Mayim Bialik's Breakdown - David Sinclair: Reverse Aging & Extend Your Lifespan

Episode Date: September 9, 2021

David Sinclair (biologist, Professor of Genetics at Harvard Medical School, and author of Lifespan: Why We Age and Why We Don’t Have To) discusses ways we can extend our lifespan and the work he’s doing to slow and reverse aging brain cells. He details the best lifestyle changes and emerging technologies available now to prevent most diseases until our 80’s, increase longevity, and even reverse the effects of aging. David opens up about his mental health struggles stemming from his own insecurities and frustrations with the planet, how his mother’s passing changed his outlook on life, and the dream he had that influenced his research and became a turning point in his career. After debating about intermittent fasting, Mayim and David examine the thread between solving problems in medicine, economics, and sociology, the effects of stress on the aging process, and mental health components tied to the aging brain. Mayim considers the amount of resources needed if humans lived longer, and the impact western culture’s attitude about aging might have on an increased lifespan. David Sinclair's Book: https://lifespanbook.com/?utm_medium=social&utm_source=linktress&utm_campaign=get%20the%20book BialikBreakdown.com YouTube.com/mayimbialik   Learn more about your ad choices. Visit megaphone.fm/adchoices

The molecules we're developing that the drugs mimic the benefits of fasting and mimic the benefits of exercise. We give them to MISC and they become super fit and healthy and run 50% further on a treadmill. They get their vision back if they've lost their vision. If it's cheap enough, which is what I'm working towards, then, you know, why couldn't everybody be put on that after age 40? Hi, I'm Myambiolic and welcome to my breakdown. This is the place where we break things down so you don't have to. We're going to break it down for you Because you know she knows a thing or two

And now she's going to break down We're going to break something down today That you don't want to Because I didn't want to But first, let's meet the person who forces me Toe talk about the things that make me cry Jonathan Cohen Hi, Maim, hi everyone, you're welcome

Boy, do we have an episode for you today? We sure do. Who are we talking to today, Ma'am? We're talking to, well, first of all, a tenured professor, which is already like a very big deal. We're speaking to David Sinclair, Ph.D. He is, well, he's born in Australia, so his accent is really awesome. He is a professor of genetics at Harvard Medical School. And his specialty, his raison de etre, is reversing aging. He's published over 200 scientific papers. Like he's the real deal.

But he wrote this book called Lifespan. It's a New York Times and international bestseller. It's been printed in over 20 languages. Lifespan, why we age and why we don't have to. And before you think like, oh, this is going to be some book about like, you need to exercise more. Nope, it's very, very not that book. This is a very scientifically evidenced-based book with a lot about research.

and the science of what aging actually is and a very, very, I mean, I don't even know the adjective, it is a phenomenal proposal about something that really sounds like something out of science fiction. He presents a very reasonable and reasoned line of thinking, I don't know what to call it, that proposes that we don't have to die when we do and we don't have to age the way that we do. And Maim gets extremely, extremely upset. This is an episode you need to listen to the bitter end, meaning, I know some of you, I know what you do. You listen to the guest, and then you're like, okay,

you're going to want to listen to this entire episode. There are many things that we know lead to aging, right? I'm going to just rattle off a couple from his book. You know, things like genomic instability caused by DNA damage. Attrition of the protective chromosomal end caps, which are also called telomeres. Alterations to the epigenome that controls which genes are, turned on and off. And all the cool kids are talking about telomeres and epigenomes.

They're also talking about mitochondrial dysfunction. They're talking about zombie-like cells, which I just love that that's an expression. Stem cells, the exhaustion of stem cells, and altered intercellular communication and the production of inflammatory molecules. And you might be like, I knew that. Well, turns out those hallmarks of aging don't have to be as such. And he discusses epigenetics, which is something that we've mentioned. here and that a lot of people talk about. And I mean, he walks you through from like the cell up. He really does. It is not for the faint of heart. Something I do want to mention before we welcome him. There are some simple tests, this is a quote, to determine how biologically old you probably are.

The number of push-ups you can do is a good indicator. I have a shoulder problem. I can't do very many. You're old. That's what he would say. If you're over 45 and can do more than 20, you're doing well. and I believe him because he's a doctor. There's also the SART, that's right, the sitting rising test. Sit on the floor, barefooted, with legs crossed. Lean forward quickly and see if you can get up. I'm barefooted.

Oh, she's doing it. Look out, SRT coming at you. She's getting down from her desk. I can barely get down on the floor. Her back has been out for three weeks, and now she's going to do this standing test. She's on the floor. I can't. She can't get to her mic.

I'm going to narrate for you. I'm sorry. Okay, so hold on. What am I supposed to do? Now you're supposed to get up without using your hands. Totally not true and never going to happen. Sit on the floor, bare foot with a line. Lean forward quickly. Even that can't happen.

See if you can get up in one move. A middle-aged person needs to push off with one of their hands. I'm elderly. Okay, let's see. I'm sorry. Mine is going to lean forward and get up quickly. Like this? She's holding onto the desk and pushing up with one hand.

I'm pretty sure she's cheating. Now she went up to one knee. Then two knees. She's both middle-aged and elderly and needed a desk. You know what we just discovered? I'm dead. And with that, it is a real, real honor to welcome one of Australia's leading scientists under 45 is one of the awards. He's gotten a medical research medal, the Merck Prize, the Genzyme Innovation Award.

I just want to say Genzyme over an overall. He's also gotten the NIH director's pioneer ward. Time magazine has named him one of the 100 most influential people in the world and one of the top 50 people in health care. This might be one of the most impressive people we have had on the podcast. It's a real honor to welcome him, but Jonathan, you want to say something before. Well, Maim has a lot to say during this interview and she questions him. She questions a lot of the big assumptions. Oh, I poked the bear.

That's a very polite way of saying what you, do in the first half of this interview. The second half of the interview, we get into really the nuts and bolts of his thinking and he really opens up. And he shares, I've listened to a lot of his interviews on other podcasts and he shares in a way on this one about his personal life that I had never heard before and I was truly moved. And the context that I want people to go in with is that from my perspective, it takes people like David Sinclair to push the boundaries of what we believe is possible. And that he does. I push. the boundaries of what everyone thought was possible for a podcast host in this episode.

With that, let's welcome David Sinclair in what we would like to say is probably the most personal interview that I think he's done. Break it down. We're really, really thrilled to speak with you. Your reputation precedes you in all of the best ways. We're really, really honored to have you on. And Jonathan in particular has been talking about you for quite some time. And so we were really, really excited.

to tear through lifespan, as it were. We have a bunch of questions. And, you know, I think where maybe we can start is, you know, our podcast obviously leans towards, you know, mental health, mental wellness. And, you know, there's many aspects of aging that touch that. So before we kind of get into more of the particulars, maybe you can speak a little bit to what you see

as some of the sort of mental health components of the way we approach aging, either as scientists or even just as a society? Well, aging definitely changes the brain. It changes our ability to not just remember things, but perceive the world. And the aging brain is quite an interesting thing to work on because the question is, what is going on with age in the brain? What is causing it to malfunction? We take it for granted that aging happens, but just because it's common doesn't mean we understand it. And what we think goes on is that the brain is forgetting how to be a brain. And what we're working on is ways to slow that loss of identity of the cells and even reverse

it. So the cells in the brain wake up and remember how they're supposed to function. And that's what we're working on mainly in the lab. But I talk to a lot of elderly or older people, as we should call them now. And there are two camps. There are those who are sick or frail and generally are not looking forward to the future. But then there are those people who have managed to, whether it's their genes or the way they've lived, stay healthy. And then it's a completely different story. I made people in their 80s and 90s who were just as excited about their daily lives as they were when they were 20 or 30. A lot of my work, both just as a human, as a parent, and as someone who's a scientist, but who dealt really with like, what are people like now? You know, like, I studied

obsessive compulsive disorder. Like I'm very like what's your behavior like today and I'm not thinking about later. But one of the things I've tried to be an acceptance of and I feel like is a hallmark of my ability to function as a human is that we're going to die. And it's going to likely be tragic and sad. But I need to be present and I need to enjoy the time that I have and do my best. You know, like, I've also, I've been a caregiver to two of my grandparents in particular as they reached the final stage, it's actually three, of their lives. Like, I've witnessed death. I've been a caretaker in those stages of death.

My father died over a prolonged, he had multisystem atrophy, like years and then 29 days of waiting for his body to say no more. What you're proposing is a real paradigm shift in that, I've spent my, most of my life just trying to be like, oh my gosh, I'm not going to live a long time. And like, I'm already on the end of what I'm here for. How do you propose a reframe? Like, was Buddhism wrong? Like, is it all wrong, David? Yes. So I like to look back in time as well. Let's go back to just 200 years ago when people would not generally make it in a healthy way post about seeing. And a lot of people died earlier than that from disease.

Is that a better life? Would you want to go back 200 years and live then? I don't think so. And so the same will be true in possibly within our lifetime when people can live an extra 10 or 20 years in healthy way. And they can play tennis when they're 90 or 100. Then that doesn't make life less worth living. I think it would give us even more excitement about being alive.

Let's say I can make you live a thousand years. I don't want to live that long, David. I'm so tired. No, I'll give you the energy as well. And you'll be healthy and you can have different careers. You want me to live a thousand? Nobody wants me to live a thousand years. I do.

You got lots more to do. You're just getting started. But if you live a thousand years, why would you want to die tomorrow? Nobody who's healthy who has friends wants to die tomorrow. There's never been a case. Okay. I'm going to go ahead. answer that. I shouted at your book many times. I'm just going to say it. So I hope you have a good

sense of humor because this is what your book made me feel. This is what it made me feel. We don't have enough resources. And you cover this in your book. So I'm not saying that I stopped reading when I was shouting at it. As it is right now, we don't have enough resources. We are killing the planet. I mean, we're, we are hurting our planet in ways that have significant impact already. One of the pieces that I feel maybe could have gotten a little more emphasis is that many of the things that ail us are socioeconomically related largely to access to food and nutrition. Those problems exist even if we're all living a thousand years. And you, you have a very beautiful analysis of what it would look like, again, this paradigm shift to say,

all these things be, I mean, you made every point that I did, that I was making, and then you really do. You have a proposal for kind of what it would look like, but how do I reconcile that? When there are people in the city that I live in who cannot eat or feed their children, the the epidemic of mental health crisis has made it such, I mean, to be specific about mental health, that the people who most need access to help simply to do the basics, be employed, pay rent, feed their children, have childcare so they can work.

Like those things weigh on my heart. That's just the kind of person I am, right? So it's very hard for me to go on your experiment, your thought experiment with you. Right, but come on this journey with me. You've got to change your view of the world, not just at the individual level or even society. You've got to think globally.

What would happen if, on average, people didn't get sick until they were 90, or even just 84? Okay, but how about the second I had children, my body started dying? I mean, like that, but that feels true. to me. Meaning, I have a hard time making even that leap. Because what I do say, and this is as a woman who gave birth to children naturally, breastfed them for 86,000 years is what it felt like.

Like, my body, once it cranked out a human, it was like, we don't need to fix things anymore. Oh, you sprained your ankle. How about four years where you can't step on it right? Yeah, well, that's the problem. That's what we want to fix. Your body shouldn't just give up. It should fight against diseases. This is what we call it. whole medicine. All I'm doing is taking a different approach to slowing down and curing diseases. And no one's ever said curing diseases is a sin. I just might be able to do it across the body rather than just put band-aids on one organ at a time. And I think that's the best way to improve people's lives is instead of keeping one part of the body healthy like the heart and letting the

brain age, that's cruel. Why don't we keep all parts of the body young? And that's what we seem to be able to do right now. My NBialx breakdown is supported by Superpower. We all know the feeling of leaving a doctor's office and kind of feeling like we didn't get anything out of the experience that was useful. Maybe they're like, you're fine, drink more water. There's no real data. There's no game plan. This has happened to me many, many times, especially on the perimenopause journey. That's why we're fascinated by what Superpower is doing. They send a licensed professional to your home or you can visit a nearby lab. One simple blood draw with over 100 biomerase. That's way more than you usually get.

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And the people on the street who need help, the reason they're not getting help is because there's not enough money to go around. Right, right. I would argue there's plenty of places I would like to take from celebrities and overpaid, you know, sports stars is one of them. I'm a biologist, so that's out of my jurisdiction. But what I can do, and I'm hoping to do, is to save the U.S. $86 trillion. We've calculated that just one of the medicines that we have at our disposal, it's actually, already on the market, known as Metformin, would save the U.S. over a decade, $86 trillion. And if you do it for the entire lifespan of this generation, it would be $360 trillion. You can do a lot with that money. I don't know. You're a biologist. You're talking like an economist right now.

Well, I got friends for economists. That's where I come from. And they tell me, this is a good thing for the planet. So we can save ourselves, and in doing so, save the planet as well. David, tell us a little bit about metformin. So metformin is a slight chemical variant of a molecule that's found in the French lilac. So it's pretty close to being a natural molecule. And what it does, it was found by accident, is it improves and reverses type 2 diabetes, which is having high blood sugar, which we all know is bad.

It leads to accelerated aging and heart disease and eventually death. So it's good to keep your blood sugar levels below what's a number. which is the number five. And also, type 2 diabetes is not the kind that people are born with, meaning type 1 is the kind that is congenital, as it were. Type 2 comes from... We actually think that the reason type 2 diabetes occurs, as it does if you don't exercise and eat well and eat the right things, is because aging is happening more rapidly.

So here's the point. Aging is the main cause of all the major diseases that afflict us. We have to get away from the idea that type 2 diabetes is called by X. and Alzheimer's is caused by Y and heart disease caused by P. It's not the case that these diseases don't happen to young people generally. They also happen very rarely to people who don't eat lots of processed food, meat, and dairy. And yes, the more you eat, the more they accumulate in your arteries. That's true.

Yes. And about 80% of your health in the future is dependent on how you live your life. And only 20% is what you got from your parents in your DNA. which is really important to know because if you think, oh, if I just, you know, if I sit around all day and watch movies and eat popcorn, I don't have to worry. Well, you're really missing an opportunity to be healthy over the age of 70. So what would this strategy be with metformin? How would it be rolled out? Like, what is the utilization?

Would it be for people who, like, I've heard that you are taking it. But like, how do you determine if someone is right for taking it? And, you know, like, how would it, you know, be implemented? Yeah. Well, so I'm not a physician, so I can say anything. I'm just a PhD with a big opinion. And my opinion, scientific opinion, is that this is an extremely safe drug. It's not perfectly safe, so you need to ask your doctor. But it's one of the safest drugs in the world, and it can have huge benefits. It's been shown in multiple studies that if you look at tens of thousands of people

who take metformin for their type 2 diabetes, they, on average, live longer and a health than people that never had type 2 diabetes. That's compelling. And the FDA is excited about this data, and they want it to be proven by doing a prospective study. You say that like it's a bad thing, David. You said proven like it was like, oh. Yeah, well, sometimes it takes a long time to prove something.

We know what's going to happen if we don't do anything, right? We're all in denial, but let's just face it. If we don't do anything in 30 years, probably I'll be gone. So what's the harm in taking a pill that costs me less than a dollar a day that's not going to hurt me? My doctor says it's okay, but it might make me live another five or ten years. What's the mechanism of metformin? Well, it's debated. One main mechanism that's somewhat agreed upon is that it inhibits the body's ability to make energy. And in response, the body starts to make more energy.

It's a mitochondrial dance partner, as it were. Yeah, yeah. Let's talk about the other things because on page 304, you list the things. And, you know, it's funny because you put it in the conclusion, but I think it's important. I do think it's important and I'm glad that you included it. So you have a little list. So you take metformin daily and you also take NMN. So tell us what NMN is.

Well, the full name, if you want to hear it, is nicotinamide mononucleotide, but it's just a small chemical that the body takes in as a vitamin and turns it into a really important chemical in the body called NAD. Jonathan loves NAD. He loves it. Well, everybody should love it. Without NAD, we're all dead in 30 seconds. It's really important.

It's the molecule of life. It carries out hundreds of chemical reactions in the body. But what we found is over time, the levels decline. If you measure the skin NAD levels in a 50-year-old like me, I'm 52, they would be half the levels of when I was 20, which is not good for metabolism and enzymatic reactions in the body, but it's also bad because NAD is required for the body to defend itself against aging. I have a question about, is there a benefit of taking it in NMN versus NADH? I take the NADH in a liquid form.

And a shout out to all the people, like this came up in our Kelly Clarkson interview. She started listing off stuff. I'm like, this is right out of the David Simclair Playbook. And she's like, yes, I know. We do not prescribe medication. We cannot give recommendations for medication. Do not message me on Instagram asking me for what brand we are not sponsoring any sort of supplements here, people. Just FYI.

Is NMN a precursor? Is that? Is that why you take it as NMN versus NADH? Yes. So NADH and NAD are larger molecules. And NEMN is a precursor building block. And it's small enough that it does get taken up into cells. And so that's why I take NEMN.

We've tested these side by side, which is what a good scientist should do. And so far, NMN is the winner. And what's resveratrol? It's the molecule in red wine that went around the world when we discovered it was important for aging in 2003. Do you drink? I drink every night, yeah. Oh, that's the sound bite right there. I drink every night.

I would say because I only eat one meal a day, probably a third of my calories are alcohol at this point. We'll get to that in a second, David. Okay. We've got the NMN. That's the precursor we talked about. Smaller molecule. Jonathan, I'll explain it later. He's going to ask.

Resveratrol and your metformin. You also take vitamin D, which is like one of those powerhouse vitamins. That's the one you get from the sun, but you can also take an absorbable version, right? I take liquid. It's very important. It affects a lot of things. Vitamin K. you take aspirin, so that's very old school and totally kosher. You try to keep your sugar bread

and pasta, as Jonathan pronounces it, intake as low as possible. You gave up desserts at 40, but you steal tastes. I'm digging this. I'm going to skip skipping meals, because we're going to get to that in a second. Then you say every few months, a flebo comes to my house to draw my blood, which I have analyzed for dozens of biomarkers, and you moderate those. And that's a little more complicated and sophisticated and something that a lot of people may not have access to right now. But in the future that is David Sinclair's future, everybody gets blood drawn every time you wake up, you just blink your eyes and numbers come up in front of them. You say, I try to take a lot of steps each day. You walk upstairs, you go to the gym, that's great, you hang out in the sauna

before dunking in your ice cold pool. That sounds delightful. Also very good for you. You do talk about the value of cold. And I know some people who've done the cold shower kind of challenge. and they say it has absolutely changed their life and vitality. So you also are a fan of cold, correct? No. I hate it, but I do it occasionally. It's not pleasant. I mean, the whole idea is putting your body into a state of shock, a bit of, we call it

Formisus. What doesn't kill you makes you stronger. Right. And actually, that was something that I highlighted. I like this. I eat a lot of plants and try to avoid eating other mammals. They appreciate that, even though they do taste good. All right.

and you don't smoke. You say, I try to avoid microwaved plastic, excessive UV exposure, x-rays and CT scans. That's a bummer because sometimes Jonathan needs those, and now he's going to be like, David Sinclair says I shouldn't take this x-ray. You say I try and stay on the cool side during the day and when I sleep at night.

You try to keep your BMI in an optimal range. I've got some BMI issues, but okay, we take that. Let's talk about the skipping meals. You absolutely have the street cred and the academia cred in that. I don't believe you're trying to sell me a diet or, you know, a way to lose weight. The reason that I took a little bit of pause with that is, you know, both as someone who has a mental health podcast where we talk about eating disorders and disordered eating. And I myself happen to be a person

who uses the 12-step program of Overeaters Anonymous to manage a lot of disordered eating that I have. I've met a lot of people who talk about lately intermittent fasting. And I recently this summer interacted with a woman who only ate for two hours a day. She only ate for two hours a day. And she was, I think, mostly motivated by a desire for weight loss. And as a human being, as a mother, and yes, as someone who has a little bit of science training and went through biochem, I cannot imagine someone. someone trying to rationalize eating for only two hours a day because the word that I call that

is starvation. So I understand that there are mechanisms that your body will take on often as compensatory mechanisms. But it's hard to not think of this kind of intermittent fasting, forgive me, as a bourgeois trend. You can think that. The science is very, is very, good on that. It's not so much what you eat. It's so important. It's when you eat. And the body responds well to periods where it's not filled. That's called when I sleep, David. Well, yeah. So the idea is to extend that by one meal or so. So skipping breakfast or skipping dinner has undoubtedly health benefits for most people. Now, I'm not talking about malnutrition or starvation. That's absolutely not the case. I am an overreater. I was borderline obese,

of my childhood. I've struggled with my weight my whole life. But through sheer willpower, I've gone down to having a very enjoyable one meal a day. Do you encourage your children to eat one meal a day? My children, of course not. Okay, so, okay, hang out one second. So at what age would you like me to stop eating three meals a day? I mean, I'm a vegan. I eat all day because I don't have anything that sits in my intestines and gut to kind of keep providing fuel. So every two hours, I give it a little top off. You know, it's like human breast milk gets metabolized every two hours. Just keep it coming. Yeah. Well, I mean, that's fine. I'm just telling you the science. I'm not trying to sell you any diet here. I'm not trying to get your goat. I do think that there's a special

sensitivity, like I said, that I have when I hear people say, I'm only going to eat one meal a day. And the fact is, you know, I mean, again, the interest that I have, you know, honestly, in you and in this book is how many beautiful threads you do weave together. Because you're absolutely right that having people solve one problem is not the way to do medicine. It's not the way to do economics. It's not the way to do sociology either. So I really, really love that. But I also want to have, you know, the Sinclair View, you know, incorporate other components. of people's existence, which is, you know, God doesn't care about what I look like.

God doesn't care about a number on a scale. Like, I need to have a healthy relationship with food. And for a lot of people, that's going to trigger a lot of shame and guilt and restriction. And, you know, do those people just die early? And the only people who get to live a long time are people who don't have eating disorders? Well, I'm not perfect. I find it very difficult not to eat. I also don't like exercise. I don't like the cold. And the fact that I can do this, and get to this point. It's not easy. I'm not saying you can do this tomorrow,

and I've been working on this since I was in my 30s to get to this point. So when would I start? You asked me, well, there's no science as to when the best time to start is other than the earlier, the better if you're a mouse or a rat. That's what the data says.

But I wouldn't want anybody as a teenager or perhaps even in their 20s doing this. They have already their, their longevity defenses are up, you know, maximal. But once you start to get into your 30s and definitely by your 40s, your body's starting to slow down in its ability and desires to defend itself. And our lifestyle is what is making it worse, sitting around, eating whatever we want, not moving as much, not experiencing temperatures that are out of our comfort zone.

All of this is conspiring to make us frail in our 70s and 80s. on average, you don't have to have a life like that. And I'm just saying what the science says. Let me tell you a scientific fact. If you take 10,000 mice roughly, and you give them different combinations of protein, fat, and carbohydrate, and you split those groups into another two groups, one that eats whenever they want and one that eats for a couple of hours a day,

the only group that lives significantly longer is the group that eats for two hours a day. I know we're not mice, but to me, that was that, for me, the clincher, that it's, we're worrying too much about what's in our food instead of worrying about when we should be eating or not eating is the case. And calorie restriction, as we used to call it, is the most robust way to extend the lifespan of any animal, even a yeast cell. When it's calorie restricted, it'll live 30% longer. And so intermittent fasting is just an easy way, I find, to eat fewer calories. If you never have sex and you have it once, a year, yeah, I mean, I would say there's a certain enjoyability. There's also, for me,

it would be a tremendous amount of anxiety. Like, if this meal doesn't go right, if this sexual encounter isn't everything I've been waiting for it to be, I'm going to be very, very sad. And then how am I going to eat my feelings if I don't get it in those two hours? You'll have a lot of time for journaling and with all the time you save from not having to prepare food and look at Uber Eats. I got a thousand years of journaling waiting at No, you're looking at it the wrong way. Even mediocre sex is fantastic if you're deprived. It's like pizza.

It's like even when it's not so good, it's pretty good. And did you try to like have lunch and dinner? Like how did you decide it was one meal a day versus two meals? And do you think that has a significant difference? Well, I go what the science says. I'm only science driven. Nothing else to drive me. And I've just read thousands of scientific papers.

And then I test stuff out of myself because I'm curious. and what has worked well is to get down to one meal a day, and I've never been healthier both on the outside or the inside. And did you have a hard time transitioning to that? Like, did your brain function? Like, were you caffeinating during the day? Because some people, for me, like, for example, it's a little hard to kickstart myself.

You know, I can go to like 11, 12 o'clock, but until I have a meal, I find it, you know, challenging. Well, it's hard. No one's saying that what I have done now is easy, but it is easy for me now. In fact, if I go back and I start eating a big breakfast or lunch, I feel sick and I lose energy and I'm sleepy. But to get to this point, it's taken years.

And the first few weeks of not eating lunch, they're really hard. You say something really, really interesting about health care, you know, that we have the capacity to be beneficiaries of medical breakthroughs that would be subsidized and produced. I mean, like, that's something that could exist. And you said that people in the United States are not, we're not having access. to that. You say Australians are, Britons are, as are the Swedes, the Dutch, the Irish, and the Slovenians. They're all benefiting in terms of lifespan and health span because they have the sort of universal access to health care that, and then I'm going to paraphrase, most people in the United States don't believe in. So can you speak a little bit? Because this was, you know, one of my most

favorite parts, you know, like I said, of your thinking and of the way that you present information. There's a lot of pieces to this. Can you talk a little bit about health care and where that falls into the kind of, you know, forward thinking that you're doing? Well, I was born in Australia, so I know what a country is like where you don't have to worry about falling through the cracks. In Australia, you'll never be extremely poor. You'll never be hungry. And if you're sick, you can be taken care of. That's a very different society to live in than this one in the United States, where you really can fall through the cracks.

be broke, be hungry, live on the streets. It's really quite a scary thought and a reality for a lot of people in the U.S., which blew my mind when I first moved here, 1995. I moved to the United States thinking almost everybody was good-looking, tall, war cowboy hats, had guns, and were super rich. Everyone was rich in the United States, and I arrived. Were you in Orange County? None of that was true. None of it was true. I mean, there are good-looking people, but there are a lot of people who are not doing well. And I thought, wow, that's really, it's a different reality than what we grow up thinking,

because in the movies we see a lot of wealth. And it's only gotten worse from there. You know, the United States used to be a lot richer than Australia. Now I would say Australians are richer than Americans overall. But on health care, it's a sad state of affairs here where we have this, we, you know, collectively, have this view that if you don't earn it, you don't deserve it. And not everybody can have a lot of money.

Economics just doesn't work that way. So you have to take care of the underprivileged, the people that might have mental disabilities that can't keep a good job. A lot of the homeless people, of course, have mental issues that they have to deal with. And in this country, in my view, we don't take enough care of them. Instead, we watch people collect a lot of money

and just hope that they're generous and that's not always the case. It's usually not the case. I mean, you just made me cry because, like, you know, I also think about, like, the problem is very large. You know, my father of Blessed Memory was a public school teacher.

And he, you know, my parents devoted a collected 70 years of their life to being, you know, being the caregivers for children in Harlem and in the Bronx. My mother taught in a women's prison. You know, like they were public school teachers. And they did not make

enough money to support, you know, even a, you know, what some would consider a middle-class lifestyle, right? And, you know, the health care that I had, I'm very, very grateful that, you know, teachers unions provide teachers with health care at all. But I grew up in a system where you didn't have the same doctor every time. Nobody knew who you were. You couldn't get an appointment. You couldn't get specialty. You couldn't get, I mean, most people can hardly get really any. anything. So the notion, I mean, so I have to say, like, I don't mean to overwhelm you, you know, with the problems of the entire country, but, you know, you kind of took on the whole world and the future. It's very hard, and this is something I think that Jonathan really, you know,

he and I are very different and he, we clash about this a lot, because sometimes it's very hard for me to frame myself in forward thinking when I'm so fixated, you know, on the kind of day-to-day crises that's so many people deal with. And I mean, forget about globally, like even if I just look, like I said, in my city, you know? Well, I always think that the solution to these problems is in part technology to make things cheaper and more available. In the same way that I love talking about London of the 1840s, where it was a city that no one would want to live in now. It was dirty and filthy and poverty and horse manure everywhere. And if someone had said, oh, we're just going to quadruple the population of London,

people would have said it's hell on earth. But in fact, London's a pretty good place to live in now, even though it's a little expensive. Once you pick feces up off the floor and you start vaccinating people, it's amazing what happens. Yep. So I see a future that's brighter that these technologies that I'm helping develop will be cheap and available to everybody, including those who cannot afford expensive drugs. And something like metformin or something even more powerful than that could be taken every day by someone who cannot get on the treadmill

or who does not want to fast. The molecules we're developing that the drugs mimic the benefits of fasting and mimic the benefits of exercise. We give them to mice and they become super fit and healthy and run 50% further on a treadmill. They get their vision back if they've lost their vision. And these technology, if they're a few dollars a week, that's a world that I would want to live in. I think that that if it's cheap enough, which is what I'm working towards, then, you know,

why couldn't everybody be put on that after age 40? Okay, I feel a little bit better. I'm not crying anymore. But what I also, you know, kind of balk at, and, you know, this is also because my grandparents were immigrants to this country. and, you know, my grandfather believed that these streets were paved with gold. And for him, from what he was coming from, this was the most he could imagine, you know, with his seventh grade education. This was paradise, you know? Like, this was it.

Working in a sweatshop was it. You know, my mother grew up in a tenement house. Like, to him, he was like living the dream. My fear is that rich people are going to have access, and already do have access to this. And there are many rich people who I would love to see live a long time. But I also would like to, you know, remind myself what I teach my children is that everyone has the capacity to be seen for their talents, their passions, and their strength. but if they are in a community that does not support even basic needs being met, we are missing out on an entire portion of our society and of people who don't get to live out,

they're human right just to be appreciated and loved. So those people are not the people who at this level we're reaching. So what worries me, with all due respect to you, David, is that we're going to get a lot of rich people, like, you know, living a long time. and like, look, I can cryogenically do this. And like, is that the first step? I mean, if you tell me that that's what's going to happen first, you know, then I can hang on a little longer. It's definitely going to trickle down if I have anything to do with it.

I'm 100% on board with what you're saying. I'm not trying to make medicines to keep rich people alive. I mean, there's a market for that, David. I'll tell you. I live in L.A. There is a market for that. Believe me, I know many of them. But that's not the point of what I'm living for.

What I'm trying to do is to make a medicine that's cheap enough for everybody on the planet to afford. Metformin is available over the counter in most developing countries, and it's very cheap. Everyone can afford it. Here you need a prescription and a little bit more expensive, as usual. But yeah, something like metformin, if I could make a drug that makes everybody healthier for longer and even cures diseases like heart disease and Alzheimer's. And I believe you can do that by reversing the aging process. And that would be a much better world.

And I understand your fears because technologies tend to be used by the rich and knowledgeable initially. And that's what we're seeing. But it's only just the beginning. This technology and knowledge has only been around for a few years. My book's been out for less than two years. But it's spreading. And a lot more people are learning how to change their lives, in part by reading my book. and listening to what I'm saying.

And then the medicines, they're in development. They're pretty exciting. And some of them should only cost a few cents a day when they get on the market. Where are you in that process? How far away? I know that's always a tough question. Well, the easy stuff is available. As I mentioned, there's inside tracker, which is a company that I use to monitor my health

and age. That's here. Then the drugs that are in development, I have a number of them in the pipeline. There's one that's true age reversal. That was the one that cured blindness in mice recently. What kind of blindness? Can you be a little more specific? Yeah.

So we created glaucoma, so pressure in the eye of the mice and restored their ability to see. And we also just took old mice that had become blind through old age and de-aged the eyes. We made the eyes young again. We now can do that. In my lab, controlling aging forwards and backwards isn't an issue. And then the mice could see just like they were young again. And it's a permanent reset.

We just do it for a few weeks and then they can see again. So we're working on muscle and skin and hair, among other things. We want to make a mouse live for another 10, 20 years, something like that. But to Jonathan's point, that technology is going into, has been in safety studies for over two years now. It looks really promising. And then the first human should probably be early 2023. We're going to try and restore vision to the blind. But there are other drugs that are more advanced.

We have one that's been in people now for two and a half years. This is one of these NAD boosting molecules. And we should know, I will know at least by the end of the year if it works. I'm not sure how much I'll be able to say immediately. But often people think this is science fiction for our children. It's not. These are drugs and there's at least, oh, I'd say at least 50 companies working on medicines that are like this. I have two mental health related questions.

The first is I'd like to know about your kind of mental health if you have a regimen or a set of practices that work for you or if you believe in therapy or if that's something you've partaken in. Yeah, let's start there. I was a child who was angry, depressed, insecure. That was up to the age of about 17. Then I became suicidal until I was about 23. And mainly that was driven by just frustrating. with the planet, frustration with being a potential failure and just being insecure. The reason I mention that is because it is possible to turn that around.

So through mostly work by myself, trying to read myself of negative feelings, read myself of my insecure self and only focus on my outgoing self. We all have those two in ourselves, I think. And then just be optimistic and focus on what's good about life rather than what's bad about life. How'd you do that? One big thing that changed my life a lot was I watched my mother die in front of me. She supplicated to death. And when you see that happen and you whisper in your mother's ear that she was the best mom you could ever have and just watch her choke, then every day after that is a good day.

So you have to, at least I had to witness the worst thing possible for a son to witness to realize that all this other crap that I'm worried about means, nothing. And so if nobody died today, it's a great day. If I'm getting up in the morning and I'm still breathing and the sun is shining, it's a great day. And everything else is just, you know, just get through it and work hard and you know it's going to work out in the end. So I've become, if people get to know me, they think I'm the most optimistic person they've ever met because I always start the day with good mornings, fantastic, sun shining, I'm texting my friends. This is going to be awesome. Can't wait to see what the day brings. But I, I, I, I had to work at that. I'm not naturally like that person. But it's a much better way to live

once you get into that habit. Do you believe that there are people for whom there is a certain chemical imbalance in their brain, which makes it, for example, significantly, if not clinically difficult to access, for example, serotonin, you know, dopamine resources, those kinds of things? Yeah, no doubt. I mean, I've had that myself. I've, I've, I've, I've, had trouble getting out of bed for weeks in my career. It's hard. And at the time, you think I'm never going to get better. Life's never going to be good again.

Yeah, I've been hit with real hard stuff in my life. But what it takes, though, is I find at least myself, I was able to fight those feelings and rewire my brain and get the serotonin going and feel good. But it took effort. It takes months of work. It's not easy. But you know, you just got to not be a victim and just realize that we have a limited time on the planet,

hopefully a little longer when I'm done with you. But we're lucky to be here. Ricky Dervais said, do you realize how unlikely it is that we are alive out of the billions of planets and the billions of eggs and sperm and the chance of us being alive here right now? it's an impossibility and the fact that we're here, let's not waste a single day because it's just precious. My other question regarding mental health. And, you know, I can't help but think of both of my grandmothers of Blessed Memory who struggled tremendously with mental health challenges.

We didn't call it that. It was just called being sad all the time because hashtag Holocaust, you know. So when I think about what their life progression was like, And when I think about what happens when you live with a pervasive sadness that depletes so many of your resources, because like that's a thing. I like to remind people, as the resident neuroscientist, there is no mental health component of your existence that does not have chemicals associated with it. You don't just float around having feelings. It's all the electrophysiological properties of every cell pushing chemicals through. there's nothing that just happens. When I think about what their lives were like emotionally, and in particular, being in marriages that weren't always supportive, which in those times,

it wasn't an option. It's who did you meet at English night school who would take you in when you were an orphan? Like that was literally sometimes how you got married, right? when I think about the things that happened over their, the decades of their life, I can't help but notice that the trajectory of their health would have been significantly different had they had more support. Can you speak a little bit about what we know is added to the aging process and the way that we recover, you know, the way we recover from things or, you know, my grandmother had three hip replacements in her life. And like, it was just like always bad and shitty, you know,

what does that do? Can you just speak a little bit to the mental health component of aging as, you know, as it relates? Yeah, we actually know or not a lot now because we can measure biological age with a blood test or a mouth swab. We're developing that. And now we can see not just how people look and how old they seem. We can actually tell you how old you are biologically. And when you do that, you find that people who had very harsh childhoods, for instance, the Dutch famine during the war in Amsterdam, those people are now programmed to age as they get older in their 50s and 60s.

And they get much more heart disease, for instance. Our cells are set up to control the genes. We call this the epigenome. And when cells get disrupted when you're young, it actually can accelerate the aging process. And so we've shown that we can do that in mice. We can make mice 50% older by disrupting this control system. One of the things I'm writing now, I'm writing another book is about how to protect your children and make sure that they have a really solid epigenome so that they won't be sick when

they're in their 50s, 60s and 70s. So nobody's talking about that, about how to protect children. But that's physical. So mental is also important. If you have inflammation in the brain, in particular, the hypothalamus, which is a small little base vestige of the brain that secretes a lot of hormones. Yeah, you know all this. Your listeners may not know the hypothalamus as much.

That seems to control the age of the rest of the body by secreting certain hormones. And if the animal is stressed, or probably if we're stressed too, we're secreting molecules like cortisol, which accelerate the aging process, puts us in a more inflammatory state. And it's very clear from just studying people who either have very calm lives and don't get stressed out versus those that are worried and have anxiety, their aging rates are very different. And so one of the best things you can do for longevity is to have a caring partner, and not have this chronic stress. Well, and I'd also like to, you know, again, not to be, I mean, I just like the bringer of doom here,

when you think of children in particular raised in war zones, and that war zone may be in Bosnia, and it may be in the Middle East, and it may be in the projects. You know, you are incubating, you know, communities, and we have. We have communities and populations who are all. being taxed and traumatized this way, it's profound. And I think of how much I want to shelter my children from knowing that this exists, right? Because my children, I mean, I say to them, you are privileged, you're entitled, like I'm going to Google things on the internet every time you complain that you didn't like

where we ordered in from, you know, today. But I think it's important for us to, like, we have to live with all those things. I feel like I'm going to depress you. This will be your next book. I was fine until I spoke. The myambialic, and then it all went in the shitter. No, but the fact is, I think it's important, you know, it's important to acknowledge that there are many other forces,

and we all need to kind of work on all of those. And I think that's, you know, if I had one takeaway from your book, it's that we have to, all these systems have to work together. We cannot work with them in isolation either on a micro level, you know, like the cellular level and the enzymatic level, but also on a global level. Well put. That's a great way to summarize what I'm trying to get across, which is we can do better as individuals, as family members, as parents, even as children, we can do better. And it goes all the way up to the top, the leadership of the world, that they also can do a lot better job to make our lives better both physically and mentally. How do you feel about doing just a little rapid fire? It's seven little questions.

Okay. I'm ready. Sure. All right, so this is our rapid fire little breakdown with David Sinclair. What was your mom right about? That you've got to be good to your kids, or they'll come back to buy you later. What was your dad right about? Work isn't as important as you think it is. It's good to spend more time with your family. What's the location for you that promotes your best mental health?

Where I am right now, staring out at the ocean on. I kind of want to answer this one for you, but I'll let you do it. If you had a mantra, what would it be? Live every day like it's your last, but enjoy it like you've got another thousand years. Who are you most competitive with? Oh, that's easy. Myself. And finally, what's been, if you had to pick one moment in your life when you had your strongest moment of best intuition, besides saying yes to being on my podcast. Yeah. Yeah, when I was 26, I woke up in the middle of the night and had a vision as to how to explain why yeast cells get old and age and die. And that was the turning point in my career.

And it turned out to be right and led to where I am today. That's pretty awesome. David, thank you so much. I really, it's really been an honor to have you here. and I'm so grateful at how bold you have been, you know, to be a guy who came here to be a biologist and has really transformed the way we view, you know, aging and science at all. So thank you so much. Oh, well, thanks to have me on. And you're an inspiration to a scientist who's done good. Thank you. Trying. Just a little bit of that time.

You had a lot of emotional reactions to that book, to the idea, to the concept. It makes me really mad. Do you think there's anything in it that you're upset because of the type of death and pain that you've seen in the end? And maybe there's an aspect of like, wait a second, if it didn't have to be like that, what a waste that pain was? You know, I think that, you know, my personal experience has been that, like, life is really hard. You know, my grandfather lived to 94. And he would walk. He walked about eight hours of the day.

for most of his life, meaning he believed you stay young by walking all effing day and having an enema every day. He called it a Spritzke. There's no word for enema in Yiddish. Why do you need it? I don't know that I would have wanted, you know, to see really any of my grandparents, you know, have to live the way they were living. And like, that's why this is so difficult for me. Because many people don't want to experience what they're experiencing. You know, like, has anyone known someone who's killed themselves? I have. You know, you don't just like say like, oh, here's another thousand years to figure it out with the same shitty resources you had and the same lack of help that you had. Like, I don't know if that's the answer. I'm sorry, I have such an

emotional reaction to this. It's like, I had two grandparents who got dementia at the end of their lives completely differently. And a grandfather who worked, my father's father, who worked almost till the day he died, retired, and then two months later died of a massive heart attack. My grandfather died also, like, right after retiring. And if people could have a better quality of life, then... Yeah, but they needed to have been born in a different family. They needed to have a different history. Like, it's just, it doesn't feel that simple.

Like, you, like, you, like, you want to talk epigenetics? Like, generational trauma. and it's not just the Holocaust. It's like for all of history, people have been raised with raping and pillaging. Like, it was standard to not even love the person you were with. You were just matched to whatever dude was old enough to be your grandpa and would get you pregnant.

Like, that was the female existence. I don't want a thousand years of that shit. That's what most of history for women has been like. How can I serve you? How many children can I have? Most of them are going to die anyway. Oh, don't get to. attach to them because they might die, right? And just like make more, cook more, do more.

Oh, you can't even have an education because we don't even believe you deserve that. You also won't be able to vote. Like that's most of what we're talking about. So it's like, sure, yeah, let's all live longer. You tell that to the, tell that to people who are, you know, raising kids on food stamps, who life is beating them down. But we're spending an enormous amount of money on health care playing whack-a-mole medicine trying to solve heart disease, trying to solve cancer, trying to solve all these issues that are arising. Oh, how about we just live forever? I think you should take back the live forever and say, what if we have a much healthier

existence along the way that we are living? 100%. And not have neurodegenerative diseases, not have to go blind, not have to have heart disease, reverse type 2 diabetes, and the amount of money that would be saved in healthcare system, which is anyone who's spent any time in the health care system knows is an absolute disaster. We have to change something in order to redistribute resources and to create more equality and trying to prevent large amounts of disease. It seems like a good place to start.

I mean, it's like when he talks about, like, you should be prepared to meet your your grandchildren, your great-grandchildren, your great-great-grandchildren. I'm like, where are we all going to live? That's what I was thinking. I was like, you know, we're not made to live across oceans and, you know, so it's like, as it is now, families are so fragmented

when someone knows that they're loved, you know, when someone knows that people are praying for them. What it means is that that person knows that they're part of a community so that when they go in for a surgery or, God forbid, or, you know, deal with something, it's like, oh, I have, you know, resources to be able to try and believe,

that like I matter, you know, and like people are wanting me to be okay. But for people who don't have that, like the aging process can be very, very lonely. And like, you know, there's an entire notion, you know, in Western culture in particular, that when you get old, you get sent to a home. Yeah. You know, and it was like when my dad, you know, when my dad got sick, it's like, I was just so grateful that he didn't have to go somewhere, you know, and that we had hospitals, like in the house, but like many people don't even have that option or like, you know, old people are just like sent to live in a home, you know, like when my grandparents lived in a home, I mean, I spent time also just talking to other people who lived there. Nobody visited them, you know?

It's like, I don't know how that changes if we live longer. You know, when we talk to David about, you know, genetics and what gets turned on, like there are diseases in certain genomes that can get turned on. I sure fix all that stuff he has presented science that people can do right now that can impact them and everything you're saying about calorie restriction and eating disorders is very true and very important that we make sure that people who have those tendencies and are struggling with those issues are not taking this as an excuse to starve themselves i cannot demonize eating and to say that you're going to cheat death by restricting your calorie intake. I've read those studies. I've been to graduate school. I know what he's talking about. You don't just apply that to a human. I don't live in a cage. We have to be able to challenge what is normal and we have to be able to think, what if I did something differently? It's not necessarily to say that I will live forever. It may be that I will be more resilient as I live. It may be that

I'll experience less pain, less degeneration of a certain part of my body and that I'll be or I started doing cold therapy. I hate cold therapy. I hate cold exposure. And yes, I started doing it because I had a reduction in inflammation. I had a reduction in pain sensation. I'm going to say something very mean.

Go ahead. I'm sure. And just the simple self-discipline of making myself have to do it was an immense achievement. This is such a bourgeois conversation. To be in the cold, anyone who has water can expose themselves

To say that he has one meal a day, there's some people that's all they can afford. Do you know what happened when COVID hit? And all of the children who got their meals from public school programs couldn't eat. They were stuck in their homes. You know, sometimes you have to take a cold shower because you can't afford hot water. It's like, sorry. No, I really, I respect him very much. I respect him as a scientist very much.

a very thorough biologist, and I also think that, you know, it's very difficult to step out of your science mind and share about your mother and, like, your grandparents. I mean, it's really, it's a very, it is a very, you know, it is, it's not an easy book to read clearly, as you can see what happens when you read it. No, but it's, there's a lot of, I mean, we talk through, we essentially talk through the book, and I was like, okay, now he's going to talk for 10 pages about this gene. Okay, got it. So I do recommend the book. I mean, honestly, what I wish I could show people is, like, the pages that I've dog-eared that are, like, the kind of take-home messages.

And, you know, this is something maybe we can do another episode about, because I think there's a lot here. Suffice it to say, you know, it takes all kinds. And I'm just going to say that. It takes all kinds. It takes David Sinclair. And, yeah, it takes people like me who are weeping about David Sinclair. It's going to take all these kinds of brains and hearts, you know, to put it. it together. Yeah, do you want to talk about anything else or we go bye-bye?

Well, if people have questions about longevity, hit us up at the Bialicbreakdown.com. That's BIA. L-I-A. Breakdown.com and check out the new, new-ish Instagram page at Bialick Breakdown. From the breakdown I'm currently having to the one that we hope you never have. We'll see you next time. It's my Bealick's Breakdown. She's going to break it down for you she's got a neuroscience phd or two one fiction and now she's gonna break down