535: A longevity drug exists—would you take it? | Nir Barzilai, M.D., leading longevity researcher

Welcome to the MyBodyGreen podcast. I'm Jason Wakab, founder and co CEO of MyBodyGreen and your host.

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If we had a drug to delay aging, would you take it? According to Dr. Nir Barzilai, that longevity drug does exist and it's more accessible than you think. Nir is a chaired professor of medicine and genetics and the founding Director of the Institute for Aging Research at Al Albert Einstein College of Medicine. He is a renowned longevity researcher studying families of centenarians that have provided genetic insights on the protection against aging. He is the author of over 270 peer reviewed papers and is currently leading the TAME study which shows that the drug Metformin, yes, the drug used in patients with type 2 diabetes, has the ability to delay the hallmarks of aging. Look, we believe lifestyle interventions are crucial and on a personal level, I tend to think of pharmaceutical interventions as a last resort. But look, lifestyle may only get us to 80% there and Nir's work shows us that pharmaceuticals might be able to get us to that 100% that I think is Fascinating. And many of us are looking for. Tune in to hear his updated research and I think you'll find it fascinating.

Anti aging wasn't something that we scientists in the field of use. And by the way, just for you to understand, we call ourselves geroscientists. Okay. And that's why we're talking about gerotherapeutics. And this is the problem. I think you guys all know that we have a lot, a lot of products out there. People are marketing a lot of stuff, and a lot of it is about hope and very little of it is about promise. And even less is realizing a promise. Okay? So there's a lot of noise. And actually in our science, we're trying to really understand the biology, understand how we can target aging, how we can slow aging in a scientific way. And we need to distinct between the noise, what we call noise, and between the real things. And that's why we're looking for geroprotection or gerotherapeutics. And anti aging, we prepared. It's our enemy. We also don't like to call anti aging. Right. I mean, we're not against aging.

You want to age, but you want to age well. And getting back. I love your point. Hope, as I've joked before on this podcast, even though I am a man of faith, I, I, that's a big part of who I am. I also believe hope is not a strategy. And so you mentioned the noise and the science. In your view, what is the noise? What doesn't really have science behind it and what does as we think about this evolving field?

So I would make some comments here. I see that you haven't interviewed Brian Johnson.

I have not.

Should I or not yet?

Will, I've interviewed Peter Attia.

Yeah, but Brian Johnson, I want to bring Brian Johnson because it answers your question. Okay. Brian Johnson is a one guy that's doing an experiment with himself. You know, for scientists, this is a. No, no. Okay. Because it's also very personal. You know, every one of the audience know that they got some suggestion from friends that it worked for them, but it's not working for you. So somebody doing an experiment doesn't mean that it works. By the way, I'm most worried about Brian Johnson, that he'll die and then he'll take our field backwards. Right. But he's using 115 supplements or not by now, 120 supplements. And we assume that if we take. I understand why he takes each one of them, but he assumes that they'll add to each other or Even will synergize each other, which means make it even, even better. When in fact there's a lot of supplements that will antagonize each other. So. And we don't know, we don't know all of it. But, but believe me, when you take 115 supplements, assuming that they have what they claim, which is a different issue. Okay, but, but if they do, there's a lot of antagonism.

Well, let's talk about that for a moment. One, I'm glad you pointed that out because that's something I've struggled with with him. I appreciate the transparent transparency. I appreciate what he's investing in his own n of 1. But I agree for many the takeaway is, well, I can do this too, but we'll touch on genetics. And that's, that's not where the field is going. We're all personalized individuals. And just because an N of 1 works over there doesn't mean it's going to work for you. But something I want to call out. You mentioned supplements or certain nutrients potentially being antagonistic towards each other. What's an example of that?

Let me give you an, an example you might edit later that. But an example that I'm thriving. A good example that will answer a lot of that. But okay, let me finish my thought about supplements and then I'll go straight and answer you. And by the way, what I like about supplements is they're good for the economy. Okay. There's really a lot of economy around and I wasn't worried about it because until the last couple of years, we know that a lot of the supplements didn't contain a lot of the supplements or some of the supplements are unstable. So if you took them off the shelf a month later, there was nothing active there. But this is changing rapidly. So now I'm worried that a lot of the supplements are there, but I'm talking about supplements because of another reason. There are about 12 FDA approved medications, FDA approved medications that are also gerotherapeutics, which means basically when you give it to animal, they live healthier and they live longer. Some of them have been given to humans who also live healthier and have less mortality. And I think that our approach, when we come to longevity medicine, when we come to longevity physician, I think we should use those drugs before supplements, right? We are thinking, you know, supplements are mainly nutraceutical, you know, they're healthy. But if you have an FDA approved drug, you know that the safety has been assessed, that the efficacy has been assessed, that there's year of use that you know a lot about those drugs because believe me, supplements have their own side effects. Just like drugs. Drugs can, supplements can become drugs. There is a movement to move more supplements to drugs. It's the same problem. Exactly. They all have tradeoffs, they all have side effects. There might be, there might be drugs that save hundred people, but kill three. We need to understand that.

Right, I agree. I think I have a couple of thoughts. I'm glad you brought this up. One, I think the world is merging where pharmaceuticals and supplements can be used together with lifestyle modification to make real change. I also believe that, you know, across both industries, you've got some good actors and you've got bad actors. Whether that's intended or the consequence of maybe cutting quarters or potentially putting profits behind efficacy, I think it happens on both sides to, to some degree. But I do think this idea, and I'll, I'll segue to metformin. And I think sometimes people have a view in our world which tends to be more holistic, that, you know, pharmaceutical bad, supplements good, they almost get a pass. And to your point, when there's a great claim, there's often a great side effect and you need to be mindful of that. You should always work with a practitioner. And so I'll segue to metformin. I think it's a good example of the nuance here. Metformin is a drug, it is a pharmaceutical, it is FDA approved, but it's derived from French lilac. From nature.

Exactly.

And so let's talk about. I'm going to back up before we go straight into Metformin. So you study longevity and more specifically health span because it's not just about the years, it's the quality. And something I heard you say, and this is real and I think this is really fascinating and kind of sets the stage for a conversation. The CDC did a study of healthcare costs for those who die at 70 versus those who die at 100. One would think, you know, oh wow, healthcare costs if you die at 100 are going to be much more significant than age 70 because you're living longer. No, if you live to 100, it's almost a third of the cost the living to 70. So let's pause there. Let's talk about that.

So I have 750 centenarians and their families in my study. Right. And the first thing we were interested to know is, okay, do they get diseases? When we all get diseases starting like at age 60 and then all they're doing is they're living longer with diseases or is there health span or lifespan? Does it go together? And we found the latter. Okay? I started collecting centurions in 1998. So my centurions were born in the late 1800. When they were born, life expectancy was 40, okay? If you got to 50, it became 60. Okay? But basically half of their friends have died 50 years ago, okay? They got diseases 20, 30 years. When we compare them to people who are living now, okay? So it's their children's age cohort. So they lived healthy, healthy, healthy, healthy. And not only long. And it's not even the point. The point is that they got sick for very short time at the end of their life, if at all. We have 30% of our centenarians didn't have any disease and didn't take any medicine, okay? And many of them just didn't wake up one morning. So there is what we called a compression of morbidity. And this is really being healthy and dying fast, which is kind of what we want. Right? That's what we're driving. We want to live healthier, we want to live longer, and we don't want to have disease at the end. So this is really the medical cost that the CDC has established. But I think it's totally underestimating. And there's a professor of economy that had to tell us that because for us, for us physicians, the criteria was the medical cost in the last two years of life. But he comes and says, just a minute. So you're telling me they're not in the hospital. Okay. But what are they doing? They're traveling, they're shopping, they're investing, they're buying houses for their kids. So there is an economical value that you underestimated. And when he estimates this economy value, it's basically something like 36 trillions dollars a year. Okay. Or 360 trillion dollars in the next decade that we could save by finding how we can be healthier. Because, you know, 40% of the economy is pretty much healthcare, okay? So being healthy. Being healthy is not only what we want to do, it's also the solution for everything. He said, you know, 10% of that will solve global warming. Right. If we had $3.6 trillion that we try to do things, we'll get ahead much faster. So this is how we see that this is not only about health and longevity and you, but it's about us and our economy.

Yes. So talk a little bit more about the superasure study and how it differs. We've had Dan Buettner, he's a good friend. Mr. Blue Zones on the show numerous times talk about how it differs from blue Zones.

Look, Blue Zones are terrific, but I have to tell you, we are doing something very different, okay? Because Blue Zone is about the environment. Okay? We're looking for genetics. Why are we looking for genetics? Because 2/3 of the drug that have approved by the FDA last year were based on genetic findings. And so we want to understand what is this story in centenarians that slows their aging. And I'll tell you, it's not the environment because 60% of the men and 30% of the women were heavy smokers. More than 50% are overweight or obese. Exercise. Less than 50% of them do even like housework or walking. So they didn't get to be age 100 because they did something with the environment, something else slowed their aging. And that's what we are. We were trying to find. And that's what we. Not only did we find things, but two drugs have been developed in part based on our findings.

So I'm assuming you found very strong protective genes for those who basically did not partake in any lifestyle.

You know, and unfortunately it's not unfortunate, but it's not one gene. You know, there's a gene that either you have or not and you become a centenarian. You can get there in several ways. That's why we are expanding this study now. And, and by the way, if any of the listener know any centenarians, you go to the American Federation for Aging Research web to the Super Ager family study and we will send a kit and register your centenarian and they'll spit into a lab and we'll get 10,000 tests that will determine more longevity genes so we can turn them into drugs. Okay, this was a site call, but that's where they are. And we found substantial genes that had substantial effects and we turned them into medicine and there are few others on the pipeline.

So what are some of those genes? And we will definitely link to this in the show notes, but are there a handful of genes that immediately come to mind? So for those maybe who've got their 23andMe or 3 by 4 genetics or whatever gene test they've done, they're going to go home and just take a look and scan. Do I have any of these? Understood.

It's not one, but 23andMe has it, by the way. And, and I, I didn't re. I mean, I knew they had some. I didn't know that they had all of my findings, but I learned that because when I did 23andMe, I discovered that I have one of the longevity genes. I didn't know that and I don't have longevity in the family.

Which one do you have?

Well, one. One that interacts with growth hormone, which is really the main example. I want to talk. This growth hormone example is going to take us through nutraceuticals and metformin and through the antagonism and through everything. So, so yes, 60% of the centenarians have something that prevents the action of growth hormones. Now, there's only one hormone that's called growth hormone, but there are many growth hormones.

Okay, IGF1.

Yeah, IGF1 is an example. It's a main way to look at the action of growth hormone. So 60% of our centenarians have something that impairs the action of growth hormone. So this is the idea. The idea is, or the explanation is that when we are young, growth hormone is good for us, okay? It leads us to reproduction. It's important for our organs, for our survival. When you have growth hormone until the age of 40, when you have growth hormone, the higher it is, the higher this IGF1, this growth hormone that we're measuring, the higher it is, the more you're protected from variety of diseases and even mortality. But then you pass the age of 40, you pass the age of 50, and your body is aging, which basically means it's breaking down. Okay? So it starts breaking down. So what do you want? Do you want to spend the energy in growth or do you want to spend in energy and. Just a minute, let's concentrate on the breakdown. And this is basically the explanation and we actually proved it scientifically by using big set of data from the UK Biobank. We showed how it switches. It's good when you're young, it's not good when you're old. This is an hypothesis of aging that's called the antagonistic pleiotrophy hypothesis of aging. Not everything that good for you when you're young is good for you when you're old. You need cholesterol when you're young for your gonuts, for your testes, for your ovaries, for your brain. But if you have high cholesterol metabolism when you're old, you get into trouble, right? So this is a concept, this is one of the major hypothesis for aging. So that's how we can explain why growth, why low growth hormone is good. So our centenarians have basically the major genes that we find Are all those that related to growth. Okay. This is important also when it comes to metformin, to the Metformin study. And you mentioned that metformin is an extract of a French lilac. So it's kind of nutraceutical, but it's modulated. So uh, so it, it's a drug. And by the way, the French lilac has been used and metformin has been used in the 1920s to the, in the 1950s to treat arthritis and to prevent flu and to do many other things like that. When it was discovered that in diabetic patients it lowered glucose. So, you know, it's an anti diabetic drug, but not really. It started as an anti aging drug, you know, from the beginning. And, and it's, it's because it's anti diabetic drug because diabetes is so common, because there's so many studies on diabetes that we started noticing, hey, people with metformin, they don't get diabetes. People with metformin, they have less cardiovascular disease, they have less cancer, they have less Alzheimer, they have less mortality. Okay, so we know all that already. Why? Because metformin is a general therapeutic. It targets the hallmarks of aging. That's why it's a really leading drug in the fight for aging.

So you mentioned hallmarks of aging and let's spend a moment here because at the highest level we know aging, age is a risk factor for all disease. The older you get, the more likely you're going to get cancer. Heart disease, diabetes, cognitive decline correction.

Aging is the major reason risk factor for a disease. It's more for cholesterol to heart, it's more for obesity to diabetes. Okay, it's the major risk factor for disease.

But what are the root causes? What is it about adding years that makes us more vulnerable? What's, what's happening and how can we take preventative measures so that whatever's breaking down isn't breaking down. So we're in terms of lifestyle, diet, or what do we know, genes, pharmaceuticals, the whole kit and caboodle.

Yeah, boy, you ask all medicine in this one long sentence. So we define the biology of aging in a term that we call hallmark. What is hallmark? To be a hallmark for aging, you have to show that something goes wrong. And in fact, you can take young animal and make it go wrong and see that they are becoming old or dying. But more important that if you correct that, it extends healthspan and lifespan of your animal, if that's where you are, or if there's an FDA approved drug in humans, okay? That's what it takes to do to be hallmark. And there are 12 hallmarks. And I'm not going to talk about all of them because what's important to note is you don't have to target all those hallmarks to get an effect. One hallmark is affecting the other. In fact, until we realize that, it kind of confused us because we started talking, we knew we have a drug that, that extends healthspan and lifespan. And we used to say, well, it works that way. And somebody else said, no, it works the other way. And everybody was right. Because if you take an old cell or an old organ or an old body and you make them young, then you're going to fix lots of things. Okay, so what is the mechanism by what each drug is doing? Never mind now, but at the end it's the hallmarks that we're trying to change. So let me take this example of metformin and exemplify how it works. So we know, commonly known, your physician know, that metformin is anti diabetic drug. So it improves metabolism and the decline in metabolism is one of the hallmarks of age. Okay, but I said that, you know, if you're really gerotherapeutic, it's not only about metabolism. You fix other things. So I'll give you an example. During COVID nine papers around the world showed that people on metformin had half the hospitalization and half the death from COVID Okay, now those are association studies. So you don't know, I don't know. Maybe those on metformin are also are all taking some something else or they were thinner or their glucose was better, which by the way, wasn't the case. So a study in the United States that was published a little bit more than a year ago took population that got Covid and treated them within three days, mainly within one day of a diagnosis of COVID And in the New England Journal of Medicine, and I'm just saying it because that's our bible, that's the most important journal, it's not a minor journal, they published a paper that they showed that those people got less than 40% hospitalization and 40% of deaths from COVID Not only that, it decreased long Covid, that's in a Lancet, in the European journal, it decreased long Covid by almost 65%. So why am I giving this example? Because it immediately shows you that metformin, it's not only metabolism, it's also about your immunity. And there are other gero therapeutics that have showed to actually be good with COVID So if somebody now gets Covid, most people who get Covid don't feel so bad. But if you feel bad, take metformin.

So in your view, should everyone be talking to their doctor about taking metformin if they're a certain age or have certain markers, who are the best candidates for metformin with the intended use of increasing health span?

So one of, one of the problems and my interest in metformin is not it has shown to do everything. My interest is Metformin because I'm leading this study to show the FDA that this drug is going to prevent a cluster of age related disease in people without diabetes. Okay. In elderly people without diabetes. That's why, that's why I'm interested. It's a political interest. Okay. I need to show the FDA that aging could be targeted because if there is no such indication, we are holding ourselves with lots of promises and lots of drugs.

Okay, so on that note, how many, you know, Metformin is a drug that many people are familiar with, but maybe not in the context of longevity. It's diabetes treatment. So how many of the, the population that takes metformin? Is it 2%, 1%, 10% that takes it for longevity?

Well, yeah, I. Look, diabetes is like 5 to 8% of the population. And until now, you know, now we have new tools. We have the Ozempic, right? So, but, but metformin was used by people for 80 years in billions and billions of years of use. Because metformin is not that. You're taking it a week and that's it. You're taking it for life if you're diabetic. So there's so much information, we know everything we need to do to know about Metformin. Metformin is not going to surprise us. But there are things that we have to know in Metformin and one of them is that all those studies have been done in people over the age of 50. And remember I said not everything that's good for you when you're young is good for you when you're old. Not everything that's good for you when you're old is good for you when you're young. For example, metformin decrease IGF1, decrease growth hormone. So I said that's great when you're old, but when you're young it's not good. Okay? So people, when people, when Peter Attia is saying, you know, I started Metformin and I didn't like it and stuff like that, or well, why did you start Metformin? It's not good for you when you're young. Metformin, for example, when, even when you give to old people. And that's. I think that's, that's if, if anybody looks at the literature, they'll throw it on me. There's a study of Charlotte Peterson in Alabama that in, in. Actually, she's in Kentucky, I think, and she took elderly people, 75 years old and exercise them. Half of them were on Metformin and half of them were not. And she had a grand because her hypothesis was that metformin will make the exercise better. She was not ready to find out that the people who were on Metformin, the elderly people who were on Metformin, everybody who exercise their muscle grows, but those on Metformin, it grew less, significantly less. So they ended up with less muscle. What people don't realize, even those who read papers, and I read paper because I'm a scientist, I'm reading papers, very different. But I went to the supplement, and in supplement number two, they showed that they did four tests for force. Getting out of a chair and, you know, and lifting it was the same. Okay? They didn't have change in their function. They had exactly the same function. In other words, maybe it's a small muscle, but every gram of muscle must have been stronger because they were doing just as well with and without metformin.

Because you want to maintain your strength as you age, right?

So we took those muscles and we basically demonstrated that the genes that are needed for muscle are actually not good for aging. They call mtor. They're not good for aging. We try to block them, but that's what builds muscle. So those genes were increased, but genes that were protected, protective against aging on the other hallmarks of aging were actually better. So you had smaller muscle but better quality. Okay, so, so that's. But you have to realize muscle is just one organ, okay? We're talking about the brain, we're talking about the skin, we're talking about our immunity. So every drug, when you go into it, has its trades off. But most important, with metformin, you don't take it when you're young.

Well, on that note, too, I'm getting back. So I don't really love the term, but I'll use it anyway to get, to get to my point. Biohack. So how many, if is it 1% of people who are taking Metformin? Biohackers? I would say the lion's share. The overwhelming majority of people taking metformin Today are taking it because of diabetes, not, you know, your Peter tias of the world. Who doesn't? I believe, I don't believe he takes it anymore. But those biohackers, is that, Is that safe to assume? That's a very small population that are taking the drug in the context of. I'm good, I don't have diabetes, all my markers are great, but I want to live to 150 or whatever age it is.

So I, I don't know. I don't know. There's no data that I can quote. Okay. I, I saw a couple of years ago that metformin sales have increased, although diabetes has an increase. And there is Ozempic. Okay. And I'm assuming, and just by knowing what's going around, I'm assuming that many people are taking metformin to target aging. Now, when you're asking me who should take it, there's, there's no indication, you know, metformin was repurposed. And when I say repurposed without FDA approval, people have used it for obesity because on metformin you lose some weight. There's better ways to lose weight. It was repurposed for PCOs for young women with polycystic ovary and hirsutism. It was repurposed. It was repurposed for pre diabetes. Okay. And now it's being repurposed to aging. So people are doing experiment I wouldn't do before your age of 50 unless you're biologically, you know, have accelerated aging or that you have diabetes or pre diabetes. Right. Those will be good excuses to use it even before. But I wouldn't use it before the age of 50, and I wouldn't use it on somebody who's going to be a centenarian. Right. That is going to be healthy anyhow for, for 30. For 30 years. So what is the indication? I'm not sure that I can tell you the experiment that we're doing for the fda. You have to have something. You had to have a heart attack. Maybe you're a cancer survivor, maybe you walk slowly. We have to have something that shows that you're actually on the breakdown part of aging.

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So I want to bring it back to your superager study. What were Some of the other key learnings, in addition to genetics, can play a powerful role for many people. What else did we learn? What are some takeaways for our audience who want to incorporate some of these practices or modifications in their everyday life

so there's nothing more important, Right. First of all, it's just to realize the fact that they didn't interact with the environment doesn't mean that we shouldn't. I could tell you that one of my longest living person was Helen Kahn. I can. Helen Riker. Say her name because she allowed me. She's dead since then, but I met her at the New York apartment when she was 100 years old. And she opened the door and she was smoking. And I said, helen, nobody told you to stop smoking. And she said, you know, all the four doctors that told me to stop smoking, they died. Okay? And she lived to be 110. But my argument with her was always, you know, I don't know when you'll die, but maybe if you don't smoke, you even live longer, right? So the lesson is not that you can smoke because centenarians smoke, or you can be obese because centenarians eat, okay? It's the opposite. So the lessons from our centenarians are really not for the public. For the public. It's the opposite. That you can do a lot by optimizing your exercise, your nutrition, your sleep, and your social connectivity. Right? That's what we all say. We're talking about maximizing and we are talking also about what mechanisms are really important for aging. So I'll give you an example. When I started my research, and I started my research in animals, the model that always worked is the caloric restricted animals. You took rats or mice brothers, and one group, you gave them to eat whatever they want, and the other got 30, 40% less. Okay? So they were caloric restricted. And what you noted is that those who are caloric restricted were much, much healthier and leave to much longer, you know, 30, 40% longer. Really say, you know, a year longer. You know, mice leave two years, they live three years, okay? Really substantially longer. And this has become the Holy Grail. Because we never can do. We can give drugs, but we can never do better than the caloric, the calorie restriction. So people took it to say, you know what? You should have less food for breakfast, less for lunch, less for dinner. But this is not what the experiment was. Remember, we had those animals, we came in the morning, we gave them the food for the day. The caloric restricted animals were really hungry. And they ate all the food and finished the food within 20 minutes. And now they were fasting for 23 hours more. So it was not only caloric restriction, it's fasting. When we gave food to those animals during the day, a little bit during the day, every hour or two, they were thin, but they didn't live much longer. So in fact, the fasting is very important from an aging perspective. And that's why a lot of us, me included, we're doing intermittent fasting or some form of that. We're fasting for many hours during the day in order to upregulate what's important for aging. Okay, not, not, not necessarily for metabolism or weight loss or anything like that, but for aging. That's why we're doing intermittent fasting.

And this one, I'll just comment, you know, I, I followed Peter T on this one and I think it's interesting because I think it speaks to an earlier point of, of the pre 50, post 50 and this goes to diet more specifically protein. Where in Peter's view, and I think this is interesting, is in some ways you don't need as much protein once you hit 50. But then post 50 you potentially need more protein to maintain the muscle or at least the strength as you age. I think that is interesting in this idea. What's good when you're young may not necessarily be be good when you're, when you're older. And I think it also speaks with fasting. I think the challenge people have is, you know, you mentioned Brian Johnson. They can go a little bit overboard. Here we Talk in a 13 hour fast where it's essentially, I'm not eating late at night, I may be waiting a little in the morning or a 14 hour versus I'm fasting for three days and I'm wearing away because we all know that that's also. I just want to call that out to give people some context. You're not suggesting you're doing these crazy fasts?

Well, I, I don't. We, you know, I don't know what to. So let me tell you, women, we know a lot about intermittent fasting from a weight loss perspective. It works much better in men than in women. Women lose weight, but men lose more weight. So if that's why you're doing intermittent fasting, just be prepared. That's not going to work so well. The human studies are not a lifespan study. Right. We don't know what it does and when it does. And you're absolutely right. Every stage of aging and it's an individual is very different. Basically, elderly walk from obesity to leanness. And some of the leanness is not good because they're frail. Right. So what do you do when. So I'm really talking about people who passed 50. You know, 50 to 70 is kind of where the interventions are really good. Sometimes it's too late when you're older. So as you mentioned, there are many way to practice intermittent fasting. So, you know, I'm doing intermittent fasting that is based on the 16 fasting, 8. Eating where I'm actually most of the day is more like 17 hours. It's actually when I get to 16 hours, it doesn't matter. I can go for few hours more. But I can tell you that when I measure the things that I am expecting this fasting to do, they don't happen to me. Okay, so we still don't know what happens when. I had a study planned like that just before COVID and I couldn't do this study and I don't have the funding to do this study. But I think many people are trying to find how much time is really necessary. There are people who do studies with 12, 12, let's have two meals a day, right? And let's see what happens in between. We really don't know that in humans. What I told you in animals are, is true in animals. If you were a mice, I know what to tell you to do. But in humans we don't know. But for me, there are lots of things that have changed very dramatically, including my, you know, some fogginess or slowness that I would have, like in midday, they all went away. My exercise capacity have increased significantly. My lean body mass for some reason increase. It's at the hundredth percentile. It was on the 50th percentile before. We don't totally understand what's going on, but for a lot of people there is a benefit in that. So I, I, I picked on that. I said exercise and nutrition and sleep. I picked on that because I think this is something that targets aging. And I, I do agree with you that at the end of this fasting you have to make sure that you have a lot of proteins. But I'll tell you that proteins in elderly are also the enemy because they activate this MTOR pathway. That is one of the holy grails for us of how to stop aging. That's rapamycin.

It's tough too, because this is one without. You know, Peter has a strong view that you also increase MTOR with exercise. And exercise is good and we're still. We know that, like, exercise is absolutely good as you age. So if exercise increases mtor, you know, it's. To me, it's. It's interesting. I understand both sides on this. And. And what is my takeaway? You should exercise.

Yeah, look, your takeaway is good. I think you have to exercise at any age. And as I said, there are trades of. But if even. Exercise is not only about the muscle. Right. It's about the brain. But people who exercise have less Alzheimer's too. Right? So it's about the brain. It's about your immunity, it's about your stamina. Right. So exercise is a geroprotector. Okay. Not a general therapeutic. The therapeutic or fda. Right. It's geroprotector. It's number one. It's good at any age. We have no doubt about it.

So you mentioned biological age. In your view that there are a number of tests on the market that. That one can go get, or what's your view on some of these tests out there? Are there any that are better than the other or how accurate are they? How should we be thinking about these tests?

There are many tests. I took 10 of those tests. And so I'm between 20 years younger than my age to three years older than my age. Okay.

Wow. It's like getting a quote from a contractor. You're doing work in your apartment, in your home, and you get all these quotes from a contractor and you say they're all so far off, I don't know who to trust.

Right. But listen to your country. Your contractor says it'll be ready by May and you have to ask each year. Right? That's. That's the point. So.

So yes, I live in Miami. That's a real question.

It's like that. And you know, I would say it's like the genetics. I think this information is probably important. Important. And. And maybe this information. Look, my last paper was in nature. Not. Not my last. It was like one of my last papers were in nature where we took 5,000 biomarkers in thousand individuals. Right. And we asked what changed between the ages 65 and 95. That. That wasn't the last paper. That was the paper before last. It was in nature. Medicine in nature. We basically showed that we know which proteins that we measure in the plasma, in the blood are coming from which organ, which come from the brain, because it's breakdown. Right. Mainly which comes from the brain, which. From the kidney, which. From the liver. And I will tell you that they are all related to each other. In other words, 80%, you take the whole proteins of the whole body and most of the organs are related to them. If you find the age of the body, you found the age of the liver or the kidney or the brain, but 20% are not. So, for example, we have people who are slow agers, okay? They are actually their age is younger than their chronological age. Their biological age is younger, but their brain age is faster. Or maybe their liver age is faster. What does it mean? Maybe it means that this organ you have to watch now, maybe this is where the disease is going to come. Maybe your liver has fatty liver in it, right? So things like that. So what I'm telling you, we're trying to have a resolution to understand those hallmarks are telling us what exactly? Because maybe they're telling us about our brain or about our immune system or about our muscle, okay, Many maybe each one of them. And in fact, some of those two of those hallmarks, one has to do with my, the one that I'm youngest is to do with my mobility, and one of the youngest that I'm 10 years younger has to do with the age of my heart. Okay? So all those hallmarks are interesting. But you cannot. But this is not, this is only explanation. The point I really want to make. And that's another study that I'm leading though. What, what you want hallmark to be is not only tell you what's your age, but when I tell you your age and tell you to exercise, that I can see that this hallmark is improving, that you're becoming younger. Right? That's what I want to do. Just like with cholesterol, your cholesterol is high, will lower it. We know that, that, that has a good benefit. Those are the biomarkers. So what we're trying to do now, not trying, we're doing, we're taking studies that have been completed, completed already on gerotherapeutics and where us and within a year, a sample before and after. And so we're asking not only what's your age, but what have changed with the drug. Now every drug could change something specifically, but they're all changing aging. So we're going to learn about the drugs and we're going to learn about aging. And I think this is where the future has to go. What are the tests that are changing? You know, methylation, which is the common clocks that are being used, are not changed. They're not changed within a short period of time. Okay. And not all of them are changing in a short period of time. So maybe they're accurately predicting your mortality, but they're not helpful when you want to do something.

Right. And so if we come back to, we've talked a lot about the, you know, 50 plus or, or 40 people start to think about this. What if in my, I'm in my 20s or 30s, what should I be doing today that's going to pay huge dividends tomorrow?

You know, we, we commonly believe that exercise and nutrition and sleep and social connectivity that are chronically practiced have a very positive effect on the future. Okay. They're data that we quote and say that that's what it is, but for the future. And when I'm talking about the future, we talked about the date. You have to know the year. Let's look 50 years forward. So it's not relevant to us. I was talking about chronic intervention in lifestyle. And it's different at every age. Look, the young people, they don't sleep because they are at bar late or binge watching television. Okay? The elderly are not sleeping because they cannot fall asleep. So it's a little bit different in each age, but those are the things that we know. But when I'm looking at 50 years from now, I believe that what we'll have, when you're 20 years old, you'll get an injection every month or every few years, I don't know. That will basically erase this biology of aging from your cells and you'll be kind of Peter Pan for every young.

Wow.

And you'll repeat it and I think then.

So you think this is real? How, how far away? And just. I think this is a. How far away?

Did I say 50 years? Did I say 50 years? Because you cannot, I'm not the contractor, you cannot sue me on that. It's happening now. For example, my friend David Sinclair is a scientist in Harvard. I think you interviewed him.

Actually, we've had it. We've had David on a few times. Yes.

So he's doing those things in certain organs, like in the optic nerve. He can rejuvenate back. He can erase aging back in cells, in organs. So I think that practically it will evolve to treat diseases, but at the end we have to do it in our whole body.

And so we'll get to a place in 50 years where essentially you're saying people could live for hundreds of years. Are we going that far if we could essentially stop or is that how far we're going to go with this?

So look, a maximal lifespan for us as a human species is estimated to be 115 years. This is a statistical modeling.

Okay, 115.

115. We know that somebody lived to be 122, but we're talking about statistics. So we are dying on, you know, half of us are dying before the age of 80, so we have 35, 40 years that we can realize before we need to think of how we break that. Okay. I hope that we'll continue to increase life expectancy in the meantime and maybe rapidly. But there is a roof. So if you're asking me can we break the roof, and I say not today. But I'm not sure that it wouldn't happen in the future.

What I tend to think of. You mentioned the roof. I think of, I think it's Bannister, the four minute mile, where, you know, decades ago there was this view. You couldn't break the four minute mile, then suddenly it breaks it. Now everyone breaks the four minute mile. And what I see happening with the longevity or more specifically healthspan space in the last decade, there seems to be a mindset shift with many of the people leading the conversation who are resistant to this idea of aging. You know, I think culturally you used to think, you know, I got a case in the 40s or I'm just getting older. And now you see many leaders in the space. The Peter Attias of the world, the Dave Asprey's, for better or for worse. I think I love Dave, but he takes it way too far. They're resistant, they're saying no. And David, David as well. It doesn't have to be this way. And I can speak my own out of one. At age 49, I feel fantastic. And my labs prove that I'm doing much better than I was five, 10 years ago.

I'm shocked. You look 70 to me.

There you go, Walt. I'm doing all the, all the testings. All the, all the testing says I'm younger. Thank you.

You look great. Believe the test. Believe the test. No, you look great.

But I come back. No, but I think the thing you can't measure, it's a little bit more difficult. We've had. Doctor, we've talked about this on the show. You know, mindset and the role mindset plays. It's a little bit more difficult to study. But in your view, how much of that plays a role here where I have the view I'm not going to get old. I push back. I resist this notion that I'm going to get old and weak and die.

So we were exchanging emails this week about the term aging reversal. Okay. And somebody probably misspelled reversal. And what we got after the autocorrect was aging refusal. Yeah, And I like this term. I actually like it more. You know, I'm waking up in the morning, I'm seeing a mirror and I'm refusing. I'm not, I'm not. I'm a refusenik. I'm not going to age. I'm refusing aging. So I'm also on the council of the Healthy Longevity Medicine Society, okay? It's a medical society, so it has to be responsible. It's a medical society, it has to be responsible. And it teaches longevity doctors what's out there, what's shown to be true and what's not shown to be true and practice this medicine responsibly. But the really major point of this society, the revolution, is we have to spend time on our health rather than spend time on diseases, okay? If we spend time on our health, if we identify the biology of aging that can be reversed or stopped or delayed or refused. Let's use refused. This is really what we're trying to do, and we can make progress there. But like every new field of medicine, you have to build the evidence. I think the evidence is building, but we don't want to kill anybody on the, on the road to success. We really have to be. I want, I'm not a. Look in medical school the first day on medical school, they teach us do no harm, okay? So imagine on a curve, half of us don't want to do anything, right? You can come with whatever pain. I don't want to do that because I might do harm. And everything has trade offs. As I said before, by the way, the second day of medicine, they tell us there's no always or never in medicine. So not only you're conservative, you're unsure of yourself, okay? And this is paid for us until we come to an area like aging, okay? And people say, I don't know anything about aging. Well, we actually know a lot about aging. And we're telling you there are some drugs out there that are safe and it's legal for you to repurpose. So I really think that will drive more people to consider drugs. But you can consider drugs for a reason. If you're hemoglobin A1C is 5.8, you can take metformin or SGLT2 inhibitor or GLP1 if you're obese. Right. Or things like that. So I think we can make really real progress. But it'll be really helpful when the FDA is with us and saying, you know, hey, aging is something that we can target.

I wholeheartedly agree. And I think the repurposing of drugs is fascinating. We did a podcast a couple years ago. We'll link to it in the show notes with Dr. David Fagenbaum. He had some extraordinarily rare disease. He went from quarterback at Georgetown, looked like the picture of health, like an Adonis.

I know, I know. David is a great story.

And then wearing away, looked like he was ready to die. And he was in med school and said, let's try to figure this out. And I forget what drug it was may have been metformin or rapamycin.

It's rapamycin. It's the MTOR inhibitor.

And essentially cured his incurable disease by repurposing a drug that was available in every CVS in the market. And he's a fantastic guy.

I'm talking at 2 o' clock today with a woman. I don't want to say too much because. But she has a rare genetic disorder that I haven't heard on before. But so all her family is affected and one of them was on metformin and it cured him. And now everybody took metformin and it cured them. Okay, so those gerotherapeutics that have, you know, lots of stuff going on are potential treatment of some things that we didn't know before. So. But I want to say something, I want to say something about nutraceutical because I don't want to forget that. For me, the troubling nutraceutical is that a lot of people who are producing nutraceutical would love to do clinical studies, right. And give it to control, give a placebo and the drug and have some outcomes that are measurable. They would love to do it. But if they do it, the FDA will not allow them to put on their drug. You know, in clinical trial it did X. And I think that's a really obstacle for us. I think the FDA should have two parts for nutraceutical. One is whatever it's now, and one is for people for companies who did at least phase two kind of trials that showed statistically that something has improved. Because we need some help in getting through the, the, the fog here. And, and I think that's very necessary.

I wholeheartedly agree.

I have to give you this example. Mars candy bar, right? Mars candy bar. Mars spend huge amount of money to study 20,000 people that half of them got flovenoi chocolate in a powder and half of them got the same taste powder but without the chocolate. And in 3.6 years. There was significant improvement in cardiovascular disease, stroke, overall mortality with the chocolate. But mars cannot go and put on their candy bars. This is shown to prevent cardiovascular disease

as they should not be able to.

Yes, but, but you know what I can say now if somebody says chocolate, I can say there's a clinical study that showed that chocolate has actually significant effect on health.

It's definitely. The FDA has a lot of opportunity to say the least. And I think the pharmaceutical conversation is a tough one because I think most people would agree that without going down the rabbit hole of the flaws within our western medical system that many people are over prescribed. Doctors don't have time. They walk in, I got high apob. Well, here's a statin and there's no talk of lifestyle potentially before you, you go there and we, we need to get to a place where we're a lot more targeted with pharmaceuticals. And I think the repurposing conversation is so interesting for the David Vegenbaums of the world or in the context of metformin, where here's a drug where there's a lot of good. And I believe that it's, it's the marriage of lifestyle modification. To your point, we started with genetics. My lifestyle, given my gene set because I want to under. Your genes are not your destiny. We have the power to turn on and off genes and how they're expressed. Lifestyle can maybe only get me 70, 80% in some cases 90% there. But to get the extra 10, 20, 30, 40%, I'm probably going to need a pharmaceutical intervention. And that's where we're going. And that's exciting, correct?

You said it better than me and I'll adopt your words now.

So we covered a lot today. Is there anything we didn't want to touch on, you would like us to cover or any words of wisdom or anything you'd like to share with the audience?

Before we part, I'd like to say one thing. You know, we're talking about us and our interested and our age. But there are other people that need help. Cancer survivors are aging rapidly. After all, we give them chemotherapy and radiation. We age them, they need help. And they're young. You know, their children who survive cancer can get heart attack when they're 35. Right. So they need help. I should also say women with breast cancer. Okay, who else? People who have HIV, they get diseases 10 years before their cohort. People are disabled. Right. They're aging fast. Poor people, you know, poor people in every city die 20, 30 years before rich people it's more complex because they're not going to do the environment that they don't like fish and they don't go to the gym. And if we want to go to the moon, we're to Mars. I'm sorry, we're not going there if we didn't stop aging because we're going to get cancer or heart disease and we're never going to get back. So there's a lot of reason beside our age to start thinking about it more seriously and implicating and studying it more seriously. The other thing I want to say is that women have major aging advantage of men in the United States. They live four years longer now. When we give drugs to female animal and male animals, some of those gerotherapeutics, they have effects. Some of them are good for males, and some of them are good for females only or mainly. So the biology of aging in women is actually very important because it's different than men. And four years is a lot, is a lot of life, you know, because even if we cure all heart diseases today, we're not expected to live more than two years later. And women are already four years, living four years longer. So we have to remember that the biology of aging by sex is very different. And it will be highlighted because we need to choose the right drugs for the right sex.

Well, as the only male in my household, I think it's clear to me that women are just superior. So I'll close there.

Me too. And I got permission from my wife to say that.

Thank you so much.

Thank you.