Longevity MASTERCLASS: Biological Age, Mitochondrial Repair & The Superhuman Protocol

Ben Greenfield

My name is Ben Greenfield, and on this episode of the Boundless Life podcast,

Gary Brecka

if I was to boil my entire career down to one sentence, it would be that the presence of oxygen is the absence of disease. We did not find a single disease etiological pathway that did not either have its roots in the absence of blood oxygen or was not severely exacerbated by the absence of blood oxygen.

Ben Greenfield

Give me an example.

Gary Brecka

All cancer begins in a hypoxic environment. Sitting is the new smoking. But why is sedentary lifestyle, and why is sitting become the new smoking? Because sedentary lifestyle is a foundation for hypoxia.

Ben Greenfield

Welcome to the Boundless Life with me, your host Ben Greenfield. I'm a personal trainer, exercise physiologist, and nutritionist, and I'm passionate about helping you discover unparalleled levels of health, fitness, longevity, and beyond. In this episode of the Boundless Life podcast, I've got a mortality prediction expert, a molecular biologist, and an engineer who's been beating billionaires at their own game. Gary Brecka, a human biologist who spent 20 years in the insurance world predicting when people would die based on their blood work, and now he uses those same strategies or biomarkers to help people extend life and live a fuller life. Instead, I also talk with Dr. Anurag Singh, a physician scientist and trained immunologist with more than 50 published papers, 20 patents, and 50 randomized clinical trials behind him. He'll talk about the 15 years he spent on one molecule and what that one molecule does to your mitochondria, and then I've got Dave Pascoe, 61-year-old engineer who's near the top of the Rejuvenation Olympics leaderboard, out aging tech billionaires without their budgets, and he publishes his entire protocol publicly. It's not what you'd expect. All of the show notes are going to be at bengreenfieldlife.com/ultimatelongevity. That's BenGreenfieldLife.com/UltimateLongevity. Enjoy. I would love to hear a little bit more about what got you interested in this because before I came to Miami, you and I talked on the phone, and I always thought you were just some biohacker who was interested in the body, and you know, eventually took all the things you learned and started to do with other people, but you had a very interesting start. You were in like insurance adjusting or something. A very

Gary Brecka

specific area of insurance, which was the science and the predictability of mortality. It's called probabilistic mortality modeling.

Ben Greenfield

Okay,

Gary Brecka

so you know, if we got five years of medical records on you and five years of demographic data, we could tell the insurance company how long you had to live to the month. You see, because the database to the

Ben Greenfield

month to the

Gary Brecka

month. This

Ben Greenfield

wasn't like methylation clocks and Horvath aging and telomeres. This was just looking at epidemiological data.

Gary Brecka

Epidemiological data, but the one thing you have to remember that insurance companies have that no other clinical study has, no other medical enterprise has, no other published trial has, no medical enterprise of any type has, is that they know the day, the date, the time, the location, and the cause of death for everyone that they've issued an annuity, a life insurance, or or a reinsurance policy on, even a reverse mortgage, you wouldn't believe the number of financial services products that are actually based on how many more months you have left on Earth, and so when you have the endpoint, you can trace it back to causality. You see, in a clinical study, we know that, for example, obesity shortens your lifespan by X number of years. You know, type two diabetes shortens your lifespan by X number of years. This all data that's used on actuarial tables. How do we put somebody on an actuarial table? But when you talk about specific mortality, they have 10s of millions of deaths, and they trace that endpoint back to its causality. If this database could see the light of day, it would permanently change the face of humanity. It would upend modern medicine in a way that would absolutely be catastrophic. That information is like private. The insurance companies are the polar opposite of Google and Facebook. They collect voluminous amounts of information, but they don't share it with anybody. They use it to price financial service products against you. I mean, think about it. If they're going to take out a $25 million or $50 million life insurance policy on your life, like

Ben Greenfield

we're talking like a term life insurance policy,

Gary Brecka

we're usually talking about universal life policies that are going to last until the day that you that you die, right? So they don't expire after 10 years or 20. They're trying to

Ben Greenfield

predict when that data is going to occur, so that they don't get stuck with the bill.

Gary Brecka

Exactly, but if you think about it, they're taking 25 million or $50 million worth of risk on one variable. There's only a single variable that matters, and that's. How many more months do you have left on Earth? How many more months are they going to predict, or that they're going to collect that premium?

Ben Greenfield

Okay, and you're working for one of these companies.

Gary Brecka

I was actually working for multiple companies, so we did life expectancies, and we did these probabilistic models to basically take a portfolio of life insurance that

Ben Greenfield

one

Gary Brecka

life insurance company was going to acquire, and let them know if the mortality predictions were accurate or not.

Ben Greenfield

Okay,

Gary Brecka

because think about it: if you're if you put $25 million worth of risk on somebody's life, and you don't collect enough premiums to offset that risk because your mortality prediction was wrong, shitty business model. It's kind of a really shitty business model, and if you want to know how accurate they are, just look at the last financial services crisis. We had 364 banks failed. Not a single life insurance company failed. Not one.

Ben Greenfield

Really?

Gary Brecka

Not a single life insurance company failed. This how accurate and well reserved they are because they have perfected the science of mortality.

Ben Greenfield

So, what'd you find out?

Gary Brecka

If I was to boil my entire career down to one sentence, I say this all the time, it would be that the presence of oxygen is the absence of disease.

Ben Greenfield

Presence of oxygen is the absence of disease. Yes, we didn't.

Gary Brecka

We did not find a single disease etiological pathway that did not either have its roots in the absence of blood oxygen or was not severely exacerbated by the absence of blood oxygen. Can you

Ben Greenfield

give me an example?

Gary Brecka

Hypoxia. You know, all cancer begins in a hypoxic environment. Type two diabetes begins in a hypoxic environment. The

Ben Greenfield

Warburg effect: cancer generating energy anaerobically producing lactic acid tissue acidosis, and then springing

Gary Brecka

upon you to create that angiogenic effect.

Ben Greenfield

Okay,

Gary Brecka

to eventually provide oxygen to grow a tumor, but the genesis of that tumor begins in hypoxia. Okay, I mean, how does cancer decide where it's going to metastasize to? It looks for a focal area of hypoxia and it sets up shop in that area.

Ben Greenfield

Okay,

Gary Brecka

and if you look at anemia or sedentary lifestyle, these are leading causes of all cause mortality. Sitting is the new smoking, but why is sedentary lifestyle and why is sitting become the new smoking? Because sedentary lifestyle is a foundation for hypoxia. The less we move, the less we breathe, the more poorly we manage oxygen. Not only the faster we're accelerating towards the grave, but the faster the parabolic curve of all-cause mortality. So we could predict the onset of and the severity of disease based on your hypoxic condition. If you have anemia, for example, and it's non-responsive because you have the MTHFR gene mutation. You don't respond to folic acid. You only respond to methylfolate, for example, and you have a cardiovascular condition, atherosclerosis, arteriosclerosis. You can predict how much more quickly that will accelerate based on a normal table of atherosclerotic progression.

Ben Greenfield

Okay, and I know if I'm wondering this, other people might be also, but of course we seek out in some cases as health enthusiasts hypoxia, like you and I when we were doing the breath work out in the porch, like we got to certain sections where we were blowing all of our air out and holding that for as long as possible, or some people will do. I don't know if you've ever been like a CVAC chamber, which is hypoxic. Or I even do like you do exercise with oxygen therapy, but I have a little switch on that therapy device I use that pulls me into hypoxia, gets my polsto two down, like my blood oxygenation down, and then it goes back up when once I get that surge of oxygen. But you're not saying that all hypoxia is bad, right? No, there's a kind of like a hormetic effect to having periods of time with low oxygen. No,

Gary Brecka

systemic hypoxia is. Okay, long duration hypoxia is bad. Short term exposure to hypoxic conditions or even altitude can actually improve oxygen transport. If you look at the way that a healthy body responds to a hypoxic condition, it increases erythropoiesis, right? So that increase in erythropoiesis offsets altitude, right? But if you weren't weren't offsetting that altitude, and you put yourself in a hypoxic environment, your body didn't offset that oxygen deficit. You would have severe long-term consequences for that.

Ben Greenfield

Now, besides a hypoxic state, and this might be a loaded question, I don't know. But I'm sorry. Besides a sedentary state, like you alluded to with the sitting as the new smoking, what type of other factors have you identified that seem to be pretty associated with people being in this hypoxic state,

Gary Brecka

anemic conditions, age-related sarcopenia that actually collapses the respiratory rate and the respiratory volume, muscle

Ben Greenfield

loss and muscle inability to carry oxygen, lack of muscle. Yes. Okay.

Gary Brecka

Lack of I mean, muscle is our metabolic currency. Yeah. I mean, there's a direct correlation between early onset disease and even early onset death. And and your your muscle volume, the percentage of muscle that you have. I mean, muscle really is our metabolic currency. We're realizing now that muscle is more important in older ages.

Ben Greenfield

Now, I want to learn a little bit more because I'm intrigued about where you got to where you're at now with this whole 10x health, and you're probably aware of this. You're kind of blown up. Like I've been seeing you all over the place. What you're doing is obviously working, or you're paying the right people the right amounts of money. I'm just kidding. I'm I'm just kidding. And and so the question I have for you, though, kind of like back to the science of the hypoxia thing, and back to the light, and what you were explaining about with the light, the importance of first light, the importance of natural spectrum sunlight. If you would have walked into my room this morning, I'm increasingly becoming like this. Like I'm like a red light addict, right?

Gary Brecka

So

Ben Greenfield

I travel with a red light headlamp, and that's the only way I use to get around the house during the day or during the morning, right? So it's all red light plus my red light glasses, right? So my body's just basically bathed in sunrise, even if at a hotel or I got to walk down to the lobby to get a coffee or whatever. It's all red light for like the first hour of the day before I hit the big lights. You know, because typically I'm up around five or so. So my reasoning is, until the sun actually comes up, I want to keep fooling my body that we're in no sun or sunrise. And then I showed you that wrap around red light thing that I have. I forget the name. It's Kinion is the name of the company that makes it. I wrap that around my neck, right? And this the first hour after I'm getting up. So all of the blood going through my neck and my carotid is getting blasted with red light. And then I have a little travel-based red light that people have probably seen. Like Juve makes one called the Go. I have one that Doctor John Laurents gave me last week. That's got the little red, and so it basically is like putting the sunrise on in your bedroom. And so I'm all red light for that first hour of the day. Now these are all technologies. We'll talk more about some of the cool technology up here, like some full red light. Huge fan of

Gary Brecka

technology.

Ben Greenfield

So for this concept of first light, do you think that there's an advantage to that I'm still getting benefit from that versus what we did this morning and going out in full spectrum sunlight and sitting on your balcony? Do you use these red light devices when you first wake up?

Gary Brecka

I do. I you know I do the first light. I do the walk in the morning, and I believe in doing weights when I'm fed, so I usually do weight workouts later in the afternoon,

Ben Greenfield

which we're going to go do after this. We'll be we'll be crushing the weights podcast, so I go crush

Gary Brecka

it. But then I get back and I do what's called the superhuman protocol, which is essentially taking all of the good things from the outside and bringing it in. I believe we get three major things from Mother Nature, we get magnetism, we get oxygen, we get light.

Ben Greenfield

Magnetism, oxygen, and light.

Gary Brecka

Those are the three big things we get from Mother Nature. And the further we get away from those three things, the faster the onset of all cause mortality.

Ben Greenfield

It kind of begs the question, real quick. Sorry to interrupt.

Gary Brecka

No, it's okay. But

Ben Greenfield

when you say magnetism, oxygen, and light, and you found in these insurance actuarials that hypoxia was one of the big issues associated with mortality. Do you think that magnetism and light should have been on that list as well, or are magnetism and light kind of like the precursors to oxygenation?

Gary Brecka

They're they're precursors to oxygenation because if you think about how oxygen's transported in the body, and then the delivery system not only just to the cell wall, but into the mitochondria, which actually occurs more through the water, mitochondrial water, than it does through direct oxygen entering the mitochondria. But, but if you look at the degradation of the oxidative state of the body, right? A lot of this has to do with the charge, the polarity on the surface of the cell. Okay, and not to get too technical, but if you look at a red blood cell, okay. So let's get technical for a second. So if you look at a red blood cell, and we're going to do some dark field microscopy here after after this, if you look at a red blood cell and the surface of that cell has a charge, and just like a magnet, if if two cells have similar charges, they repel. If they have opposite charges, they attract. It's a you know pH stands for potential hydrogen. This a charge, right? That's why it's a complete fallacy that we can get alkaline from drinking alkaline water. We get alkaline by changing the charge of the body through low gauss current, through grounding, through earthing. I mean, discharging into the earth or discharging through a PEMF mat, low gauss PEMF mat, is the safest and the most natural and the fastest way to alkalize, repolarize the charge of the cellular structures in the body. I

Ben Greenfield

never really thought about this. So you're you're basically making the case that alkalization is synonymous with or linked to repolarization.

Gary Brecka

No question, it's linked to potential hydrogen. That's pH. The scale of pH is based on the potential of hydrogen. So what this means is, let's say you have a group of red blood cells and they're all hanging out in the bloodstream together, and they have similar charges, and they will repel. They'll slide around like like hard-boiled eggs, like

Ben Greenfield

protons with a positive

Gary Brecka

charge, like protons with a positive charge. So what happens is you have a lot more surface area now for that cell to take in nutrients, to expel nutrients, to have oxygen from the from the serum of the blood enter enter a cell. So for for cells to shuttle oxygen through the bloodstream, they need to have more surface area. To increase the surface area, you need to create create cellular separation. To create separation, you need to have the right charge. Tell me

Ben Greenfield

about the protocol we did today and what all you use for for exercise exercise with oxygen therapy. Yes, exercise

Gary Brecka

with oxygen therapy, and we do this with a lot of our professional athletes that we're trying to get to the next level. I'm working with a lot of athletes that are playing in the league right now that are dominating their game. Some of them are very public about their relationship with me; some are not. But we are measuring their performance using magnetism, oxygen, and light, which is NSF certified, it doesn't. It's not considered performance enhancement. It's considered reparative, regenerative, and we're seeing incredible results with tissue repair, regeneration, protein synthesis, increase in protein synthesis, and muscle repair and performance. But not, you know, Ewan is a 1011, minute time frame where you're

Ben Greenfield

went by super fast, hyper not drained afterwards. Like after a big workout, you're energized. Too

Gary Brecka

much oxygen over too long a period of time will actually drive red blood cell down countdown, and that's the opposite of what you want. But for a short period of time, it took you 10 and a half minutes to do it today,

Ben Greenfield

right? It was three minutes, 333 minutes, 30 seconds after after each breathing pure oxygen.

Gary Brecka

Yeah, breathing not pure oxygen, 35 high oxygen, and it's just

Ben Greenfield

like a. You have an aerodynamic bike. You have the mask next to it. I'll put pictures for folks at bengreenfieldlife.com/breka. I told you my my protocol is kind of sexy too. Like I got the Vasper, which is the blood flow restriction,

Gary Brecka

right?

Ben Greenfield

And the grounding and the earthing because you're grounded to the to the plates on the Vasper, and then the full body exercise. And I keep the Live o2 next to that because I got a switch. And so during my recoveries, like the long periods, you go hypoxia, and then during the efforts, you go hyperoxia and flood the tissue oxygen, and that's 21 minutes. I'm I felt as though your 12 minute protocol beat me up a little less than the maybe I'm I'm going too long with the Vasper protocol, but nonetheless, the takeaway message here for people is it's high intensity interval training with periods of time during that high intensity training where you have some kind of a mass to deliver higher amounts of oxygen to the body,

Gary Brecka

and and 10 and a half minutes is all you need. You breathe 900 liters of 95% o2.

Ben Greenfield

Now something I've always wondered: what if you were to use? Let's say you didn't have the money, or you don't have access to the oxygen delivery system mask that you wear. What if you just during the easy periods were to wear something like a training mask, you know, or like resist oxygen intake, or even breathe through a straw, do you think you could still get some effects by then during the hard efforts, just like opening your mouth and taking the training mask off and breathing? I absolutely do. I mean, if

Gary Brecka

you look at the you know cyclical breathing methods of Wim Hof, you look at exercise with oxygen therapy, a lot of these have the same foundational concept, which is one: create a demand, and then two: answer that demand. And and what I mean by that is, we know that we can't just eat a bunch of calcium and have strong bones, right? You have to load a bone,

Ben Greenfield

yeah, and

Gary Brecka

then have calcium there to help build it, yeah. Right? We know that you can't just eat a bunch of protein and build big muscles, right? You have to tear a muscle, then you have to have the protein available to repair it. Right. The same thing is true with oxygen. You just can't sit and hyperventilate and flood the body with oxygen. What you have to do is create an oxygen demand. So the idea behind Ewan is exercise is putting an oxygen demand on the body, and then when it's same as a breath hold, in a in a Wim Hof method, for example, exhale breath hold. Why is why are we exhaling and holding our breath? Well, you're resetting carbohydrate or carbon dioxide receptors. Yeah, actually driving the level of that gas up. Now, when you breathe in, the tissues just they take it up, so it might

Ben Greenfield

not be perfect, but you could you could basically the way you want to think about it is this: during an exercise session, try to deprive yourself of oxygen, then throw in a few high intensity intervals where you're just opening up the portals and flooding yourself with oxygen, and you're at least even if you don't have the fancy equipment, kind of like going outside barefoot gives you a taste of the PMF. Doing that will give you a taste of the EWO.

Gary Brecka

Can hold your breath and do push-ups to exhaustion.

Ben Greenfield

That's a great idea.

Gary Brecka

Breath work.

Ben Greenfield

How do you describe immune aging? And you know, I hear terms like inflammaging and immune senescence and immune cell exhaustion. Can you walk us through what all these things actually mean?

Dr. Anurag Singh

Yeah. So, I'm a trained immunologist. After my MD, I did further training in immunology. So, immune aging to me is everything you just mentioned. Immune aging is sort of the sequelae, and there are three key hallmarks to this sort of phenomena. One is inflammaging, which means as we're getting older, our cells are getting fatigued, damaged, and these sort of damaged zombie-like cells become triggers of inflammation in our in our cells and organs and body, and that kind of keeps increasing as we age. So from our 30 s, 40 s to our 50 s, 60 s, our bodies, as my professor would say, is swimming in a sea of or milieu of these soluble factors that we call immune cytokines, and these are basically damaging our organs. So that is inflammation in in sort of broad context. Then there is these terms like immunosenescence, which really means your immune system just does not have the ability to, you know, be what it was in our 20s and 30s, and that's primarily because we have this organ called thymus, you know, up right here, and around our 20s it starts involuting, means shrinking, and as it shrinks, and that's the organ that makes a lot of immune cells, and the most renowned immune cells it makes is something called T cells. Immunologists are not very creative people; they just thought about few cells and call them A, B, C, D all the way till T. And so these are T cells, which stands for basically think of them as the elite forces of the army of the immune system, and they are patrolling all the organs for when is the next big threat coming, whether it's autoimmunity or an infection or even cancer, and so these kind of disappear and become very fatigued, and that's the phenomena called immunosenescence. And then there's a third term called immune resilience or immune sort of fatigue. What happens is that these immune cells, T cells, B cells, all the you know sort alphabetical names that come with these immune cell, they have mitochondria that over time get fatigued, and they just don't have enough metabolic capacity to keep fighting cancer, keep fighting infection, and so that's sort of all encompassing into immune aging.

Ben Greenfield

Okay, so when we talk about you know longevity and anti aging, and I'm not one of those guys who you know endorses the idea of just trying to live no matter what to 200 years old. I'm more in the camp of live as healthy as possible, as close as possible to the day that you die, but when we talk about the immune system, how much of an impact does that actually have on longevity? Like declining immune health, you know, because you hear about declining mitochondrial health or you know declining brain health. How big of an impact does declining immune health have on longevity?

Dr. Anurag Singh

So, I mean, we've all talked about in probably it has been talked about in your podcasts before this whole idea of hallmarks of aging, right? So, biological hallmarks of aging are these very interconnected biological pathways that all decline together with aging, and I believe there are two or three key in these, there are 12 of them now. You know they range from our genes getting altered, or the environment impacting our genes, or poor nutrient absorption as in our cells. But the two main ones, I believe, are mitochondrial dysfunction and chronic inflammation, or inflammaging, or immune aging, and I think they're they're really linked together very closely, and when I say linked together very closely, I mean I personally believe that immune aging is sort of the central piece, and that's the trigger for a lot of these hallmarks of aging. So if you slow down immune aging, immune cells are in all organs, and if they go problematic, then you are impacting what I call the organ rate of aging or cellular aging. We are finding evidence that things like changing exercise regimens or diet or even mitochondrial interventions actually alter these two key hallmarks, and they're very closely linked: mitochondrial health and immune health.

Ben Greenfield

So why is it that I mean you say that immune aging and mitochondrial health are kind of very much related, but why is that? What's the link between the two?

Dr. Anurag Singh

Yeah. So you know, as I was starting to mention that immune system, the way I see it, it's almost like a, you know, like a policeman of the entire body, all the organs. The immune cells are everywhere. So, when something goes wrong, in a bigger picture, who comes in? The police comes in, right? And so, as we age, when the cells. In our organs are not optimally functioning. The immune cells kind of come in to survey if everything's going all right. If you know all the organelles are etc. and inside the cells, the neighboring cells, they're talking to each other, and so what they're almost like a surveillance program. This immune system, and what happens is as soon as the cellular health declines, okay. So as as soon as all the different hallmarks start declining, the immune system is the first to put its hand up and say, "Hey, there's something going wrong, and it starts to survey. And at a certain point, it cannot because it just gets overwhelmed, and so I believe the immune system is like the sentinel of our healthspan decline. And as soon as we hit our 30s, 40s, and the first wave of you know biological changes happens, the immune system is the first one that fires that shot and says problem, okay, and so it and the connection between mitochondrial health and immune cells and immune health is there are it's a field we call immune metabolism. So the policemen in this case the immune cells need energy to To be able to survey all the organs, the key metabolic organs that decline with aging, and so they run out of gas and they run out of fuel because mitochondria power them up, and so one of the fixes we think is by sort of reenergizing or rewiring the immune system by boosting the mitochondria, and that's the connection.

Ben Greenfield

Okay, so in the case of urolithin A, then does it have more an impact on the mitochondria, or is it working on some other element of the immune system?

Dr. Anurag Singh

Yeah, so Urolithin A, from the time you take it orally, will hit mitochondrial health in every cell that has mitochondria, and all our cells except the red blood cells have cellular mitochondria. Now, the more metabolic ones, like the neurons or the skeletal muscle cells, they get hit hard the most. So the things that happen the most frequently with aging is problems getting up from a chair, problems walking, and that's mostly because your muscle cells do not have the right energy source, which is mitochondria, able to power them up. Same with neurons. The first thing that will happen is decline in cognitive health, and this equally to things like Alzheimer's. I believe it's you know when when you take uritin A, not only are you hitting mitochondria in your skeletal muscle cells, theoretically in your neuron cells, and you can even target brain health via that. But what we are discovering is that the mitochondria in inside the immune cells, these T cells and B cells, they get recharged and they kind of propel the immune system to start surveillance at a at a at a much better way, and so that kind of links to aging and mitochondrial health.

Ben Greenfield

Okay, got it. Let's let's get into mechanism of action here. You use the word like hitting the mitochondria, recharging the cell, but in terms of a little bit more of a scientific explanation of what that means, like hitting, recharging, etc. What is urolizinate doing to the mitochondria? Yeah,

Dr. Anurag Singh

so you can power up your mitochondria three ways today, or at least three known ways to scientists and and doctors. One is a process we call mitochondrial biogenesis. So this the sort of pathway you if you're hitting exercise is well known way to induce mitochondrial biogenesis, which means just create new healthy mitochondria that create more near energy, more healthier energy, and you power your cells up. That's one way, and there are compounds like NAD modulators, things like resveratrol. These are all known mitochondrial biogenesis agents. The second pocket is you have your healthy pool of mitochondria. You know, I see you're exercising, so you're already inducing biogenesis. But how do you keep these healthy mitochondria up and running and become more efficient? And that these are things like creating CoQ10. Now, what your Latin Amitopure is doing is hitting what I started described process called mitophagy, which is basically damaged zombie mitochondria. So as we are aging, our immune cells are aging. Their mitochondria are getting more and more damaged because they just can't keep up with, for example, all the viruses and bacteria. They have to the onslaught that happens with aging, and or cancer sort of mutations that start happening, and so they need to be recycled, and that's what we are seeing when we take the immune cells, these T cells, out from people who are who are aging or 7080, years old. We see exhaustion in these immune cells, and what that means is basically they. Mitochondria are not able to induce properly the energy currency, which is ATP. When we give them mitopure, whether in you know in our randomized trial, which we can talk about, or in cell culture, we see more PGC one alpha or biomarkers linked to better mitochondrial health starting to show up in in these immune cells, and when we put, for example, these immune cells with bacteria, they kill them better. So that's the you know sort of biology that we are seeing happen, which is really mitophagy. We had started with muscle cells, and we we focused on endurance and performance and strength benefits. But what we are actually discovering now, as a sort of additional benefit, is that you lower inflammation, you recharge your immune system, and even in you know athletes, for example, athletes are well known to have a lot of overtraining induces inflammation. We are seeing that get blunted. So that's the connection.

Ben Greenfield

Okay, I've actually never heard it explained that way before. So you have mitophagy. That's like one of the three things that you said. That's the last one that your lithonate focuses on, like the mitochondrial cleanup. You said mitochondrial biogenesis, and I think you said that one's more triggered by things like exercise.

Dr. Anurag Singh

Yeah, exercise, fasting. Okay, known modulators. Yeah.

Ben Greenfield

Okay. And what was what was the third one? The

Dr. Anurag Singh

mitochondrial efficiency. So this process, you know, you always have in your cells this yin and yang of healthy mitochondria and damaged mitochondria, and this sort of balance in between, and that's always going on. You know, even when we're healthy, young, we always have this process continuing, but what happens with aging is mitophagy slows down, biogenesis slows down, and so you're basically shifting that balance towards all damaged mitochondria. And so what we see is mitophagy is the actual trigger to clean out that waste, almost like the Pac-Man of cleaning up shows up and cleans the waste, and now that is recycled and triaged and put back as recycling, you know, building blocks of near healthy mitochondria, which is biogenesis in many ways. Okay, so like in an ideal scenario, you're you're exercising, you're fasting, you're doing things for mitochondrial biogenesis. Yeah, you're getting some fuel in with things like NAD, creatine, healthy diet, etc. for the mitochondrial efficiency, and then for the mitophagy, you're introducing a component like urolithina. Yeah, and and that is actually I described it one after the other, but I think think of a little town, right? Or think of a little town where you have X amount of buildings you can have, unless you clean the damaged buildings or the damaged portion out, you can't really build new stuff, and that's what mitophagy or autophagy is. You have to clean out the damaged cell, damaged cellular machinery, and that again gives way to real estate, and now you can do the building block. So we have thought about it. We've combined urolithin. We've tested in different models of aging where we have combined exercise with urolitin A. We get a better augmented response. We've combined caloric restriction with urolitin A supplementation. We've got a better response. We've actually done now two or three randomized trials in athletes where people are training and they're finding in these different trials some of them are published some are not that your Latin A actually augments even the the performance of exercise or the impact of exercise.

Ben Greenfield

Yeah, that's actually what I wanted to ask you about because like three months ago you guys sent me the new RCT. I think it was called Mido Immune. That's what got me interested in this whole topic of mitochondrial and immune aging in the first place. Tell me about this RCT.

Dr. Anurag Singh

Yeah, so this you know this a long collaboration with the two of the pioneers in the field of studying immune aging. One is Professor Eric Wardin, who's the CEO of the Buck Institute of Aging and has been studying immune health and the impact of immune aging on health span for the last 35 years. And the other is actually a cancer researcher who, many years back, came to us and and basically in different models of cancer. What he saw was that actually the immune system was failing, and it was failing in part of what I was describing, surveilling you know the the cancer prone cells because of mitophighy issues. So mitophagy decline and cancer incidence in the in these models went up. So he came to us and he said, "You've published, and at that time we've just published that urethane was a mitophagy agent and enhancing muscle health. But he was very interested in using it as a way to sort of recharge the immune system in the fight against in these models. Of cancer, and so he published actually two three years back actually when we first spoke in a in a very prestigious journal, but it was an animal study in a in a model of colorectal cancer. When he supplemented with with urolitinae, he saw that he saw basically better immune system and more mitochondria in the immune cells that would then lead to sort of better cancer survival in these models, and so we said, well, we don't want to do cancer yet. Let's start and see what happens with this molecule in healthy middle-aged adults, because we had seen the effects on muscle in middle-aged adults. So we ran a trial where we selected from hundreds of people about 5060, years of age, they were a bit overweight. Some of them were exercising, some were sedentary, and we gave them, we randomized them into two groups. Now the way top tier clinical trials are done is you do you have a control group, a placebo group. So we took 25 participants, we gave them placebo, and 25 participants, we put them on a gram of urilitamina mitocure, and we did serial blood draws. So we, before they started the supplementation, we took their blood and we ran something called as as complete immune profiling. Now this not what your standard medical doctor will do, but this a technology that, with from a small amount of blood, I can profile all your immune cells in your body, and there are trillions of them, and I can see the immune age score of all these cells, basically. And so, what this professor we are collaborating, the CEO of the Bucking City of Aging, Professor Wardah, he profiled them, and what we saw was really shocking was that we almost saw the 50 year old persons with healthy immune cells that were fatiguing, that were inflamed. They almost reversed back to probably what a 3040 year old person's immune system will look like. Wait,

Ben Greenfield

and these when you see immune cells, these are the T cells.

Dr. Anurag Singh

Yeah. So you

Ben Greenfield

okay?

Dr. Anurag Singh

You you take the when you do a blood draw, you get total blood cells, and you can take the red blood cells out, and what you're left with is what we call white blood cells or leukocytes. Now these are you know the let's say the main cell immune cells in our body are the T cells. They're about 10 to 20% of your immune cells. Then there are the B cells, which make antibodies, and and these are another 20 30% And then there are cells called neutrophils, which are like you know the they're not the police, but they are kind of the first responders, and so they kind of they they give the first shout out to these immune cells. And there is something called dendritic cells, which are basically immune cells but with tentacles, and they are always surveilling whatever infection or cancer you know prone cells are are loitering around. So we actually profile all of them, and amazingly, the mitochondria in all of them went up, which means now the immune system has more energy to function. But what struck was two kind of cells that are needed to fight cancers and are needed to or decline very fast in aging process. These are the T cells. These are the what we call the cytotoxic T cells. They fight cancer. They fight flu. They fight any virus that you have growing up. You have lots of them, and as you age, you kind of lose all of them. And so we see them kind of coming back to the you know almost like repopulating in the body, and and then the inflammation was much subdued in these people, so these are the three key findings from this trial.

Ben Greenfield

You know, a lot of people. This just makes me think about this. They, whether for cancer or, I mean, I've done this just as almost like a longevity play. They'll go overseas into killer cell infusions. Have you heard of this?

Dr. Anurag Singh

Of course, yeah. So you know, I didn't want to get too nerdy, but we look at something called natural killer cells, which is abbreviated to killer cells. So the two main cells, if your body just loses them, your chance of getting cancer is like thousandfold higher, and that's these cytotoxic T cells and the killer cells. The killer cells are about a percent to 2% in your body, and we see them, their mitochondria also getting recharged, and we see the increase in these NK cells or the natural killer cells, the cytotoxic ones. So, as an immunologist, I think these are the two main cells you have. And so, of course, what you are seeing today is, if you go all the way to cancer treatment, is two kind of therapies, as you were saying, NK cell or killer cell infusions, or something called CAR T cell infusion, which is basically where you take a T cell and you artificially put the cancer sort of signal on it, and then you inject it into the into the cancer patient, and because the. Now they have seen it in a dish. They'll multiply and they'll they’ll clobber the cancer. So these are the two main cells we're seeing the effects.

Ben Greenfield

I want to definitely get into your history and how you got into longevity in the first place, and and all the little things that you're doing to be so high on the leaderboard on the Rejuvenation Olympics. But I don't know if you're familiar with this researcher. Probably the foremost researcher who kind of has raised an eyebrow at endurance sports and the potential for things like atherosclerosis or arterial stiffness or excessive aging from excessive endurance exercise. Dr. James O'Keefe, you know, he certainly brought to light the idea that too much endurance exercise could cause a lot of inflammation, or accelerate aging, or cause arterial stiffness, or you know, or plaque buildup, or things of the like. Have you ever thought about that?

Dave Pascoe

Oh yeah, I don't really think that endurance running is healthy for me. It was something I do for charity, so I'm willing to take the hit for the cause. But it's not something I do for my longevity.

Ben Greenfield

But yet, you seem to be doing a pretty good job based on your your TruAge results. Despite that,

Dave Pascoe

you know, originally back like in 2012, I think I learned this from you actually, listening to one of your podcasts or probably reading one of your blogs back then, I learned about telomeres and how they shorten with age every time a cell divides, and I learned about the telomere test that you could get. So I got the test thinking that you know, hey, I'm going to be really in great shape. It's going to come back and tell me I've got the telomeres of a 20 year old, right? I was just turning 50. I was just starting my first marathon, so I was deep into the training of that. I was doing P90X. I had a really stressful job. I was taking care of both of my elderly parents who were battling cancer at the same time, and I took this test, and I said I had the telomeres of a 68 year old at age 50, and I was pretty shocked because that was not the results I was expecting. Yeah, ended up taking a. They had you could make a consultation call with them, and so I took the call because I wanted to find out what they're what possibly they could tell me. And one of the first things they asked me, which puzzled me, is they wanted to know about my lifestyle. You know, and at that point in my life, I knew lifestyle mattered somewhat. Like you know, what you eat, how well you slept. You know, exercise was good, but I guess I didn't understand the depths of which my lifestyle was causing me problems. Because as I started to explain to them about the stressful job, taking care of my parents, doing P90X, doing the marathon training, they're like, whoa, whoa, whoa! Stop right there. We've seen this before. We've seen this in endurance athletes that have very short telomeres. We've seen it in people who are caretakers. Same way, we've seen it with people who have incredibly stressful jobs. So basically, they explained to me that the stress that I was putting myself under, both you know emotionally and physically, was eating me alive. So they suggested that I start, you know, maybe looking into doing things like yoga, meditation, things that I had been doing earlier in my life, and I just completely forgotten about. I mean, you get busy the day-to-day life, and you certain things fall on the floor, and those were two of the things that I stopped doing. So, yeah, for my sanity and for my health, I had to start including more rest days. Had to drop P90X while I was doing the marathon training, get back into yoga, more meditation, a lot more sauna, things that were better for my health.

Ben Greenfield

And where did the Rejuvenation Olympics enter into the scene for you?

Dave Pascoe

That was kind of by surprise because I didn't know anything about it when I was doing my TruDiagnostic testing. I learned about TruDiagnostic again. I suspect it might have been from you back in the day. It was some podcast, but it was probably you, so I was using them as just another you know another marker for how I was performing, like just to validate that my supplementation was not causing me harm and was pointing things in the proper direction. So I just happened to have my third qualifying test when I became aware of the competition, and I remember looking at my results and thinking, "Wait a minute, this this can't be right. Am I actually beating this this billionaire guy? I'm thinking I must be misinterpreting the results.

Ben Greenfield

Do you mean Brian Johnson?

Dave Pascoe

Yeah, that guy. Yeah,

Ben Greenfield

okay.

Dave Pascoe

Yeah, and so I submitted my results, thinking that they were just going to come back and tell me, "No, no, you're misinterpreting that. You're not. You're not beating Brian. Or it would have been that I was beating Brian, and then the question was going to be, "Will they actually, you know, publish?" Results if I'm beating him, and to their credit, they did

Ben Greenfield

right. And and you would question that just because I think he's involved with promotion of the Rejuvenation Olympics, and I you know I know Brian, I've interviewed him. I think he's actually you know an ethical guy. I don't think he would like tweak the results to ensure that you know so he could sell more olive oil. He'd appear towards the top of the charts. It doesn't appear that he's he's doing that, but you know, similar to when I saw Julie Gibson's Julie Gibson Clark's results, you know, I saw yours. I've met you a couple times. You know, saw you down in Austin, and I thought, well, gosh, like you know, he's he's definitely not getting young blood transfers, but and you know, still doing endurance training and you know, climbing Mount Kilimanjaro and you know, doing the things that you're doing. So I thought it was very interesting that your pace of aging is so low.

Dave Pascoe

Yeah, that was very surprising to me as well. I think even at my worst, my pace of aging. I think my highest test was maybe 0.8. I think it was

Ben Greenfield

right. And what's your what's your best result for your age pacing?

Dave Pascoe

0.66.

Ben Greenfield

So for so for every year, like if you take 365 days of every year, you would only be aging for 0.66 of those days, which comes out to what 250. Doing rough math in my head, 250, 260 something days.

Dave Pascoe

We get seven months. We age seven months for every calendar year, so we get the other months for free.

Ben Greenfield

Yeah, how much of this do you think is contributed, or how much of this is attributed to genetics? Like, what do your parents look like?

Dave Pascoe

If you saw my family, and I don't want to throw my family under the bus, yeah, I wouldn't say that any of us look particularly young. In fact, my family tends to be overweight on average. Although you know, both of my parents have since passed, and they both lived to the ripe old age of 89, despite not exercising, smoking, drinking, not eating well. So I don't deny that there's some good genetics there.

Ben Greenfield

You're not really into like the calorie restriction thing.

Dave Pascoe

No, not at all, not at all. In fact, my friends make fun of me when we go out to restaurants because I will order two meals. I eat like a pig. I don't. I don't count calories. But usually, when I'm eating at home, or even when I'm eating out, the very first meal that I have is an enormous salad, so I'm stuffing myself on you know vegetables to start with. Then I usually follow that up with a meat and maybe some carbs, but the meat would be you know condiment size portions. So I like to say I have a favorite restaurant. It's Ford's Garage locally. The first thing I'll get is a berries and gorgonzola salad with shrimp, and it's huge. It's a meal in itself. It's larger than my head, maybe two of my head put together, and I'll eat that first. And then people are like, "Wow, you really killed that! And I'm like, "Yeah, that's only my first meal. Then I order the mushroom Swiss burger with avocado and an egg, sunny side up, and then yeah, I kill that. Usually get like a side of either their mac and cheese, or if I'm really behaving, it's just a big side of broccoli.

Ben Greenfield

Well, I've seen a lot of restaurant menus. That right there that you just described is probably pushing around 3000 calories for a meal.

Dave Pascoe

I wouldn't be surprised. Yeah,

Ben Greenfield

yeah. Okay, so why is it that you aren't on the same kind of like calorie restriction bandwagon as a lot of these folks? You know, even Brian Johnson. When I interviewed him, I think he said, you know, every calorie has to fight for its life. What is it about your protocol that inspires you to just kind of eat ad libitum?

Dave Pascoe

Honestly, I don't know. I really don't know. I think it's because I'm just so physically active during the day that I'm burning a lot of those calories, and so I know my I know my metabolism is fast because of that.

Ben Greenfield

All right, another thing I found out about you, Dave, is you've got pretty decent testosterone levels, but to my understanding, at least as far as I know, you're not using testosterone replacement therapy.

Dave Pascoe

That's true. Tell me about that. So when I started looking at my markers, I noticed like my DHEA and my pregnenolone were a little low compared to what I thought they should have been for a healthy collegiate athlete. So I began supplementing with those, and I think for for folks that know things about hormones, they know that those are upstream precursors of testosterone and estrogen, and if you supplement the upstream precursors, you're going to get boosts in those downstream hormones. And I saw a pretty good size, you know, increase in my testosterone from doing that. I also saw that from just getting out and running, I got a really nice kick in my testosterone. So I get I get frustrated when friends of mine tell me that you know they just go right to their doctor and get testosterone replacement, and their doctor didn't even check any of those things, and they didn't try any of those things for.

Ben Greenfield

Yeah, addressing the lifestyle and other supplementation factors. What what are your levels at, by the way? Do you know what your total or your free levels are at approximately?

Dave Pascoe

I so I don't know this month, but I check usually every month, and my range from like in 2023 went from about 809 to like 1295. I think it was.

Ben Greenfield

Oh, holy cow! For a TRT-free 61-year-old, that's that's really good. Do you want free access to comprehensive show notes, my weekly roundup newsletter, cutting-edge research and articles, top recommendations from me for everything that you need to hack your life and a whole lot more? Check out bengreenfieldlife.com. It's all there, bengreenfieldlife.com. See you over there. Most of you who listen don't subscribe, like, or rate this show. If you're one of those people who do, then huge thank you. But here's why it's important to subscribe, like, and/or rate this show. If you do that, that means we get more eyeballs, we get higher rankings, and the bigger the Ben Greenfield Life Show gets, the bigger and better the guests get, and the better the content I'm able to deliver to you. So hit subscribe, leave a ranking, leave a review if you got a little extra time. It means way more than you might think. Thank you so much.