity. What they do is talk about mTOR, things like rapamycin and other compounds for longevity. What they do is they inhibit mTOR, which is a longevity pathway.

And what that does is that induces what we call autophagy, which means cellular cleanup. So it's like recycling of your damaged cells. But what you're also saying here is there's also a mitochondrial recovery process where we're supposed to be chewing up and eating up and like Pac-Man recycling our old and damaged mitochondria, but often that doesn't really work that way.

And we accumulate more damaged mitochondria and that in and of itself causes us to be more tired, fatigued and have mitochondrial symptoms and also accelerates in a few forward cycles more mitochondrial damage, right? Inflammation and the other senescence is all interlinked. But there's other causes for mitochondrial dysfunction besides just lack of recycling of the old mitochondria.

So what other? Yeah, so there are three ways today you can improve mitochondrial health and this is really, one is you can improve what we call biogenesis so you can can kind of seed newer healthy mitochondria. And so there are strategies, exercise being a very powerful, this is the whole PGC-1 alpha pathway where you stimulate this mitochondrial biogenesis,

you can improve the growth of newer mitochondria. Then there is sort of the fission and fusion. In English, that means that if you exercise, you stimulate a pathway that makes new mitochondria, that helps you create new mitochondria. And more energy. So that's kind of where the field is split into three ways. One, where you have these NAD boosters,

compounds like resveratrol, at least from a nutrition perspective, or metformin. They're all hitting this sort of AMPK mitochondrial biogenesis pathway. Then you have this mitochondrial efficiency. So you take the pool of your mitochondria that are already functioning well, and you get them to produce more energy.

So there's this idea that you can supplement with creatine or nutrients like L-carnitine, CoQ10, that are integrated into the different mitochondrial cycle. You know, there are five units of mitochondria and they all come together. And so you can make them more efficient. And then there's the mitophagy part. Now there are many ways you can combine these together as well.

Before we get too much more into how to fix your mitochondria, I wanna sort of just kinda double down on what are the other things, like our diet, toxins, stress, sleep issues, what are the ways that our mitochondria become more damaged in our current environment and lifestyle? Yeah, I think you highlighted diet is the number one, and lack of physical activity.

So when you say diet, what do you mean? Diet means not eating a good, fresh from the farm kind of rich in fiber. Fiber nourishes our microbiome. And that's how we, a lot of the mitochondria or ancient bacteria that had this great relationship with the host, which is us. So the way they process the nutrients

and when they get stress and damage, that impacts. That's how diet is playing. Now, physical- Diet, I would just say, it's the sugar and starch and the excess calories that overwhelm the mitochondria. And also the oxidized foods we eat, like oxidized oils and processed foods. People talk a lot about seed oils.

In and of themselves, they may not be the issue. It's how oxidized they are. They other words, they go rancid. Are you eating rancid oils? And that, a lot of the ones we eat are. And that causes more inflammation and damage to the mitochondria. So the fats you eat play a big role in what your mitochondria are made of

and how resilient they are. If you're eating crappy fats versus good fats, like omega-3s or even some saturated fats. So eating a highly processed, high sugar and starch diet and a lot of extra calories, that will overload your mitochondria. Of course, yeah. I mean, we see that in the whole diabetic pandemic.

Sugar is the biggest stressor. It's important you mention that because when you look at mitochondrial function in diabetics, it's like half of the normal population, half. And today the technologies are advancing, so we do something called metabolomics and we can actually find these mitochondrial metabolites in circulation, things like fatty acid oxidation

derivatives that show up in our bloodstream. So we can use, and we see that the impact of diet. The other one where we see is physical activity, big time. The impact of inactivity on mitochondrial health is not talked about a lot, but I think it's immense in addition to diet. I think that's the number two thing that contributes to how good or bad your mitochondria are.

And that's why exercise is such a longevity drug. It's not just great for your cardiovascular health and metabolism, but it actually is incredibly important for keeping your mitochondria functional and healthy and operating at the right level. Yeah, and you mentioned sleep. I think sleep is a very understudied area of mitochondria in the mitochondrial space that how your sarcadian rhythm,

how your sleep patterns affect mitochondrial health and how some of these pathways point to people. So we are actually now thinking of studying a group of individuals who have sleep disorders. And the professor who came to us actually found that these folks actually all 20 years after sleep issues, they turn into neurodegenerative disorders. So they either get Alzheimer's or Parkinson, and the fundamental root causes mitochondrial imbalance

in their brain that triggers these sleep imbalances. So I think that's another key area. So what you're saying is mitochondrial dysfunction can cause sleep issues or vice versa, or both? Or both. I think it's kind of interlinked. I think lack of or poor sleep contributes to worsening mitochondrial health,

and that kind of triggers this whole journey and acceleration to neurodegeneration down the road 20 years after, you know. So I think sleep is a key area. What else? I think toxins, of course, a lot of damage from the sun. You know, we have all these fluoride discussions today and all that. We see that actually if you put some sodium fluoride in the muscle cells or any kind of cells,

the mitochondria get stressed. So there's all these things in there. Yeah, pesticides, heavy metals, these mitochondria are very sensitive. They're very delicate. And they're very sensitive. And they get screwed up pretty easily by any kind of insult, including the load of environmental toxins we're all exposed to, whether it's the PFAS forever chemicals, whether it's heavy metals, whether it's synthetic toxins, flame retardants, pesticides or besides.

These are things that are ubiquitous, we're all exposed to. And they are hard to get rid of. But you can reduce your exposures. And then there's the microbiome, which is something that people haven't really talked about much, but when I did some homework and looked at the literature on this, because I would see this clinically, that people had microbiome issues,

it did affect their mitochondria. Well, that's how we got into the space of discovering compounds that were made by the gut microbes. So you're right. And I started to talk aboutbe. So you're right and I started to talk about it. So most mitochondria are ancient bacteria that kind of integrated with the host, right? So they have this what I call, and I started studying what I call the 3M axis, which is muscle mitochondria and the microbiome. So I actually see the microbiome as a polypharmacy.

So I actually see the microbiome as a polypharmacy. Okay, so a lot of, let's say, focus has been on prebiotics and probiotics and how you should modulate to have a healthy gut microbiome. I actually think it's what the gut microbiome is producing. Yeah. It has immense effects on mitochondrial health and beyond. I know many of you are as focused on recovery and longevity as I am, especially when it comes to managing pain and optimizing healing. After a recent back procedure, I needed something to help support my recovery and ease tension

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I've tried a lot of supplements over the years, but there are just a few that I cannot travel without. And one of them is Mitapur by Timeline. It contains urolithin A, a powerful compound that supports your mitochondria, the tiny power plants in your cells that drive energy, metabolism, and healthy aging. I take it as part of my Young Forever Longevity Shake. Why? Because it helps clear out old dysfunctional

mitochondria and helps your body build new, more efficient ones. That means better energy, better muscle function, better brain health, all the things that start to slow down as we age. And now Timeline has made it even easier to take with sugar-free strawberry gummies. Two a day gives you the full clinically effective dose. They taste great and they're part of my daily routine. Timeline is offering my listeners a special discount. Just go to timeline.com slash drheimann and give yourselves the support they deserve. Yeah, it was interesting to say that. I mean, I didn't want to double-click on that too because I was on a panel once at Cleveland Clinic with Stan Hazen, who's a

permanent cardiologist there who's studying the microbiome and cardiovascular health. And it's connected to cancer, to diabetes, to Alzheimer's, you name it, right? And maybe part of its way it's affecting it is through the mitochondria, who knows? But Stan Hazen said that a third to half of all the metabolites in your blood come from your microbiome.

And you're probably wondering, what is he talking about? What are you talking about, Dr. Hyman? Basically, when you have bacteria in your gut, come from your microbiome and you're probably wondering, what is he talking about? What are you talking about, Dr. Hyman? Basically, when you have bacteria in your gut, they have DNA and DNA's job is to make proteins. And you have probably 100 times as much bacterial DNA as your own DNA, because you've got a thousand species, they're all different, they all have different DNA, you know, we might have 20,000 genes, there might be two million

bacterial genes and each one of those genes is making protein. What happens to those proteins? Well, they're sometimes active in your gut, but they also get absorbed by your body. They get absorbed and they're in your blood. And then what are they doing there? Well, they're influencing everything. We're going to talk about what some of these things are. They're called postbiotics. Postbiotics are essentially different than pre-year probiotics. They're things that are made by bacteria that then are used by the body for different functions.

So we're gonna get into why we're here to talk about this, because I think the question is, if hermeticondria are so important, if they're so damaged by our current lifestyle, a poor diet, lack of exercise, stress, lack of good sleep, environmental toxins, lack of exercise, stress, lack of good sleep, environmental toxins, overload of calories and sugar, changes in our microbiome that actually are not good,

what can we do about it? And we hinted at a little bit about exercise, diet, supplements, and people should understand that the supplements around mitochondria are pretty well studied, and there's basically this chain called the respiratory chain, basically when you pour in food and auction

to one side of the factory assembly line, out the other side comes energy. And to get through to get to energy, there's a lot of steps. And all those steps require enzymes and all those enzymes require helpers. And all the helpers are vitamins and minerals or other compounds that are used by the body

like creatine or carnitine and so forth. There's ways of actually supplementing to optimize mitochondrial function and health. I use this in autism, I use this in cardiomyopathy, patients with heart failure very effectively, metabolic cardiology, now we have metabolic psychiatry. So in a way, when we say metabolic, what we're talking about actually is mitochondria

because that's where a lot of the metabolic function happens. Yeah, 200%. I think today we are in the midst of a metabolic crisis and I think the answer to a lot of that reversal and prevention lies in mitochondrial health and reversing the mitochondrial health of the population. And so whether it's neurodegeneration or whether it's, as you said, cardiovascular

incidence, I actually think, you know, and I started studying a lot of sarcopenia and frailty, older adults who can move well. And the fundamental thing that I always found was the poor mitochondrial health was uniform in somebody who can't get up properly from a chair, somebody who's super inflamed when they're in their 80s and 90s. And I think that sets in very early on. I believe that sets in even when these folks were 40 and 50. So that's the cumulative of the ignoring the diet and the physical activity and the stress

and this poor sleep or toxins. It's really 30, 40 or throughout our adult years, what we are seeing. So I actually think health span or mitochondrial health is something people need to think as a marathon, a longevity marathon that they think in their 30s and 40s, what can I do already? So when I'm in my 70s and 80s,

my mitochondria are enabling me to get up from a chair and cross the zebra line in 15 seconds, you know? So that's where I come from, that's how I started into mitochondrial health. Yeah, I mean, I think it's so important people have to kind of really get that, you know, if you want to really be upstream of all these diseases, you have to start thinking about mitochondrial health

and what caused mitochondrial harm and how to optimize mitochondrial function. And so, what is sort of a big myth or misconception you hear about things like energy, fatigue? Yeah, I think a lot of misconception I hear is that this is pretty much set in stone. It's irreversible. Oh, I hear now a lot of people who got post-COVID

fatigued who have this sort of what we are still struggling to define as what is that long COVID syndrome. They all are super fatigued and they think it's set in stone and they're struggling to find something. And I think there's a lack of research now, but I think all roads need to look into this whole seek-a-ly of poor mitochondrial health, because I think that's also a key element there. So I think general education about mitochondria, as you said, I mean, everybody just has this high school textbook knowledge.

I think what you said is important, and we didn't talk about it earlier, and we talked about the cause of mitochondrial dysfunction, but infections. When you have a virus, and you have have the flu and you feel exhausted and tired and achy, why is that? Because it's basically poisoning your mitochondria. And so that pass is usually and you recover, but, but it's,

it's an interesting phenomenon. So we sort of get a short-term acute mitochondrial dysfunction. Let's talk about solutions because, you know, we now have understood that these are critically important health and aging, that there's a lot of things that damage them, and we sort of hinted at some things like diet and exercise and supplementation that can help. Let's first talk about what are the natural ways that you can actually trigger mitochondrial renewal,

the making of new mitochondria, you mentioned biogenesis, which means just making new life, new mitochondria, and also mitophagy, which is just making new life, new mitochondria, and also mitophagy, which is cellular cleanup. So what are the natural triggers for these things? I think there are enough studies on exercise interventions.

That's the one I'm most familiar with. Any kind of exercise, just moving 8,000, 10,000 steps a day, just doing your resistance or endurance or a mix of both training has profound might these areas we talked about these are mitochondrial drug is exercise the best mitochondrial drug so just getting people moving in their 70s and 80s three times a week for 30 minutes that's that's the basic you know of having a rejuvenation effect on the mitochondria. The fact that we are unable to get people at that age to do that is a problem, I see, you know.

And that's why...and then diet, I mean, we talk... Before you jump there, in terms of exercise, what are the differential effects of strength training, resistance training, and cardiovascular training, like walking or biking or running or whatever? They all have been studied and they all have different impacts on mitochondrial improvements. Resistant training less so as something like high intensity training or aerobic training in terms of the impact on mitochondrial health. But any kind of movement I believe is good for mitochondria. So we just need to get people moving,

whether it's walking or just spinning in a yoga class for 30 minutes, I think that's very essential. Yeah, I mean, well, the way I think about it is that like cardiovascular fitness, particularly VO2 max training helps increase the efficiency and function of your mitochondria and may help you recruit new mitochondria, but also strength training increases the number, the mass, right? You get more muscle mass, you get more mitochondria and may help you recruit new mitochondria but also strength training increases

the number, the mass, right? You get more muscle mass, you get more mitochondria. So building muscle is really important. Muscle quality, I think that's another, you know, if you look at the entire sarcopenia field, whether it's. And what's sarcopenia? So sarcopenia is this age-related muscle disorder and so when we are in our 30s,

we peak in our muscle performance around a third decade of life. And following that, every 10 years, we're losing 10% of muscle strength and muscle mass. Okay? And that accelerates even bigger than 10% in our 60s. So by the time we are hitting our 60s and 70s, we have lost enough muscle mass and strength that a lot of individuals are classified if they can't get up from a chair or walk a certain

distance in six minutes and they're classified as sarcopenia. So it's really loss of muscle and strength and the quality of the muscle. Those aren't inevitable. I mean, I just had a major health crisis where I had a back surgery from a back infection. I lost 20 pounds, 15 pounds actually. And in the last four months, I've gained back 20 pounds of muscle, even at 65 years old.

Yeah, yeah. So, and I actually am more, quote, ripped now than I was at 40, because I didn't really do any strength training. And I think it's interesting to see how even as we get older, no matter how old we are, the body will respond to the- Muscle is a little sponge, you know? It just needs a little stimulus to get it going.

Then you're talking, we're gonna talk about diet. Well, of course, there's a lot of nutrients, right? So all the high protein we talked about, high protein supplementation as you age, there is this concept of anabolic resistance that after 60 70s if you keep doubling your protein And what people forget is that mitochondria is where a lot of protein synthesis is actually happening. So We're just doing a trial actually in Canada where we are combining high protein supplementation with a mitochondrial Intervention to see if we can rev up just that, you know, the muscle quality through that. So I

think diet itself, and you talked about less sugar, eating calorie restriction as intermittent fasting has these immense mitochondrial effects. So eating 15% less as we have seen in multiple randomized trials that has a big impact on boosting mitochondrial health. When you say protein, how much are we talking about here? Because the RDA is 0.8 grams per kilo, which is the minimum you need to prevent a deficiency of protein,

but not maximum amount you need for optimal health. Yeah, I think with aging, it should be up so about a one, 1.2 even, per grams of per kilogram. So the whole, most older adults are eating 40 grams less. So they that's why you know this idea oh you give them protein shakes with 10, 20 grams twice a day so you're countering that deficiency but they don't digest all these. It's not that you can give them a bolus of protein and they'll digest it because their body and their cells won't metabolize it. But I do and I look at my parents who are in their 80s,

they don't get enough protein from the diet. So that's a big problem today for most of us. So as you're older, you need more. And I think there's been work by the Proteage Group, Don Lehman we've had on the podcast talking about how as you get older, you might need to even up gram per pound of ideal body weight. So if you're 70 kilos, or let's say 150 pounds,

you need up to 130 to 150 pounds of grams of protein per day, which is more than most people eat, especially as you get older, it's really important. So I think it's important that protein, protein quality, it matters too, because if it's plant proteins, one, it's hard to get that much, because you're also carrying with a lot of starch, rice or beans, but if you use animal protein,

you're gonna get a much more concentrated protein at a lower calorie count, and also with higher levels of leucine, which is the amino acid you need to actually make muscle. And then there are nutrients like, the good fats like MCTs. I mean, just having your body in sort of a ketosis state, having more ketones.

Ketones, Bruce Palmer has done a lot of work in there and a lot of other groups. Eric Verdano, I collaborate, is looking at them. And just getting your body to more using fat as a source and sort of a carbohydrate, you know, glucose, has this profound effects on getting mitochondria wrapped up. They like processing towards the preference for fuel utilization is more fat than glucose. Yeah, so the mitochondria love to eat fat. And that's why you see, for example, certain diseases,

like whether it's autism or Alzheimer's or schizophrenia or bipolar disease or depression, diabetes. And these are all mitochondrial problems and they all respond extremely well to ketogenic diets. They respond better than any other current therapy. And I've seen kids with autism just to wake up and I'm going to keto diet or people with Alzheimer's or obviously with diabetics, we see with the data really strong on that, reversing type two diabetes. So having, you mentioned MC2L,

that's a particular kind of fat that's absorbed differently than other fats. It is a great fuel source for mitochondria. I'll use it actually before I work out or exercise, if I go for a long ride, bike ride or something. I'll often have some of that beforehand, and it'll really keep my endurance up and keep my metabolic function high.

And the last class of nutrients that I have, I'm very familiar with is these sort of antioxidants polyphenols. So all the berries, the pomegranates, the nuts, kind of, you know, it's kind of the Mediterranean diet. And that, if you look at, and again, studies have been done with folks who have been on Mediterranean diet and that, if you look at, and again, studies have been done with folks who have been on Mediterranean diet versus other diets

and showing how big an impact that has on mitochondrial health. So that's how, I think that's where people need to think about from a diet what to integrate into. So yeah, so from the diet perspective, more colorful plants, and I think I wanna get into one particular one, which is derived from a compound, one of these compounds called the logic acid

that's found in berries and nuts and pomegranate, which is a really important advance, I think, in terms of mitochondrial therapeutics, which I use regularly in my practice, something called Mitopyr, which is basically a compound called Urolithin A, which you're involved with and studying and Eric, one of the key researchers in this whole field.

So before we get into that, you know, we touched a little bit about supplements besides something like Urolithin A, like CoQ10, carnitine, creatine, and there are lipoic acid and acetylcysteine. There's a whole bunch of things that you can use to manage the energy production cycle, the B vitamins. So you need all these things. NAD is something we talk a lot about in terms of longevity and aging, which is a derivative of vitamin B3 or niacin,

but it's used by the body to make energy. So there's a lot of ways to actually soup up your mitochondria. What I wanna sort of get into is this discovery of this compound called urolithin A, which is one of those things we call the postbiotic. It's something that's made by gut bacteria

that then is absorbed and then it has biological function. Now most of us who've taken antibiotics, which is pretty much everybody, I mean, I gave a talk to about a thousand people the other day and I said, who here has not taken antibiotics ever in their life? I think it was like one person that raised their hand. That kind of wipes out some of the key species

that make this post-biotic. And you've actually concentrated it, purified it from plants, from pomegranate, and I don't know if other sources. What is this compound, what does it do, how does it work, what does the data show about its effectiveness? Start out with what it is and how it works, and let's talk about then what does it do to the body.

So this is a 15 years journey of research trying to discover why are pomegranates superfoods, right? So what we discovered was that, we initially thought it was these polyphenols, these elagitannins that are in the pomegranates that were responsible for all the health benefits. And so we started studying them. We started looking at the gut microbiome derivatives, which we thought were just byproducts and waste products of this metabolism. And we chanced upon this family of urolithins. Now the body can

either make in majority cases if you can produce urolithin A, but there are other urolithins you can make. So what we discovered was that this molecule, urolithin A, is actually not a waste product, it's actually a very potent gut metabolite produced by the gut microbiome that has these immense rejuvenation effects on mitochondria. And not everybody has the right gut microbiome, again, bringing the story that we were talking about in the gut microbiome before. Now, I've done studies where I've gone

in different parts of the world. So the Europeans have the highest number of producers. Yeah, so if you go to the French and the Italians, you find out of 100 people you sample, 40% will make. From the diet, naturally real world level, they will have some levels of urolithin A in their bloodstream. You go to the US and Canada, that number drops to 10%.

Wow. You go to my origin country, which is India, where every kid growing up in their first year is given antibiotics for everything, the incident drops to 5%. 5% in India? 5%. And I'm one of those that I can drink six glasses

of pomegranate juice or eat six bowls of walnuts and pecans. My body just refuses to make this molecule. So that's how we discovered this molecule. And then we started discovering its benefits. So the fact that majority of the adult healthy adult population doesn't make it means now you have a case to supplement most of the population with it. And then what is it actually doing?

What is it actually doing is what we started talking about is it revs up this cleaning up process. So it's really like a super Pac-Man molecule which takes the debris out from the damaged mitochondria and puts them into sort of more healthy status. And the data is showing that if you give it to different species, you get these immense improvements in muscle strength and endurance. Mostly the trials we run in placebo-controlled randomized trials, we see in the absence of exercise, in the absence of changing their diets, you get about a 10-12% improvement

in strength. You get about a 10% improvement in VO2 levels, so this aerobic endurance we talked about, and you also get lower inflammation. So that's the data. Well, that's just so mind blowing because you just said, I was gonna, again, double click on this. You're saying that you could take this compound

that's made by bacteria as a supplement and without ever getting up off the couch, just by taking this, you're gonna see about a 10% improvement in strength in cardiovascular fitness and a reduction in inflammation. It's not a magic pill, Mark. So what we do see is that it hits the same biology as what regular exercise would do.

So the same PGC-1 alpha. So a month in into taking orally the molecule and we have done studies where we have figured out the right doses that triggered this therapeutic sort of effects as well. So the first studies I did was I started giving, you know, increasing doses of this molecule to older adults who are sedentary. And I found a sweet spot around the 500mg to a gram dosing of this molecule, where a month in, no big physiological effects. But if I went in and took blood and biopsies,

I could see the damaged mitochondria turn and become into healthier mitochondria. There was more PG1 alpha. There was less damaged mitochondrial DNA. Two months in into supplementation is where I pick up things like physiological changes, so peak VO2 is improved, because now it's like mimicking the effects of intermittent fasting or regular exercise

hitting the same pathways. And then longer term, four months up, we start seeing these real long term benefits that I mentioned about, which is improvement in strength. So it's not like you just pop a few days and you- No, no, but over time, over a few months, it's basically like exercise and a pill. It is hitting the same pathways. And so that's the case, I always say,

it cannot replace exercise, it cannot replace good diet, but it can be this third pillar of this foundation of cellular health. And so that's really fascinating. And you publish a lot on this. I mean, there's many studies in major medical journals, including JAMA and other journals, Cell Reports Medicine. I've read these studies,

and they've been really compelling to me. And that's really why I take it every day. I mean, as an older guy, yeah, I want to get all the benefits I can. So I take a thousand milligrams a day of mitopur, urolithin A. And I've noticed it definitely does help my energy. It helps my exercise.

Really interesting. And I want to keep my muscle healthy as I get older. And there's not a lot of ways to sort of overcome the, this sort of accumulation of damaged mitochondria. So mitophagy is not an easy thing to induce, right? And so this is kind of a unique therapy in terms of that. With very little side effects.

It's a natural molecule, evolutionary, it's been present. Our ancestors probably all made it because they were hunting and eating from the farm and et cetera. What I do think this molecule is different from all the NAD boosters or CoQ10 or we talked about L-carnitin creating like molecules is those can only work if you take

the bad damaged zombie mitochondria out from the real estate, right? So if your cell, think of its cell as a town hall and it's all clogged up by bad damaged mitochondria, unless you clean the waste out, unless the waste removal truck shows up, which in this case is mitopure, that's where I think the future research will go

is how do you combine some of these nutrients together? You know, first you clean out the waste and then you can even potentiate the effects of things like NAD or creatine. And so that's the area of research we are now also building on. So essentially what you're saying is that, you know, some of these mitochondrial boosters,

like NAD or CoQ10 or carnitine or lipoic acid or other things that we'll use, work better if you clean up the old mitochondria. They work best on pretty good functioning mitochondria, but if you have damaged mitochondria, they just are sort of like dead weight. And that's what makes mitopure or urolithinase so unique is because it's one of the only molecules

that is really clinically shown to activate mitophagy, clean out the debris, and then potentiate the other probably the effects even of exercise. And these are studies at least we need to think about. Can you combine intermittent fasting with certain, you know, things like NAD or mitopure together and augment the effects? I think this is where I think research is going. In terms of inflammation, we chatted a little bit about before the podcast about this, this new kind of insight you've had around

the relationship between inflammation, which is one of the hallmarks of aging, and mitochondrial dysfunction. Can you kind of talk about the sort of bi-directional effects of inflammation and mitochondrial dysfunction? The early trials we did, as I mentioned, whether it was the older adults, you know, sitting on their couch potato, not getting to move,

or the overweight folks, or even the elite athletes, the hallmarks of whatever we would see improved mitochondrial health, in the background we will always see lowering of C-reactive protein. We would always see lowering of interleukin, one beta, or TNF-alpha. Those are cytokines.

These are cytokines that are, yeah, as you said, the zombie cells are spewing these cytokines out. And we started wondering, and I'm a trained immunologist, so I wondered and then we partnered with Professor Eric Cordon, who's a leading aging researcher and immunologist as well. And he said, well, let's do a trial where we give this molecule for a month to healthy 40, 50 year olds.

And we look at every single immune cell in the body at the impact it's causing and the mitochondria in it. Now, this has not really been done with any other nutrients or even exercise for that matter. So we started doing, we did this trial and then Eric Scripp ran a whole scan of 80 plus immune populations. These are, you know, these are as an immunologist, you talk about different kind of T cells. The T cells are these cells in your body that fight infections. And then you can also profile things like NK cells, which are called natural killer cells. As we age, the number of these immune cells declines in our bodies. And that's why you get sick more, you don't respond very well to vaccines, etc. What we actually now find with supplementation is that a lot of these immune cells that are declining with aging, they come back with mitopure supplementation.

And when they come back, they have more mitochondria, just like what we were seeing with the skeletal muscle or what other groups have shown with the neuron cells. And these immune cells are more wired to fight infections. So if you throw an infection on them, they engulf it and kill it much faster. To me, this is probably, and hopefully it gets published very soon, but I think it's one of the breakthrough findings connecting our immune health and the declining immune health. I think now I'm changing my mindset that that's actually the first hallmark that sets in in our bodies is the declining of immune aging and the immune fitness and then all these other hallmarks start to percolate around it and gradually. So this is the latest research we have. That's interesting. So essentially what

you're saying is that with this compound which affects mitochondrial health, that by improving mitochondrial health you improve your immune health. Which is a fascinating concept that you can take. And so now what we are looking at is the trials, the randomized studies we are even thinking is can we actually give it to even people who have beaten cancer, for example, who have taken a lot of chemo, their immune cells are damaged because chemo radio damages every, even the good cells. And can we bring the immune system back? Because a lot of these cancer patients who recover from cancer, they, you know,

they have one low fatigue and low, they have muscle wasting, but the number two reason is that they have a lot of infections because the immune system goes for a toss. So can we bring their immune system back and rejuvenate it much faster? So the number of ideas we have is how to use mitochondrial medicine to rejuvenate the immune health. It's really mitochondrial rejuvenation and also immune rejuvenation. Yes. Which is something we don't really think about in medicine and it's sort of the immune rejuvenation, which is something we don't really think about in medicine. And it's sort of the opposite of how we practice medicine.

We use compounds or drugs that inhibit or block or interfere with some biological process, like an antihypertensive or an antibiotic or a calcium channel blocker or an ACE inhibitor. So we're inhibiting, blocking, and antiing everything. These are doing the opposite. They're actually enhancing health. They're optimizing function. They're actually enhancing health.

They're optimizing function. They're rejuvenating different biological systems that are critical for health and longevity. And when you look at chronic disease as a whole, and we talked about everything from schizophrenia to autism to Alzheimer's to diabetes, cancer, these are all mitochondrial immune issues. They're all kind of the same at the root.

Alzheimer's, I mean,'s is a classic example. For many years it was a proteostatic disease, with all these accumulation of molybdenum plaques and the lack of proteostasis. Now it's turned around. It's really an inflammatory disease of the microglial cells. And that's where I think a lot of aging diseases need to be reversed or early on

by tackling inflammation in mitochondrial health. In sort of the whole space of longevity, there's a lot of compounds that people are talking about, looking at, and some of them are, some of them have good data, some of them are questionable. You mentioned metformin. This is something that works on a similar pathway,

but one of the consequences of metformin is that it inhibits mitochondrial complex one, which while, well, it seems like it helps with blood sugar and many things you'd want to have it help with. It also interferes with mitochondrial function, which worries me particularly. Right? No, it is. So there's near near Balzai has been studying metformin for a long time and now he has this big trial. I believe the TAME trial, looking at the long-term effects. I think that got canceled. Yeah, okay. They couldn't get the funding for it because it wasn't a

patentable drug. So that's the challenge, right? Or you look at rapamycin which has, as you were talking about, mTOR inhibition effects, but rapamycin was basically serolemus, an immune-suppressive drug. So again, what is the impacts on immune health is unknown. So that's where I feel the longevity field today needs to have a more 360 approach where they sort of look at compounds that affect the key organs. And so the three, and I talked about it.

So there is this, I don't know if you know about the XPRIZE initiative. So XPRIZE has this healthspan prize, longevity prize, and they're looking for compounds or intervention strategies that hit or can improve ten years, lower ten years healthspan increase on muscle, immune and brain. Because those three organs, I think, together, if you can hit on all three of them with one intervention or a multiple, I think, together, if you can hit on all three of them with one intervention or multiple, I mean, there's no magic bullet in this case for, but I do think urethra and mitopur comes close.

And so now we are now looking at the third one, which we don't have much data, which is brain health. So that's where we're going into this. Looking in the next frontier in research for mitopur is looking at brain health. Yeah. That's a good idea because I think it's, you know, it could really enhance a lot of mitochondrial brain disorders,

everything from Parkinson's to Alzheimer's to autism to depression to bipolar disease, to schizophrenia that the brain is, you know, again, has the most density of mitochondria of any organ in the body. And so it makes sense that by regulating those and rejuvenating your mitochondria in your brain, you're gonna do better. One of the things that we also talk about is improvement in the cardiovascular biomarkers

with urolithin A and heart health. Can you talk about its role in heart health? Yeah, so we just published a paper in EyeScience. And so this was again in models. So this is not a randomized clinical trial, but these were models of heart failure. So the first thing our group of very brilliant mitochondrial scientists did is they actually looked at

cardiac biopsies of people who had heart failure or had died of heart degeneration with the aging process. And again, the signature, the hallmark signature they picked up in the heart was poor mitochondrial health. And so then we went into models of heart failure, acute and chronic, and we found that giving mitopure supplementation in these models reversed a lot of this cardiac damage by improving mitochondrial health. And in the human trials, we haven't done a trial in heart failure, for example, but in older adults, for example, we have focused on a class of molecules called the ceramides. Now ceramides, if your heart cells are not performing

well, you accumulate a lot of these ceramides that are like mitochondrial toxins essentially. And so what we see is actually in all our trials, ceramide plasma levels of ceramides are going down. And so there's the Mayo Clinic that has now a score of ceramides that allows you to predict the prognosis of cardiovascular health. So now we are looking in that direction of how we can look at long-term cardiovascular health. So now we are looking in that direction of how we can look at long-term cardiovascular health. But we do know things like VO2 improve with mitopure, which is also cardiovascular health. So I think we just need to put,

you know, research is two words, reinsert. So every small step you have to keep building on the journey. Right, right, that's true. Reinsertion, I never thought of that. There's a whole field like now of metabolic psychiatry, but there's also a field of metabolic cardiology, which has not really been part of traditional cardiology. There's a cardiologist named Steven Sinatra, who is an old school nutritional

doctor who I knew and who I know was quite amazing. And he taught me a lot about metabolic cardiology. So when I have heart failure patients, I will give them a mitochondrial cocktail of supplements, including CoQ10, carnitine, creatine, ribose, lipoic acid, n-acetylcysteine, the B vitamins. And basically what happens is quite remarkable. They prove their cardiac function by objective metrics like what we call ejection fraction,

which is how much your heart can pump out with each pump of blood and each beat. That's a direct measure of how well your heart's functioning. And so I'd be very curious about looking at ejection fractions and urolithin A and how that works, but you can't really just do one thing. People are like, oh, I'm just gonna take this medicine or this supplement and I'm not gonna exercise or eat well.

Because you're eating a lot of sugar and you're not exercising, you might get some benefit, but not really. So you gotta combine it with everything else in a healthy lifestyle. What about skin health? Because we don't tend to think about mitochondria and skin health, but might appear

to produce a lot of skin products, which I found very interesting. You know, about three, four years back when we, and sometimes you have to listen to the consumer, when we launched these products, of years back when we, and sometimes you have to listen to the consumer, when we launched these products, of course people said, oh, I have more energy, I have more strength, but the number one feedback that we did not expect to hear

was people started coming to us and telling, hey, my partner just told me your skin is glowing and looks better. And as a scientist, you take it in a pinch of salt, you say, ah, that's an anecdotal feedback. But we said, okay, let's look at skin cells between a 30-year-old, a 50-year-old, and a 70-year-old and see if mitochondria are actually damaged in the skin cells.

And the answer was yes. The answer is that the skin cells in the fibroblasts or the curtainocytes, these are the two main cells in the fibroblasts or the curtainocytes, these are the two main cells in the epidermis and the dermis, they have lots of mitochondria and over aging, over time of adult health span, they get damaged in much the same way as muscle and brain cells do. And so we made these topical formulations with Mitopur and applied it in randomized trials in middle-age, older-age volunteers.

And lo and behold, when we did the skin biopsies, the mitochondria health started turning. And when mitochondria health turned and improved, suddenly you had things like collagen pathways. These are, you know, collagen is the protein that keeps your skin together, and there are enzymes called matrix metalloproteinases, MMPs, that degrade collagen, that just shoot up with aging. And what we saw in these trials was that MMP levels were going down. And so-

That's a marker of inflammation. That's a marker of inflammation, that's also a marker of how much collagen you're going to degrade. And so we then started, of course, you have to do the standard imaging and looking at things like wrinkles and hydration. And we saw all these markers improved over time, again, not instantly, but over time. So there is this now great appreciation of that mitochondria in the skin. And skin is this, one of the organs that is receiving the most external insult from, whether it's harmful sun rays or pollution, et cetera. So it's under so much stress in addition to the intrinsic

decline in mitochondria, it's also receiving this. So that's where we now see some great data that we're getting ready to publish, but the products are a big hit, with the topical products with mito. People are loving it. In the skincare business, not many people actually even bother doing clinical studies,

so that's where, as a science-driven company, we have taken the call. Yeah, I mean, that's really unusual. I mean, just to sort of highlight for everybody listening, most health companies don't spend millions and millions of dollars on clinical research, which you guys have done the call. Yeah, I mean that's really unusual. I mean, just to sort of highlight for everybody listening, most supplement companies don't spend millions and millions of dollars on clinical research, which you guys have done. Yeah, and I think it's really changing

how supplementation should be seen as really a technology, much like people think about biotechs in any tech company. I think that if you bring the evidence on the table, like people think about biotechs and any tech company. I think that if you bring the evidence on the table, people will buy and get convinced. And that's where I think the dietary supplement world is ripe for disruption.

It's true, it's amazing. And I think we're gonna link to all these studies that we've talked about in the show notes. So there's plenty of peer review, randomized trials that you guys have done that are in major journals that have kinda convinced me by looking at the data, and it's not a panacea, but we need all the help we can get at this point

given the amount of insults or mitochondria from our diet, from lack of exercise, from stress, poor sleep, from toxins, from infections, from our microbiome, I mean all these things just kinda burden us, and we really haven't had a way of really treating mitochondria very well before. I mean, there's been some supplements you can use in lifestyle, but this is sort of a novel advance.

Just in terms of practical applications, where do you think the science is heading in addition? You mentioned a few things like the skin health, and you mentioned the immune health. What else are you thinking about? Higher level mitochondrial science is going to different ways where, as I mentioned now, they're trying to integrate all these other hallmarks

of aging and how they link to mitochondrial health. But more important, the holy grail is to find a constellation of biomarkers clinicians can measure in clinic, which is not yet available. You know, clinicians are not saying, oh, let me tell you how good your mitochondrial score is or mitochondrial health. So I think that's coming. What are those biomarkers? These are biomarkers where you're looking at the performance of a mitochondria, whether you're getting through a buckle swab.

the performance of a mitochondria, whether you're getting through a buckle swab. So again, you talked about it, the different complex activities, mitochondria like a factory, as you mentioned, so complex one, two, three, four, five, you can profile them and their performance in the activity. And you can also look at mitochondrial DNA and the damage in the mitochondrial DNA.

So this requires complex genetic technology sometimes. So I think it's still a further way. But I believe companies like MeScreen have some good technologies where they can take blood draws and tell you how good your mitochondria and your blood cells are. And integration in terms of urolithin A, the real cool research I think will come out

is this immune story we talked about, but the frontier of how it can impact cognition and cognitive health and health span in general. So I'm happy to share that we actually were one of the X Prize winners on our research that will be announced in a couple of weeks. You won the X Prize on? On the health span, we are one of them, one of the top finalists. Oh, announced in a couple of weeks. You won the X prize on? On the health span.

We are one of them, one of the top finalists. Oh, you're a top finalist. And the whole reason the whole- You haven't actually won the prize yet. Not the big prize, but we are one of the finalists that gets the first prize, and then we compete with the other top guys for the $80 million prize.

So that's a recognition of the research we've put on muscle and immune, but I think the brain is what will take us to the next level. That's incredible, the brain, final frontier. Because the brain mitochondrial connection and the dysfunction in there does cause a lot of suffering. From neurodegenerative diseases, to neurodevelopmental issues, to mood issues, right?

Absolutely. This is important. Sleep, yeah, as well. Sleep. Yeah, I definitely think there's a mitochondrial connection to sleep. I think that's true. One of the things we didn't talk a little bit more about, I think, is some of the diagnostics. And I've been using some of the diagnostics in buckle swabs

and organic gas testing for a long time. There's some newer tests out of Europe I'm curious to share with you that I think are really fascinating. The Mi screen is looking at blood work that you can do at home. It's a home test, right? And we're gonna put the link to that to mescreen.com.

What are they actually measuring when they look at that? They're measuring how the stress to your mitochondria, they look at a constellation of mitochondria readouts. So can. Or free radicals. Free radicals. They are looking at complex one and complex two activity inside the mitochondria. They are also looking at the respiration, how good and bad the oxygen consumption is at a mitochondrial level. So that's what they're looking at.

And they're looking at the oxygen consumption at the level of the mitochondria. And they're looking at the respiration, how good and bad the oxygen consumption is at a mitochondrial level. So that's what they're, and then they look at all these and they give you a mitochondrial score and sort of a holistic mitochondrial health score. Important, yeah, because I think being able to measure it and what's happening is important

because we wanna look at your mitochondria and you wanna see the effect of any interventions you want to know what you're doing and again it's not something we've really thought of focused on in medicine. There is one mitochondrial story I want to I want you to kind of finish up by telling which I think is important which is what I think one of the greatest mitochondrial toxins and also something that is incredibly widespread use. It's a medication that's commonly prescribed the most common medication prescribed in the world, which is?

Statins. Statins, right. So cholesterol medication. Tell us why these medications are harmful to mitochondria, what they do, and if we should really be worried about it. At a higher level, there are mitochondrial toxins and they deplete these sort of electron transport chain and CoQ10 deficiency happens.

And so a lot of trials have looked at how you can resupplement with CoQ10 and recover some of the damage caused by statins. They are also muscle toxins. So a lot of times you will see people with statins, they come to you with muscle pain and things like, in the extreme cases, rhabdomyolysis, which is really, you know, disintegration of the muscle.

We haven't done anything with nutritional interventions on statins, but I think the body of evidence is that they really are damaging to the mitochondrial network and the electron transport chain. And CoQ10 levels are very low in all those who get statins. Yeah, because the same pathway that makes your LDL cholesterol also makes coenzyme Q10, which is one of the mitochondrial helpers, cofactors.

And so you're kind of screwing yourself. So anybody who's on a satin has to be on Coenzyme Q10. The question is, does it mitigate the damage or not? To a certain level, I believe it does, but CoQ10 is not also very highly bi-available compound and taken orally. And so there have been attempts at making liposomal CoQ10 and things like this to make it, you know.

But I do think something like either NAD supplementation or cleaning out the waste with Mitopur could go a long way. And this is something we thought about long back, but doing a trial with a drug and a supplement always, you know, when you go to an institutional review board for a clinical approval as a first study, they see it as a drug trial. And so that's always the risk of doing that trial.

That's why we haven't done it. Yeah, but I think it's important. And I think, you know, I do worry about it because some of the studies I've seen is even without any muscle pain, even without an abnormal blood test, which you can see damage to the muscle called CPK, that pretty much everybody on a statin,

if you do a muscle biopsy, has damaged mitochondria. It's not like some people, like almost everybody. And that to me is very worrisome considering the importance of mitochondria, particularly as we age, right? Yeah, and we are starting to see a little bit of that also with the steroids also. If you throw steroids on muscle cells, we have seen that,

that they have a very sort of detrimental impact. You mean prednisones, corticosteroids, not like testosterone. No, no, no, yeah, more like cardiosteroids. And again, there's this buzz with the GLP-1 story, that you lose muscle, so what's happening at the, it's almost like you're fasting, but you're not just fasting, you're not eating anything, right?

And that has a stressor to mitochondria. So I think you will see a lot of mitochondrial research come out with these GLP-1 drugs. That they're bad for them. Potentially, but the research needs to show that. That's concerning. That's concerning because they're, you know, getting used for everything everywhere all the time. We covered a lot of this,

but I wanna sort of bring it home a little bit and conclude by talking about some of the science-based evidence approach to longevity and to how people can support their mitochondria and think about their mitochondria. So testing is coming, we will learn more objectively what's going on, but in the meantime,

we kind of touched on some of these things. Would you summarize sort of a healthy mitochondrial lifestyle and supplementation program? Well, there's a, so I would say five strategies that come to the top of my head. So eat well, eat a lot, eat your berries, eat your fiber, eat your, you know, whole foods. I think that's the key.

And low sugar. Low sugar, yeah, exactly. Try to cut down. Good fats. Yeah, good fats, that's the key. And low sugar. Low sugar. Yeah, exactly. Try to cut down. Yeah, good fats. That's the key. Then keep moving, right? So make sure you walk, just not sit in the office all day. And that's the end.

Your muscles, your brain cells need to have that stimulus of exercise. Sleep well. I think sleep, I truly believe that a lot of research will come out in the next five years on how sleep regulates everything from metabolism to mitochondria. I see nutritional and I see advanced nutritional strategies which we talked about whether it's creatine, NAD supplementation, vitamin, the B vitamins, they are all great, you know, vitamin D, we didn't talk about that,

but it also has some great effects on mitochondria and immune cells. And then I think Mitopur fits in the ensemble, not in isolation, but in the ensemble. And I think the last bit on mitochondria, as you mentioned, is make sure you're not taking a lot of these toxins like drugs, we talked about antibiotics, we talked about statins. Make sure you do the consult your doctor and you know,

have a sort of 360 holistic view of how you approach mitochondria. I think that's a, that's very sound, good advice. The one thing I didn't think about, but I just thought about it as we're discussing this and you mentioned antibiotics one, because it affects your microbiome and your ability to naturally make your the one thing I didn't think about, but I just thought about it as we were discussing this, and you mentioned antibiotics. One, because it affects your microbiome and your ability to naturally make your L-L-L-L-L-L-L-A. But two, mitochondria historically came from bacteria.

So they're basically a symbiotic relationship with bacteria and humans, and they're not the same in terms of their DNA. They're actually quite different than your DNA. They're, you're comfortable with your mother, but it's mitochondrial DNA. And the question is, do antibiotics hurt mitochondria because they're basically come from bacteria?

There's certainly stressors. There's enough studies showing they're mitochondrial stressors. Now, I think it really depends on the duration of usage, the dose and certain class of antibiotics, they're probably worse off than the others. I think research is really lacking in that one. Yeah, nobody wants to look at it.

Nobody wants to look at it. But I think the last tragedy that a lot of people don't talk about is these holistic strategies, sauna. There's a lot of good evidence in sauna for mitochondria. Saunas. Yeah, saunas in near infrared, the red light therapies. So I think this parallel sort of,

I wanna say more medical diagnostic or more electroceutical if I can call it strategy, but these are also something that can potentially augment a lot of these other benefits in mitochondria. And research needs to come on that. I think that's where another under-researched area. That's amazing. Light therapy, other ways to enhance mitochondrial function.

There's also hypoxic therapies where you get low oxygen states or hyperbaric chambers which get high oxygen states. All these can be interesting mitochondrial therapies. There's a great research coming out from one of our collaborators who just co-discovered Urolithin with us, where he's seeing that living in cold rooms

or colder areas is better for your mitochondria than living in hot climates and tropical areas. So I'm coming from India, I'm not so excited, but this is the way research is gonna go. Fascinating, fascinating. So what is the most exciting that's coming down the pike in terms of the research frontier?

Personally, for me, I think it's the immune link, how we can reverse a lot of this immune aging with this simple mitochondrial tools. 20 years back when I was training as a physician immunologist, I didn't think that medicine would bring me to a place where suddenly by reversing your immune health, you can do that with the mitochondrial nutrient. So I find that for me, all my training is coming

to the right place in terms. And I think in terms of the whole longevity field, it's the awareness and building around the biomarker approach, you know, integrating things like intermittent fasting, things integrating nutritional supplementation. So I think that's more, longevity clinics are sprouting everywhere.

We can see that. People are more aware that this is not just a buzzword. So I think, as I say, to end with, this longevity is a marathon. Start today. That's incredible. Well, thank you so much, Dr. Singh, for being on the podcast and for enlightening us

with all the work you've done on mitochondrial health, how critical it is for just general overall wellbeing and also longevity and the work you've done to pioneer the research on urethane. It's not easy to do that work. It's hard, tedious work sometimes, but the results are pretty exciting. And I think we're going to look forward to hearing more and more over time about how this can apply to a broad range of problems from cardiovascular health to immune health, the longevity.

So everybody, we're going to put in the show notes links to how to immune health, the longevity. So, uh, everybody we're going to, we're going to put in the show notes, uh, links to how to find more about, uh, the research that we talked about around your LF&A links to the product itself. Timeline nutrition's might appear, which comes in many forms. It comes in powder or pills and now gummies, which are yummy. And, um, we're going to also, um, you gonna also talk about in the show notes, some of the sort of suggestions that we talked about around mitochondrial health and renewal.

So thank you again for being on the podcast and hopefully we'll keep having this conversation and learning more as time goes on. Thanks for having me. Absolute pleasure, Mark. Don't forget, there's a way to listen completely ad free. With Hymen Plus on Apple podcasts, you can enjoy every episode without any breaks.

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