#136 David Sinclair: Reversing the Aging Process
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The reason I'm talking to you today is to wake people up and realize there is no law that says we have to age. Now, if you force me to give you a number, I'd love to live beyond 100. I wouldn't say no to 120 and I wouldn't say no to 150. Right now, there's a limit because that's what we've seen happens. But the people that live over 100 typically don't take care of themselves. A lot of them smoke and some of them smoke and drink and don't eat good food.

So what happens when you have great genes, which is 20%, plus people who do the optimal lifestyle and take the optimal supplements and take the optimal drugs, there's no reason why 120 needs to be the maximum human lifespan. There's nothing in biology that says that there is a limit. Welcome to the Knowledge Project podcast. I'm your host, Shane Parrish.

The goal of this show is to master the best of what other people have already figured out so you can unlock your potential. To that end, I sit down with people at the top of their game to uncover what they've learned along the way. Every episode is packed with timeless ideas and insights that you can use in life and business.

If you're listening to this, you're missing out. If you'd like special member-only episodes, access before anyone else, transcripts, and other member-only content, you can join us at fs.blog.com. Check out the show notes for a link. Today I'm joined by Dr. David Sinclair, tenured professor of genetics at Harvard Medical School and an expert researcher in the field of longevity.

Dr. Sinclair is also the author of the book Lifespan, Why We Age and Why We Don't Have To, and the host of the Lifespan podcast. I've wanted to talk to Dr. Sinclair because I'm interested in learning about the things that I can do now that set me up to live a long and healthy life.

We go deep on the process of aging, how, what, and when we eat matters, sugar, why stressing our bodies through exercise and saunas is important, the role of attitude, the importance of sleep, the three supplements he takes daily, on whether it's too late to slow the effects of aging, how long we'll live, how long we should live, and more.

We also talk about Lyme disease, and I open up for the first time about my experience with it. If you're interested in living a long and healthy life, this episode is for you. The lawyers want me to remind you that Dr. Sinclair is not a medical doctor, and this episode is not medical advice. Please consult your physician before changing anything. It's time to listen and learn. ♪

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Marcus Aurelius said death smiles at us all. All we can do is smile back. And I feel like you sort of get up in the morning and you look at the god of death and you simply say not today. I do that actually. I do bounce out of bed thinking every day is a miracle to be a functioning living organism. And I know that time is short. We live for a

not even a blink of an eye in geological time. And so I live my life like that. Carpe diem is another motto that I would say to myself many times a day, actually. And working on aging and forestalling

ill health and death certainly does act as a motivating force. Not so much for myself, honestly. I'm not really afraid of dying, but I am aware that every day over 100,000 people die from aging itself. And it's something that I'd like to alleviate. If not extend lifespan by a century, what I would like to do is to at least have people live another 10, 20 years in good health. What is aging, biologically speaking, and why is it a problem?

Well, if I have to tell you why it's a problem, then we have a problem. It's one of the largest costs to our economy globally. It's more sick care than health care. There's a huge amount of suffering for the individual and of families. Anyone who's seen someone die understands that it's often not a pleasant process.

And it can take many years and the final moments are extremely stressful for everybody and often painful. So, you know, that's in itself enough motivation. But, you know, the economic reasons are really important. We just calculated with my colleagues in London who are economists, and they calculated that the U.S. alone, just by slowing down aging by one year and making people productive, more productive for one year,

would save over the next three decades $86 trillion, which we waste now on just keeping people alive in a sick state. And they're not productive, of course. And so if you do it for 10 years, it's $365 trillion. That's a lot of money that can be used for education, additional research, health care, and even combating things like global warming, climate change.

I can't think of a more important thing to be tackling right now as a species on this planet. What happens in our body as we age? Yeah, so there's a growing consensus that what happens is we lose information that we got in the womb. Now, part of it was from genetics, right? We're carrying one copy in every cell of our mother and father's chromosomes. But we're also...

are in fact largely determined by what's called not the genome, which is the DNA, but the epigenome. And the epigenome are the control systems that tell the cell which genes to turn on and off. And there's 20 something thousand genes, but they only use a few thousand to specify how to be a nerve cell versus a skin cell. And this all gets laid down as where embryos and

eventually born. And this epigenomic information that tells cells how to behave, we think breaks down over time. And that results in diseases, tissue dysfunction. So you start to look older, you can't clear toxins, you can't think well, your nerve cells don't work well, you become less able to see at night. Eventually you get diseases that kill you. And that's really the major cause of suffering on this planet. And what we've done as a medical community is

is to look at the end stage of this process, and we call these things diseases, and try to treat them with drugs and basically put in Band-Aids on the problem, forgetting what got us to that point in the first place, which is aging itself, which I have proposed and is increasingly thought to be the case, that it's disruption of that epigenetic control system that tells the cells which genes to turn on and off.

And that's sort of the information loss. And I think one of the analogies you've used before is like a DVD player and a DVD getting scratched for those of us over 40, I guess. Yeah. I didn't realize you're over 40. You look young yourself. So whatever you're doing, keep doing that. Yeah. So the DVD or the CD analogy works well with older people. But anyone who doesn't remember, these were plastic discs with foil that had little pits inside.

that represented zeros and ones, and this is digital information. And that digital information in the cell is DNA. And it's not zeros and ones, it's A, T, C, G chemicals. And they're strung out about six feet long of DNA in every cell. And that's about the same amount of information that you can fit on a DVD. Okay, so our cells are a DVD. But what aging is, I've proposed,

is that it's like scratches that disrupt the ability of the machine, the laser beam, to read the right songs at the right time or the movie. And you get a horrible cacophony of music. And what we've discovered is that there are ways to, well, we discovered one of the main causes of scratches, that's broken chromosomes, which happens all the time in our bodies. Extreme cell damage also does that if we crush nerves.

But we've also figured out and recently published that there's a way, we think, to polish those scratches so that we can play that beautiful music of youth again. Let's talk a little bit about sort of like reducing our biological age. And I think we're all interested to some extent, some people more than others, in living a long time. But we all want that time to be

Full of vitality and productivity and not just living longer for the sake of living longer. And I think that's where the biological age versus your chronological age sort of becomes important.

One of the ways that I've heard you talk about before is fasting. And it's super interesting because fasting isn't new. I mean, it used to be a necessity for us, but now we're starting to learn about why it's helpful. Can you talk a little bit about the benefits of fasting and how it relates to slowing down or even reversing aging? Yeah, well, these systems that tell cells how to read the genes at the right time, this epigenome, there are factors that control that.

And so a little bit of biology here. DNA isn't just floating around the cell. It's actually looped into big loops that tell genes to be switched on. And genes that should be switched off are bundled up tightly. And we call this stuff chromatin. And those loops of genes that are on and bundles of genes that are off are controlled in part by a set of genes called the sirtuins.

And those genes make proteins that cause these loops and bundles, particularly they create these bundles to keep genes switched off. Because you don't want a liver gene or a skin gene coming on in the brain. But that's what happens with aging, we find. And so one way to make sure this process goes slower is to turn on these sirtuin epigenetic regulators, to use a more technical term.

And there are seven of these epigenetic regulators, the things that prevent the scratches. And we can turn them on with gene therapy. In mice, we do this. And if you do it in the brain of a mouse, they'll live longer. Do it in the body, they can live longer. But we can't genetically modify ourselves. So what we've also found is that these genes get turned on by adversity.

adversity or at least perceived adversity, if our body thinks we're going to run out of food or we need to run away from a saber-toothed tiger or we're chasing a mastodon, then our body says, oh, you know, times might be tough. Don't put all our energy and resources into growing bigger muscles. In fact, put some of that energy into surviving, hunkering down and defending the body against

uh toxins against damage and that we know leads to longer life it slows down this clock of epigenetic changes uh which we can measure uh and we also know that um the ways to mimic adversity include skipping meals eating less protein in general being hot and cold and then the big one

is eating the right types of food that we all know are healthy Mediterranean type diet. And there are actually chemicals within those foods of a Mediterranean diet in olive oil and red wine that we found in my lab to activate these sirtuins and probably also slow down the clock, but they certainly improve health. And then the last thing, Shane, that I think is really important is what I'm working on is not about keeping people older at the end of life and alive for longer,

It's the opposite. We're keeping animals and increasingly we're showing with people that you can keep them younger for longer so that when you're 80, you can actually be 60. Is there, there's so many different directions I want to go in here, but is there a point where fasting becomes, I mean, there is a point unhelpful, right? Like if you don't eat, you will die eventually. Yeah.

Is it sort of like you skip one meal is good, you skip two meals is great, you skip six, and you're back to good again? Or is there sort of like some sort of limit that we should think about in terms of maximizing the benefit if we are going to pass? Yeah, well, there's some real key points to hear. One is we're not talking about malnutrition or starvation, that would not be beneficial. And in fact, when, you know, 10,000 years ago or more,

People were not living a long time from fasting because they were not getting enough nutrition. But in our world now, we can have not energy drinks, but drinks that contain enough nutrients. We can make sure that we're not deficient. We can measure things with blood tests and we can make sure that we're not deficient. But the optimal, the second point is that the optimum is different for everybody, in part because we have different tolerances for

not eating, but also because we have different microbiomes, we're different genders, we just are genetically different. And we know from studies in mice that you can take regular lab mice and mix up their, like breed them in a way that you get a little bit of diversity in these lab mice and give them caloric restriction so you don't feed them more than I think it was 40% what they would normally eat.

And some mice breeds strains, we call them, lived a lot longer. Some of them died earlier. But practically, what should you do? Well, it seems to be a rule that if you fast at least 14 hours, you'll have a lot of health benefits, better metabolic stability, lower blood sugar levels, better cholesterol, these kind of things kick in.

A popular one is the 16-8, go for 16 hours. So you skip one meal a day and have a late lunch or an early lunch, depending on which one you're skipping. And that uses the period of sleep as a fasting state. And then what I do is I skip breakfast and often I skip lunch as well. And so I'm getting actually more like 20 hours of fasting on a good day.

I will say that today I had a little bit of avocado for breakfast because I had to get up really early. So I'm not perfect, and I don't think anyone should strive to be perfect, but you do what you can. Now, there are other people that do a week-long fast. Now, that's the other extreme. I wouldn't go further than a week, actually, given what I know. But once you've gone more than three days, there's a special type of recycling of proteins that's very beneficial called autophagy or autophagy.

And that takes about three days. Now, I've never done that myself. I'm pretty wimpy when it comes to these kind of things. I'm a hedonist by nature and very lazy. But I think that if you can go three days or four days, that would be occasionally, of course, not every week, but you could do that every few weeks. And if you do a week-long fast,

You want to do that maybe four times a year. And those are the rough guidelines. If we fast for two meals and then on the third meal, we eat as many calories as we would have eaten during the rest of the day normally, are we still getting benefits of fasting? Yes. Yes, yes, yes. We are. That's the great news.

So take me for example, I have big dinners because I'm making up for the lack of food during the day. And so I'm not losing weight. Once you've hit a set point and you've got your body weight, and during COVID, I dropped from 150 pounds to 132. I'm now steady at that 132, feeling great, eating tons of food that I always wanted, but it's packed into an hour or two of feeding.

Now, how do we know that works? Well, we know from blood tests in humans that it looks like it's beneficial. You get the kind of changes that are seen in younger people, things like I mentioned blood glucose, and then there's hormone levels and stress levels, which I've been measuring in myself for a decade. So I can tell you for me, it works. But the other thing that's important is that from animal studies that have been done over the last 100 years in mice and rats and dogs, it's very clear that it's not

just what you eat, it's when you eat. And there's a very famous study that was done by a colleague of mine, Rafael de Cabo at the NIH in Bethesda. And he made three different types of diets for mice. One that had a lot of protein, the other had carbs, the other had fat. And he thought he would find the optimal diet for the mice

Turns out it didn't make any difference. What mattered was when he gave the food. And if he gave it to them just within this short hour long window every day, they live dramatically longer, 30% longer. That's fascinating. Where does the notion that we should even eat three meals a day come from? I suspect, and I want to research this for my next book, I think it's the food producers that they want

that it become a saying that breakfast is the most important meal of the day. And then you've got the bars, the food, the snacks that we now eat in between meals. For some reason, doctors, nutritionists were either educated or misinformed or both that the body is best when it's never hungry. And we know that is not the case. And just one point on the hunger. I typically am not hungry.

Now, if you start fasting and you've never done it before, you will feel hungry. There's a hormone called ghrelin, which will cause that. Of course, it's not real. Hunger is just mental state. But after three weeks, you find, I found, that the state of hunger goes away. So during the day, I'm not peckish. You know, I might eat some nuts or whatever just to suppress a little bit of twang, but

I'm not starving by any means, and I actually really, really enjoy my dinner as a result. But I tell you this, Shane, and your listeners, because if you try to do what I do tomorrow, you will fail. You need to slowly work up to it and learn the tricks, like drinking water, drinking tea, fill your stomach with hot or cold water and fluids, and that'll help.

I found I used to eat out a lot before COVID because I used to travel a lot and I was always found myself in a restaurant. And I always found that I'd eat more in a restaurant for whatever reason than I would at home. So I've always used this thing where I have two glasses of water before a meal. And that was a way to slow down or sort of at least reduce how much I was eating in the restaurant. Yeah. Well, that's a that's a trick you can use every day. I do it. I'm drinking.

For those that are listening, I'm drinking some water here right now. Actually, it's a supplement drink. But yeah, that's a really good trick. And also, you want to eat your carbs after you have protein because that'll prevent your glucose from shooting up too high. And glucose, I wouldn't say it's poison. We need glucose to survive.

But this typical Western diet of spiking glucose after breakfast, and then it shoots back down and becomes now your hypoglycemic, as it's called. You start to get the jitters, brain fog. Now you eat again. And this cycle throughout the day, which is a typical Western diet, is really not very enjoyable once you realize that when you do what I do, your liver is making glucose throughout the day at a perfect level.

And it doesn't go up and down much. And you can focus and you're not worried about where your next meal is and your brain's really optimal. And that to me, I wish I'd started 20 years ago, eating less often, because you don't just look better, you actually can perform better as well. I like that a lot. And it's not just physical performance. It's also mental performance, right? 100%. You know, I'm not a physical guy, right? I'm sitting and typing mostly and using my brain.

And I'm way, I wouldn't say smarter, but I'm way more focused than I was. I don't get distracted. I don't have memory loss. And I'm also not wasting money and time on meals during the day either.

But yeah, it's fascinating and it's been shown in mice to be true as well. And I think what's also likely is that my brain activity and health will be maintained for a decade or more longer by adopting this kind of diet. So let's talk a little bit about what we eat in terms of reducing aging or sort of reducing that weight.

biological clock? What are the best things to eat? I know it sounds a little bit repetitive, but it is individual, but you can make some generalizations. So first of all, the individual differences are obvious. There's your body type, but also your gender. And I think just as important, your physique. If you are into bodybuilding or you're an athlete professionally, that's very different than someone like me, who's just using their brain and their fingers to make a living.

So there's that consideration. And there are hacks that I'm helping develop that allows you to be in the adversity state, which is what we were describing, eating less, consuming less protein. That's the adversity state that's longevity. But then have periods where you can have an abundance state. And so perhaps I would suggest trying on days that you work out, assuming you're not a professional athlete,

having some extra protein, eat a little bit of fish, for example. But mostly for that adversity state, you want to be focused on plants. Why is that? Because plants have less available amino acids. Your body has to work harder to get them out. But they also have a ratio of amino acids that turns on some of these defenses that I'm talking about. A very important one is called mTOR, little m, capital T-O-R.

And it's there to sense how much protein you're taking in. And if it's always sensing that you're eating protein, it will not

uh turn on the survival pathway that leads to longevity so you'll look good if you're always eating protein because your body is yeah i got plenty of energy let's go for it let's grow but if you never have that state of want that adversity i'm convinced and the data shows it from population studies that a carnivorous diet isn't a longevity producing diet in the in the long run right but in the short run of course

you'll feel better. And a lot of people argue with me saying, I feel great. How could this be wrong? But, you know, remember, life is long. You want to look at ways that will extend your lifespan two, three, four decades from now.

But I think you can have both. I think that it's all about pulsing it, doing adversity, and then occasionally having the abundance as well. And you mentioned a Mediterranean diet earlier. Is there anything that we've learned about what we know about what we eat and like high fat versus low carb versus all of the stuff that to maximize our longevity? Yeah. So the amazing thing about the state of knowledge of humanity right now is that

Over the last few thousand years, humans have figured out to eat less often. There are states of fasting. Most religions do that. But also the types of foods. Mediterranean diet is a good example. There's an Okinawan diet, which is a Japanese island that

has mostly plants and a little bit of fish, but mostly it's not overeating and there's not huge amounts of animal fat and animal products and dairy in a typical long lived population that I just described. So that we've known for a long time. And, you know, it's crazy that we're debating this Mediterranean diet is just known to be healthy and vegetarian and vegan diets are also conducive to longevity. Um,

But the other thing that's amazing about our state of knowledge is that people like me have discovered genes that control aging. Sirtuins are the ones that we work on, this mTOR gene that I mentioned. Those diets are turning on those defenses that we discovered not because we were studying diets, because we were studying yeast cells and worms and fruit flies. But now we understand in this unified theory of aging that by eating these types of foods, you're making the body think that times are tough.

turning on the defenses that for the long run will be conducive to longevity and forestall these diseases that will kill us. And in the short run, you'll actually feel better

And in terms of body composition will actually look better too. Assuming we're eating like, let's say a green pepper or red pepper, is there a difference between organic and inorganic or ones that have undergone stress and ones that haven't undergone stress in terms of how our body processes that? Yeah, for sure. The other reason to be focusing more on plants

is that they make molecules that are very healthy for us. And again, we scientists have figured out that those molecules aren't just being antioxidants. You know, that's the theory of the 1980s. What we've realized is that in addition to being antioxidants, they actually turn on those longevity pathways, the sirtuins. They work on mTOR. There's another one called AMPK, which senses blood sugar and energy.

And by eating plants that, in general, make these molecules, and especially plants that are stressed themselves or have adversity, which heightens the amount of these molecules production, we can ingest them and trick our bodies into thinking that there is adversity, right? We've evolved, I believe, this is my theory with Conrad Howitz, is that we're sensing the plant world and when our food supply might run out, we need to defend our bodies against

the environment, and that leads to longer life. And the theory came from our discovery that resveratrol from red wine and 19 other plant molecules that are produced by plants when they're stressed turn on these sirtuin defenses. And we're trying to figure out how is that possible? Is it just a coincidence? And then we came up with this theory that

we've evolved to sense our food supply. I want to come back to resveratrol later, but just for people listening, don't run out and grab a glass of red wine. I think you'd need like a hundred glasses of red wine to get the amount that you would

You would need. We'll come back to supplements in a second. Are organic plants stressed more than inorganic plants or unorganic? I don't even know what the opposite of organic is. I suppose it's non-organic, but plants are definitely organic. But yeah, they're growing organically, so they're under more stress. They wouldn't have as many

herbicides, well, pesticides on there. They're not grown in perfect conditions. The best ones are locally grown ones that are in a local garden where the environment, the temperatures, there's diseases, there's caterpillars. That's the best kind of environment to get your food from. And if they don't look pretty, that's not a bad thing often. The other thing you should look for is bright colors.

nutritionists have known this for years, that they're very healthy if you eat those bright orange, dark green, red fruits and vegetables. The reason that I think colors are good is that they're indicators of stress. If you stress a fruit or a leaf, you've probably seen it changes color, gets brighter. And those are chemicals that protect the plant, but also are produced in combination with what

these health-promoting molecules are involved in. I wanted to mention a word that may be foreign to your audience, which is xenohormesis. And this is a term that Conrad and I coined. Xeno means across species, and hormesis is this idea that what doesn't kill you makes you live longer. I mention that word because if you can remember it, you'll live that lifestyle. You want to induce hormesis, which is

a state of want, adversity. And you can also get that from other species as well as do it yourself by like doing what we said, don't eat as much, eat plants that don't have as much protein, which is being sensed. And then other things that you can do like temperature changes and

And exercise these all put the body in that state I like the idea of adversity and I want to explore that in different paths including exercise and some other ways that we cause adversity there's two things I want to I want to go into you on food before we move to a new topic one is

Is there a notion to eating things in season? Like I go to the grocery store, apples are there 365 days a year, but they're not ripe on a tree 365 days a year. They have a season, they have a time. Should we be eating with that season?

Or is that a good thing that these plants and fruits are available 24-7, 365 now? Yeah. Well, so it's known that if the plants are in season and otherwise healthy, they're actually, they have the energy to produce these molecules. So yeah, in season, but grown under conditions that are not perfect.

Okay, the off-season apples, the ones that are a little bit flowery, I would avoid those. They don't have the abundance of nutrients and chemicals that we want. But yeah, it's so organic in-season vegetables and fruits is the way to go. And that's what I have turned to in my lifestyle, increasingly so as I get older, and then increasingly regretful that I didn't do it earlier. For those of you who are not watching this on video,

I'm now drinking a cup of hot matcha tea, the green tea, the very concentrated green tea. Those leaves that are grown often in Japan, they come from green tea plants that are put in shade conditions before they're picked. And it's that lack of light that causes it to become bright green, but also produces molecules that are healthy. There's one called, for short, ECGC, which is known to be a xenohormetic molecule to turn on the body's defenses.

And pretty much every morning I start my day with one of these. And it's a great way to start because there's, of course, no sugar in here. It's boosting my body's defenses, but it's also filling up my stomach so I don't feel the need to eat breakfast. When you say boosting defenses, you mean from the antioxidants? No, actually. So ECGC is slightly antioxidant, but it's actually...

It inhibits and turns on the right enzymes that are known to invoke longevity in animals and probably in ourselves as well. It's another one of these, you know, hermetic molecules in the same class as resveratrol, olive oil or components of olive oil. And there's a whole bunch of them. And, you know, we can talk more about these when you want to get to the supplementation. Let's talk about sugar before we get into some other categories.

adversity states. What do we know about sugar and its effect on our biological age? Not that much. So the biological age right now is measured

number of ways. You can do a panel of 40 blood tests. InsideTracker is just one that I use. The other more epigenetic related, so back to the scratches on the CD, you can measure those scratches. It's called the DNA methylation clock or the Horvath clock, named after Stephen Horvath, a scientist at UCLA.

And these are the chemicals that get added or subtracted from the DNA molecule that tell genes to be on or off. And the sirtuins that I work on help control that process. And you can read these with a DNA sequencing machine. And DNA sequences, you know, we're using all the time now in the lab. And by reading those chemicals, where they are and how they've changed over time, for instance, Shane, I could take your blood or a cheek swab.

and tell you biologically how old you are relative to others your age. And so your birthdays don't matter as much for your health as your actual DNA methylation age or your scratches. Now we can measure that, but to your point, we haven't known about the clock long enough to know if glucose or sugar directly impacts that clock. What I can say is that people that eat a Mediterranean diet have a slower ticking clock

and people that exercise and do the kind of things that I'm telling everybody today to do, in general have a lower biological age than those who do all the terrible things. Don't exercise, smoke, become obese. These are ways to greatly accelerate the rate of aging. How would a listener go about testing their biological age? There are some companies that have just started up that measure this from a blood sample.

uh it's fairly expensive it's a few hundred dollars at least my student one of my students at Harvard has developed a technology where we can measure this clock very cheaply for at least 10 times less than that and we're about to release a product in this sometime this year that would be a cheek swab which is far easier than a blood test of course and so just for

a lot less money. And hopefully more often you can look at your biological age and say, well, is my new diet affecting my age? Have I slowed it down? Am I reversing my age, which is increasingly doable? There's a website. If people want to sign up, I hope it's okay. If I've mentioned that people often want to know. Please do. Yeah. Thanks Shane. It's called Tally Health, T-A-L-L-Y health.com. And there's a wait list, but get on that because we're also looking for

people to help us try and figure out through experimentation what happens when you eat certain things or take certain supplements. And so we'll guide you through that. We'll give you your credit score for your body. And then the goal is to use science to slow down and reverse the ticking of everybody's individual clock so that, you know, getting 14, 15 years extra life is not that difficult.

Just by doing the things that I'm talking about today, you'll get an extra 14, 15 years on average. But then I want to help people get 20 years, 30 years beyond what they would have otherwise had. You mentioned exercise. And I know some people love exercise. I'm not one of those people. I sort of do it, but I don't love it. I don't look forward to it. Is there any hope for me? Like, is there a point at which...

I can maximize the advantages of exercise, but not, not anymore like declining utility. Well, I feel for you. I'm the same. I'm lazy as I mentioned. So let's see. So, so what, what's recommended by doctors who know what they're talking about? It's you want to have two types of exercise, at least three, if you can. So what are they? There's

There's yoga, Pilates, that's for joint stretch. That's the basics. Important for longevity. You don't want to break bones if you fall over. The other is weightlifting. You want to exert your muscles, grow muscles, at least maintain your muscles. By the time you're my age, I'm 52 now, I'm losing more than 1% of my muscle mass every year if I don't exercise. So lifting weights, that's important. Then the third type is aerobic.

And the minimum amount to have benefits, pretty substantial benefits, though, would be to lose your breath at least once a week, preferably three times a week for 10 minutes. So that's not a lot. But even that, I'll admit, is hard for people like you and me to do. But it's not as though you have to go running for an hour or cycling for 100 miles. It just a little bit goes a long way. And what's happening when you exercise is

is that again it's turning on these defenses that your body thinks is needed to survive. But you know I'll tell you something more personal and this is not medical advice, it's not science, but I do everything really well except two things: sleep and exercise. Those are my vices. I try to sleep but I work a lot, I travel a lot.

but I know I'd be better if I could sleep seven hours a night. I'm more like five to six. The other thing that I don't do that I prescribe or recommend is exercise. And I rarely lose my breath. I try, I used to have a treadmill pre-COVID and I would do that, but because of the pandemic, I'm not doing a lot of that. So I probably lose my breath maybe two days a week, not as much as I'd like. But my biological age is still getting younger. So I think it's possible to hack it

Some of the molecules that we work on, resveratrol, there's one called NMN, which we can talk about later, but it's an NAD boosting molecule that also turns on sirtuins. I've been taking that. And so my health has never been better. You could argue maybe it would be even better if I exercised more, but I'm pretty happy with my biochemistry. My blood biochemistry is equivalent to a 20-year-old's. I'm 52.

So I think there is hope for us. That's a long answer to your question. But wait, isn't sleep super important to longevity? Like as we age, okay, so here's some notions that I bring to this, right? Like my baggage with sleep is like, as we age, we tend to sleep less. And everything that I know about sleep tends to tell me that sleep is super important for mental functioning, for age, aging well, for aging.

all of these like health benefits associated with sleep. And you're telling me you get four or five hours and you're 52 and you have a 20 year old biological clock. So maybe sleep isn't that important? Maybe, maybe I'm, I might be 15 years old if I could get more sleep, but, uh, we'll never know. But I, I, what I know is that those are two and

genes that I talk about all the time and I've been studying for 30 years, they control the clock and then the disrupted clock affects them because it's a big cycle. And

If you get that out of whack in an animal, if you don't let them sleep, they will age prematurely. If you stop a rat from sleeping for just two weeks, it will develop diabetes. It's really important. So I don't think there's any argument that sleep is important, but can you hack your way around it? Maybe that's what I'm showing. But I don't want to give the impression that I think that that's the best way to live life. I mean, I got up at 5.30 this morning. I went to sleep probably at 1 o'clock.

um that's not a good way to live i i am tired um i i do fine i've got caffeine i've got my nad boosters which do help me get through the day in the morning but ideally i would want more sleep i think that i better memory and focus if i did that there are two hacks that i'm doing that allow me to get away with less sleep now i've included meditation at night into my daily life most days

And that's been very helpful. And the second is that I have a bed that reduces my body temperature in the middle of the night and I get deeper sleep, which also seems to help. Are you using an eight sleep? I am. Yeah. What's your setting profile on that? I use one too. What's your, what's your, do you, do you do warm, cold, warm, or are you like cool, cool?

cold, warm? Like, how do you set that up? Depends on the season. I'm in winter now in Boston, which is my, my apartment's very cold. But so these days, I started out a bit warmer than usual. But what I normally do would say, I get into a coolish bed. And then the next stage is drop me down lower and lower. And then half an hour before waking up, it'll shoot up to

as warm as I can handle it. But yeah, I like to drop the temperature down and I sleep better that way. So coming into this conversation, one of the notions that I had is one of the reasons that we tend to age or accelerate aging as we get older is that we tend to sleep less.

And I guess that's not the case, right? Because I always thought, oh, like, you know, I see this with my parents right now, right? Like they're sleeping less than they used to. And I just assumed that that was part of aging, but also what accelerated our aging. Yeah, I think you're right. And that's the problem. Once you start getting less sleep, you will age and your age will give you less sleep. And that's why it's important to maintain that sleep health.

But NMN, which is this NAD boosting molecule that I mentioned earlier, that is part of the sleep-wake cycle. And one of the hacks that I think is really beneficial is that by taking NMN in the morning, I'm simulating or stimulating the morning response. And I get the alertness and the energy that I would have had if I'd had more sleep. And I can reset jet lag.

You know, I'm a scientist, so people might say, David, you can't mention anecdotes, but I'm going to do it anyway. I haven't had jet lag for a decade because I've been able to modulate my own body clock by using these chemicals, which, as I mentioned, are activating sirtuins and controlling the clock. Now, most people don't know that, but I think if you have paid attention to the kind of things that I'm saying,

out there, you would know that it is possible to hack the clock. I want to go back to the theory of adversity before we come to supplements and sort of like some of the stuff that you do. And with adversity, there's other ways that we can introduce stress to our bodies like hot tubs or saunas. What do we know about saunas and hot tubs? Like there seems to be a strong correlation, at least with saunas, to longevity. Why is that?

Well, so I'll admit when I started writing my book, which was a number of years ago, the editor said, oh, you should talk about saunas and hot tubs. And I said, this is a serious book. Come on. I'm not going to put that.

fashion in there. But I was wrong, actually. There's now a lot of evidence that being in a sauna is good for heart health at a minimum. There's a lot of studies of thousands of mostly men in Finland that do sauna bathing, as they call it. And they are protected dramatically, like they are exercising. But how does that work? Well,

There's lots of theories. It's hard to prove. But one theory is that we have what are called heat shock proteins in our body that get turned on when the body's too warm. And we know actually if you turn on heat shock proteins in animals, they live longer. And they do that because they help fold proteins correctly. And misfolded proteins and the recycling of proteins is very, very important. It's one of the reasons that I eat a plant-based diet mainly is to turn over that protein to

cycle. But yeah, so that's one. Cold is different. We think it's working through a process that is called browning of fat. We have white fat on our back that turns beige or brown by being cold. And then that revs up our metabolism. And this brown fat also seems to secrete little signals that make the rest of the body healthy.

but it's still early days we only discovered we scientists only discovered that brown fat exists in humans about a decade ago so we're really not sure how this works but i can tell you from having talked to a lot of people that do saunas sauna bathing uh cold tubs and myself included that it does have benefits on blood by chemistry and even if it doesn't you feel great um

And, you know, these kind of things, if they make you feel great, you know, why not do those with the potential to extend lifespan as well? I feel like we've been doing some form of like hot therapy for thousands of years through baths and saunas. And, you know, we're quick to dismiss this stuff. But I also feel like there's a reason that it sticks around, even if we can't, even if we don't understand that reason at this point.

that we still use it. I use a sauna like two or three times a week and it, it's super helpful for not only my mental health, um, but my sleep. And I feel like it has a huge impact on my physical health, but feelings aren't scientific. Right. So, right. Right. But, but you know, the, the, I would say there's enough data to say, yeah, you're probably protecting yourself at a minimum against cardiovascular disease by doing that. Um, but I also find that, that my

my lungs benefit from breathing in that really hot air in the sauna. Yeah. And in my case, I walk out and it's like minus 30 Celsius. So I get the hot and the cold right away. So I'm trying to live forever here. And if you don't, it'll feel that way. But yeah, it's all about stressing the body. And sometimes it's the differential that counts.

There's a therapy called hyperbaric oxygen therapy where you go into high pressure and breathe in oxygen.

And then they cycle it. Often they cycle it, not always, where you go high pressure and then low and high. And what I think is going on is that it's not the high pressure that's important. It's the decrease that you're becoming pseudo hypoxic. Your body thinks it's running out of oxygen when it's just coming down from a high level. And my lab has shown in mice that pseudo hypoxia is a real thing.

and is probably mimicking exercise. And the kind of benefits that people are reporting

are similar to exercise, except you're lying down. I've done it a few times. It's really quite enjoyable. You'd get to watch it. You know, you'd appreciate this. I watch Schitt's Creek on, well, I mean, one of these tubes. And, you know, I'm getting seemingly a workout just by lying down. So physical stress is good. What about mental stress? Does mental stress have a benefit? Or, you know, I tend to think it would only be a drawback, like this low level of persistent mental stress.

stress would be bad for you, but maybe if it's intensity and it comes in intensity and then dies to nothing and then comes again, it would be good for you. How do we think about the relationship between stress, mental stress in this case, and longevity? It's important not to mix up the two uses of the same word. So stress that I'm talking about, hormesis, is biological stress, making your body and your cells think that there's adversity.

Psychological stress is just a different beast. It shouldn't even be called the same word. But let's focus on that. Now, we know that a little bit of excitement and thrill is very beneficial. But you can have chronic stress, depression, just the kind of stress that leads to cortisol surging through your body. This is not healthy at all and would reduce lifespan. We know from animal studies that those that are under

social stress will be unhealthy and die sooner. So if you are experiencing that, try to figure out how to reduce your psychological stress. Meditate, breathing exercises,

Just try to avoid worrying too much. This is really important. And I can speak again from experience. I was a very agitated, anxious person in my teens and 20s. By my 30s, I went to Harvard and I thought, if I continue worrying like I have been, I am going to die young. And that's not going to be a good look for someone who works on aging. So I've learned to not worry so much.

I focus on what I can do in the day. I focus on the fact that I'm never probably ever going to run out of food because I live in a wealthy country. I'm not going to run out of shelter. I'm going to have friends and family. And that's all I need to exist. So what's the worst that can happen? Still not that bad. And that's a good way to live life, I think.

Yeah, I think it was Warren Buffett who at one point said something along the lines of the key to his age was the fact that he has no stress in his life. Yeah, when you look at centenarians, the people that live over 100, they have that in common. They have a good sense of humor. They don't worry too much in their lives on average. And they also have good partners. It's been shown by studying hundreds of people over their lifetimes that

that one of the most important, if not the most important factor, is to have a reliable partner. A pet can substitute for that if you don't have one of those at the time. But yeah, you want companionship. That really does reduce your stress levels and leads to longevity. It's been proven.

Does attitude affect our biological age? Like would a positive outlook help you live longer than a pessimistic one? It does. It does. Well, we don't know cause and effect. We're looking at associations, but people who live a long time tend to have a sense of purpose, are driven by a mission. And so that is great advice is to work towards a goal. And, you know, clearly you and I are like that. And I think that also helps people.

Focus the mind, reduce stress. If you're actually working towards something bigger than yourself, you'll have that mental state and you won't be so focused in on yourself and anxious. I don't want to go too deep on supplements. I think you talk at length for over an hour in Lifespan, which is your podcast on supplements, the third episode, I think.

I do want to talk about three in particular that seem to keep coming up across a lot of people I know who are super focused on health. You bring up NMN, resveratrol, and athletic greens, and you take those every day. Talk to me about those three and why you take them and what they do to your body in the context of slowing or reversing aging. Right. So let's take them one by one. Resveratrol is a small, what's called a polyphenol.

It's produced by many plants to survive. It's produced by grapes and it's concentrated in red wine. It should be a white powder, it shouldn't be brown. If you buy it and it's brown, throw it away. I take a gram of it every morning.

with rare exceptions when I'm traveling and I forget it. But I mix it with a little bit of yogurt because it, just a little bit, like a couple of teaspoons. Or today I had a bit of avocado because resveratrol is insoluble in water and often people take it and it doesn't get absorbed. So do that. Why does it work? Well, we have shown in many animal studies and people have now shown in human studies that it's activating one of the main sirtuin compounds

pathways called SIRT1. And it does that like an accelerator pedal. The chemical resveratrol will bind to the enzyme and make it work faster. Now, that's the accelerator pedal for SIRT1. The gas or the petrol is NAD. NAD is a molecule that we need for life. Without it, we're dead in 30 seconds. And NAD isn't something that you can, well, you can swallow it, but

The best bang for the buck is to eat molecules that the body uses to make this NAD molecule. And the one that I choose to take is called NMN, short for nicotinamide mononucleotide. But think of it as M&Ms, but just flip the letters around. Don't eat M&Ms. You won't live longer. You can eat M&Ms, but if you want to live longer, don't do that. But the NMN is important because it's the immediate precursor

to make NAD and the body makes NAD very rapidly. And I know from clinical trials that I've been involved with that taking a gram of NMN, which I do every day, raises NAD levels in whole blood, in the cells in the blood, probably in the rest of my body as well. It's hard to test that without a tissue sample. I'm not going to give up my brain anytime soon. But

the doubling of that NAD is important because as we get older, we make less of this chemical. We have about half the levels of NAD in our skin, for example, as I have half the levels if I didn't supplement that I would have made when I was 20. And so I boost those levels back up to being youthful. And then the idea is that the sirtuin defenses are activated and that's enhanced by the diet that I have as well as a little bit of exercise. Now,

The third one you mentioned is athletic greens. Because I'm on a vegetarian/vegan diet, I describe myself as a newbie struggling vegan, I need nutrients. And so athletic greens is full of vitamins and plant-based whole foods that ensures that I don't lack those nutrients. Because if you're just eating a vegan diet, and I've also given up dairy, you want to make sure that there's adequate nutrition. So

I'm on one meal a day, basically, OMAD. But I want to add another couple of letters, which is A-N, OMAD, A-N. I just made that up, by the way, Shane, so trademark that. OMADin, let's call it. Adequate nutrition, put that on the end. And that's what Athletic Greens does for me. I do take one other drug called metformin, which is a type 2 diabetes drug that has been shown to associate with longer life and less diseases in old age.

by looking at type 2 diabetics. And there's a stunning fact that type 2 diabetics that would normally have a short lifespan, when they take metformin, typically at two grams a day, I'm on one gram a day, by the way, they actually have less diseases and live longer than people that don't have type 2 diabetes.

Why did you give up dairy? You mentioned that you stopped dairy. What caused you to do that? And then did that have any impact? Because I know you monitor your body quite a bit. Did that have any impact on you? Seemingly it did. Yeah. And so I change one or two things at a time and have a look how it goes. And I'm an experimenter. I love dairy. I was eating a lot of cheese and red wine. My diet two or three days a week was a cheese board and a couple of glasses of red wine, maybe more. And

She was looking at what I eat, and she actually said, that's not very healthy. And so I've adopted her lifestyle, which is not so much meat, cheese, dairy. And I've looked at my blood biochemistry, and I'm actually now younger and healthier than I've ever been since I've been measuring it over a decade. Now it's more like 14 years. And I can plot various parameters, testosterone, glucose,

The list goes on inflammation, blood type, blood cell composition. And for most of those markers, I'm better than a 20 year old for for health. And and I think a lot of that's due to my new diet that I've adopted because I can just see things getting better and better over time. I interviewed Alan Campbell, who is the former personal chef for Tom Brady and Giselle Bunchen.

And we talked at length and in sort of about diet and eating for peak mental and physical performance. And it's interesting to me that you mentioned cutting out dairy and seeing this go, because the three things that he mentioned carry the most bang for the buck for, for cutting out were gluten, dairy, and sugar in terms of your sleep, your physical performance, your mental performance. Do you have any thoughts on that? Yeah, I do. I really do. Um,

So I'm a lazy guy. I like meat, right? So I'm an average person. And so I've done this over time. I'm not great at it. And I just mentioned that because sometimes people say, I can never give up alcohol. I could never give up meat. It's not true. And so at least I found it not to be true.

First thing I cut out was a lot of carbohydrates. I used to eat bread every day. I would just put, if I ate something, it would be on toast. Okay. That's my life. I cut that out and I found immediate improvements in my biochemistry levels, particularly my glucose levels.

The next thing I cut out was meat. I worked towards a Mediterranean diet, had fish, and eventually now I'm no meat. And that improved my numbers even better. Cholesterol, what do you call it, triglycerides all came down. And I have a familial history, genetics of heart disease. I have what's called LP little a.

high levels. LP little a is the worst. About 30% of us have this and we're destined if we don't do something to have a short lifespan. That was very important was the cutting out meat. And it's not just the protein. It's also the fat that comes along with the steak and whatever that I was eating. And then the third change was the dairy. I did that just to see what would happen. I figured it wouldn't matter. I'm not allergic to dairy. I'm not lactose intolerant.

But it did have an effect. It made things even better. And what I think is going on, Shane, is that I was eating a large amount of protein, not just fat, but eggs and all that stuff. And now that I have less protein, I think that mTOR pathway that's really important for longevity

in animals and probably people is really kicking in in a way that had never done so before. That's really interesting. And the only other thing I want to mention about Alan Campbell and just out of just so people don't get the wrong idea, he's also super plant forward with a little bit of fish. So it's mostly plant based diet. And it's just interesting how you you've both sort of like

come into the same sphere, I guess, if you will, from very different approaches in terms of that. And I always find that stuff interesting because it makes me think that there must be something there. Well, I don't like plants. I mean, I'm now learning how to enjoy plants, but for me, they were a side dish. But here's the thing. There's a lot of debate, especially on social media, about meat versus plants. I would love meat to be lifespan extending. That would be heaven. But it's not. You just look at those plants

populations and people that live a long time, they are generally smaller women who don't eat much, who eat vegetarian. I mean, that's the fact. We can debate it all day, but there are these scientific facts that we have to pay attention to.

Is it ever too late or too soon to sort of like start to slow the effects of aging? If not, like how do you stage interventions at different points in your life? Yeah. So I would say don't start too early on certainly supplementation. We don't want teenagers that are malnourished and eat too little. But I would say, speaking of myself, because I'm not a professional nutritionist, but I do know the science.

I would, if it was me, start doing the meal skipping in my 20s, but make sure I've got enough calories coming in. I'd start the supplements in my late 20s. Before that, you've got a lot of NAD already. Your body's already defending itself when you're young. It's your late 20s, 30s, things start to kick in. But what about your question, which is more important, which is when is it too late for people? I've never seen it too late. There are animal studies you can, I could point to that show that you can have

affect this mTOR pathway with a drug called rapamycin that extends their lifespan, even if they're the equivalent of 70 years old. And there's a point where you're so frail and so sick, you're probably on death's door, that it's unlikely that you should start exercising and fasting probably. Though that's really at the final stages. If you're still, let's say, a relatively healthy 70, 80-year-old,

My father is a good example. These changes to your lifestyle can have rapid benefits, but do it in consultation with a doctor because you might not benefit from fasting if you need body weight. If you have other existing conditions, it's important to take those into consideration as well. So talk to me a little bit more about your father. Is he eating mostly a plant based diet too? Yeah.

Yeah, so he and I are very similar. People think I'm experimenting on my dad, but I'm not. He's a scientist. He reads the science. And we've come up with this protocol, which is the very low glucose. We don't eat a lot of sugar. We try to avoid desserts. Low carb. Don't eat a lot of meat. He would eat meat very occasionally, but mostly it's plants. He doesn't eat much during the day. He mainly eats dinner and he's lean now.

And what else? He does more exercise than I do. So he's better at that. He does aerobics. He goes a couple of times a week to the gym and does rowing and weightlifting. What else is it? He takes supplements. So he's on resveratrol, NMN, metformin, and that's his cocktail. He doesn't take athletic greens just yet. But he's a super healthy 82-year-old. He was not on that path. In his 50s, my age, he was overweight. He had high cholesterol, looking at dying in his 70s.

In his mid-70s, he went on this protocol and is now an 82-year-old that's fitter than most people that age. He has no diseases, perfect mental health. His eyesight hasn't changed in all that time. And so, yeah, I mean, we're looking forward to this experiment being a successful one. But if nothing else, he's a beacon of hope that you can start late and have big effects.

You mentioned teenagers. Is there a link between when we start puberty? To me, when we think of puberty, it sounds like rapid aging almost, like a concentrated dose of aging. Is there a link between when we start, how long we live, and is that true that puberty is sort of like this rapid dose of aging? Well, I'm going to speak as a scientist with an opinion.

And that opinion is based on all the science that I've read. And I read a lot of papers. Before I get out of bed, I'm reading science papers. Here's what I believe. Now, I don't want parents to get upset with me. I certainly don't want people to worry. But here's what I think will turn out to be the case. The biological clock, the scratches on the CD that we talked about earlier, they start at conception. The egg and the sperm come together.

even an embryo, even a fetus and a young baby, they're aging. We can measure this on this clock. And certainly teenagers are aging. Now we know that obesity and lack of exercise, lack of nutrition, lack of plants is unhealthy. And I would not be surprised if the teenagers are

by the time they hit their 20s, on average are older biologically than they were 20, 30 years ago when I grew up. Because we were moving, we were generally not so overweight, we were not eating as much sugar, and that's probably accelerating our kids' aging rate. Meaning that 20, 30 years from now, 40 years from now, that is still going to echo in their health because the clock is

Unless you do something radical, it doesn't go backwards. You track a lot of your data, right? You have an aura ring on, I think. You use an age sleep. You're testing your biological age. Are we starting to think of biological problems almost like engineering problems where we optimize for specific...

data points in the hope that those data points are correct? Well, absolutely. You know, I was at the forefront. I was kind of this biohacking guy, scientist interested, and I was out on a limb as one of maybe 50 people in the world that do what I did. Now there's millions of people around the world that monitor themselves with rims, with beds, with, you know, with watches. There's plenty of fitness trackers you'd be aware of. They are all part of this global movement

to not fly blind with our health. We can track things. We can see what works, what doesn't. And it was crazy that for up until recently, we would be driving the equivalent of driving a car without a dashboard. Who would do that? You might have a check engine light. You could overheat. Same with our bodies. And going to the doctor once a year for an annual checkup

Now that we can monitor ourselves every hour, soon every second, eventually every thousandth of a second, that world that we're entering makes this old world of going to the doctor once a year seem medieval. And it is. What can happen in a year? You could get cancer. You could have heart disease. You could have a heart attack. Now we have the devices. Some of us use them. Increasingly, eventually, everyone will have them.

We'll know ahead of time if we have cancer, if we have heart disease, if we're going to have a heart attack next week and stave off those things and prevent them from happening. And that is a revolution separate from what I'm working on that will extend lifespan, I believe, by another decade.

It's super interesting to me because we have all of the tools available to us now. We're not using them where I could walk into my doctor's office and I could tell them what I'm feeling or the symptoms that I'm experiencing, but then they could pull up on their iPad or whatever, like all of my biomarkers to see and to gather more data. But we don't, we choose not to use that at this point or we're not ready for it. I mean, privacy concerns aside.

But how do you think about that? Like, we will get to this point where I have like a device in me. I'm sure during our lifetime that I'm showing up at a hospital and instead of filling out paperwork or answering questions, they're just looking at it and they're being like, OK, now we have the data to back up some of these decisions. One hundred percent. There's no question you can take that to the bank, that that's the world that's coming. And I wrote about it a few years ago. And COVID-19 has accelerated that.

I was predicting telemedicine and wellness at home and this whole revolution. I thought that would be 10 years away, and it's here now. So why isn't it so common? Well, partly it's education, and podcasts like this are helpful, but it's also that it's expensive. So we tend to forget that these watches and rings are hundreds of dollars. These tests, these blood tests are also hundreds of dollars.

And our doctors are reticent to be doing all these tests because the health care systems want to save money ultimately, right? Forgetting that ultimately they will save money by keeping people alive and healthier for longer. What's fascinating is that I have this collection of data that I can call up on my phone and it's all graphed by this inside tracker group that you can do others.

And my doctor, I thought he would say, oh, I don't want to trust that data. I only trust the data that I gather on you. But the opposite was true. I actually, I was Zooming with him because we don't tend to go to the doctor as much anymore. And I called up my data on the screen and he loved it. He was into it. He said, oh, this is so great. I wish I had this on every one of my patients.

But yeah, you're right that they the doctors generally don't do that because it's expensive. But we can now do that and then show our doctors and they're grateful. Well, it's so interesting because it's expensive in the moment, but it's super preventative. If we go with the assumption that most medical care costs are at the end of life or from chronic diseases that we might be able to avoid.

then these costs tend to be upfront and they're massively preventative. So they actually would save healthcare systems lots of money in the long run. But we never look at that because we like to treat things. And so like as a computer scientist, I look at this and I'm like, not only can we prevent problems before they happen, but now we can start to get this amazing quantity of data where I can be like, you're showing up with this thing and you feel this way. What we know from...

20 million other people who've shown up with this thing in this way that it's not what you think and it's something different. And then we can save a lot of money and time there as well. For sure. And those technologies exist. I've been wearing what's called a bio button. I have no affiliation. So if you want to look them up, they're called bio IntelliSense.

And this is an FDA approved device that doctors can send home with their patients after surgery to monitor their heart, as well as their movement, their vibration, their temperature. And that data that comes in is actually very informative beyond the heart. They can tell if you've got a flu versus a common cold versus depression, COVID-19. And that's going to, the world will be, you have something stuck on or under your skin that will tell you,

a nurse or a doctor or some sort of AI system that something is wrong and it needs fixing well before you would ever have a problem noticeable by yourself or a doctor.

A lot of money seems to be going into life extension recently. I'm thinking of Altos Labs with Jeff Bezos and some others committed about $3 billion, which is the biggest seed investment I've ever seen in my life. And they hired some of the world's top scientists. It seems like it's set up to commercialize, I can't even say this, the Yamakata factors.

Yamanaka.

at least in the mice. How do you think about that? And is that also the future so that we control sort of like part of our aging and then what we don't control, we can use drugs to reverse or slow down? We were working on this for a while based on the idea that we could find genes that would polish the scratches on the DVD. And we came across a set of three genes called O, S, and K for short, which are three of the

six or so Yamanaka factors. And about a year ago, we published that we could reverse the age of an animal and we restored eyesight to a blind old mouse and cured glaucoma in that animal.

And we are now working towards human clinical trials in Canada. We have a non-human primate study for safety to see how that goes. And within the next 18 months, if all goes well, we will be reversing aging in a human, if all goes well. So that discovery in part, you know, there are a few other colleagues that are in this, but not a lot, led to a huge interest in this epigenetic information theory of aging that we started off talking about.

And the idea is that we can truly reset the age of the body and diseases of aging like Alzheimer's and heart disease and even cancer will go away if we become young again. My company is called Life Biosciences. It's here in Boston. Altos has come along three years later and they're working on this too. But the goal is a great one. I wish them all the best of luck. I hope that they are hugely successful because it could be

transformational for our species on the planet the ability to finally control the rate at which we age not just in the forwards direction but in reverse as well. I want to switch gears a little bit and talk about Lyme disease. Your daughter had Lyme disease. I had Lyme disease in the summer to the point where I couldn't even get out of bed basically and

I had full on Bell's palsy. I like couldn't open my jaw. I couldn't stand still for more than 15 seconds without being in massive amounts of pain. And, um, to, to going to the medical system just briefly, um,

we're about preventative care. So you show up and it's like, oh, you have Bell's palsy. It's not a heart attack here. Take some pregnancy and like go home. And it's like, well, no, I'm a healthy, you know, 40 something year old male. What's causing this? Like, why aren't we going deeper to figure this out? And I'm curious as to what research you did and what you learned about Lyme during the process that most people don't know. Yeah. Well,

Natalie, my middle child, contracted Lyme, I think it was about seven years ago now. And I was exposed to how the medical system works when you have an infection. First of all, it was very hard to diagnose. She had headaches. Who knows what's causing that, right? And I Googled it, I searched it, and I said, it's probably Lyme disease. We took her to the emergency room

And they said, well, it might be this, it might be that. Could be leukemia, whatever. But we'll do a Lyme test. I think I had to insist, but they did a Lyme test. But the problem with the system was that it took three days to get a result that was ambiguous because it's using 1980s molecular biology technology. It's primitive. It's called a Western blot, which we don't even use anymore much. And then...

Because it was ambiguous, the insurance company said, no, we have to have a definitive result before we start treating your daughter with antibiotics. Meanwhile, Natalie is losing her eyesight. You know, like you've said, you can't focus. And she got to the point where I've now been told that she had a chance of dying that was pretty high, 40, 50 percent. At that point, it was in her brain and we were not treating her because the test wasn't definitive.

So that was disturbing. And I also told the doctors, give me a sample of her DNA or spinal fluid. And I've got my lab across the street. I'll go sequence the DNA and I'll find this organism if it's there. And they refused to give me a sample. So, you know, I'm traumatized at this point as a parent.

And when you're traumatized, you'd like to do something about it. And so I started a company that was a spin out of AI that we were doing in my lab. We built our own little mini supercomputer out of GPU, you know, graphic processing units. And we were able to figure out how to find any organism in the blood of a human being. And this company now,

has a product that is being used, for example, by liver transplant patients that are immunocompromised because of the drugs. And we can track the infections that they have, like viruses that come out of their liver and rest of the body. So that's now a reality. It's not mainstream, but eventually it will be.

And when that's possible, you know, you go to a shop, a pharmacy, or you go to your doctor or at home, you do an immediate test. You don't know what's causing the problem. It'll say, oh, we've detected Lyme disease. And by the way, three months ago, you had the rhinovirus, whatever. You know, you can see all that stuff now. And that's going to be a world change.

that's almost here, but when it arrives mainstream, the idea of waiting four, five, six days for a result for something that could kill you, I mean, that again is medieval science and medicine. On the same way, I mean, I had to advocate for a test and it was only actually a friend who gave me a test. My family physician wouldn't give me a Lyme disease test despite all the symptoms that I had. Did your daughter end up taking doxycycline?

Right. It was so severe. She had to have an IV treatment for many weeks. I think it was at least three weeks that were, it was delivered at home by her mom to get rid of it. How did you treat yours? Doxycycline. Yeah. So I just did a cycle of that. I mean, it seemed to instantly, not instantly, but over a period of maybe two weeks, like it went back to normal.

you know, gradually, like I had facial paralysis on half my face and, you know, so it started with, uh, I could stand again, I could open my jaw a little bit more. The last thing to come back was sort of the facial paralysis. And it was scary. I mean, uh, it was really, and it was scary that you had to be an advocate of your own health too, in a system, um, which, um,

you don't know how to navigate, which I also thought, you know, as a parent, you feel as somebody who shows up at a merge with like a face that doesn't work, you also feel it in a different way. Is there any lifespan effect of Lyme disease after treatment? No one knows. Doxycycline in mice, my recollection, I have to check on this. People who are listening can search for this in pubmed.org is lifespan extending. So maybe, yeah,

It's a short course that you took, but maybe there's some upsides. But the problem with Lyme is, particularly if you don't get it early, it can become chronic. It's

lives in your joints, comes out, causes a lot of joint pain. That would be not a state that would be conducive to longevity. Any increase in chronic inflammation is anti-longevity. I like the notion, you mentioned yoga earlier. I'm just circling back to that now. But like you sort of mentioned, well, there's exercise in terms of like lifting weights and running and exerting yourself that way. But there's also preparing today to live a much longer life that might be well into your 100s.

And part of that preparation is you need to stretch and have joint flexibility. And because it doesn't like hip surgery correlate to death, like you break your hip and you basically like there's a strong correlation to people who do that. And then their lifespan is is almost over at that point. It is. Yeah. The chances of dying after you break your hip as an older person is

is about as bad as late stage cancer. And every 19 seconds in the US, at least someone breaks their hip. So it's a massively untalked about problem. A colleague of mine at Harvard made, I guess, unnecessary light of it. But his motto is, the secret to living longer is hanging on to the handrail. And his point's well taken, really, that it's pretty easy to prevent

deaths sometimes. My grandmother, who I wrote about in my book, was really influential in my life, died that way. She tripped on a little bump in her rug, broke up her femur, went to surgery, not enough oxygen in the brain, and then the next five years, she was basically a vegetable, and then died, you know, not a very pleasant way. So

Yeah, it's avoidable, right? If you maintain your hip strength, if you can, muscles, flexibility, you also want to make sure your household doesn't have ripples in the carpet and don't walk on stairs, don't climb ladders, that kind of thing can save lives, you know, and it's not that difficult. And Shane, this is the point I want to make is 80% of our longevity is

and our health in the future is in our own hands. Only 20% is genetic, which we cannot yet do much about. And some of these changes are very simple. Skip breakfast, have tea instead, work out, maintain your muscle strength, do yoga, flex a little bit, touch your toes in the shower if you can. These can add years, if not decades, to your life just by changing things in a small way. You don't need high tech to make a big difference.

Yeah, it's interesting. We always look for that one thing, right, that causes somebody that decision, the drama, the movie moment that, you know, causes somebody to be successful or get results or live longer. And what we, you know, what we miss is the magic that happens on a daily basis. That's this slow, incremental progress that is too fast.

Too little to notice in the moment, but by the time you notice it, it's so great that you're looking for that one magical moment, that one factor that caused it. Yeah, it is a lot of work, I'll admit. It's been daily since my 30s, but it's been worth it. It was an experiment, I should say, but I didn't know if it was going to work. So far, so good, right? I'm 52. I'm not dead yet. But it's every day making the right decisions or better decisions about what to eat.

of course what not to eat, going to the gym or your home gym when you don't really feel like doing it, that's really hard. But these are the decisions every day that need to be made to reap the decades of benefits later in life. And there is no instant cure yet. We're working on it, reset the age with a pill, gene therapy, we're working on that, but that's not there yet. And the other thing that really is important to know is that there are additive benefits

If you eat, exercise, do hot and cold therapy, mental state, if you do all of that plus the supplements, they're additive. It's not that take a supplement and you don't need to do any of the others. In the animal studies in my lab, when we gave NMN, this molecule that I take every day, to a mouse that was sedentary, didn't have a wheel, didn't run, it could run further, okay? And we actually have human data that's looking really promising in that direction as well.

But if we exercise the mice and gave them the NMN, then they could run double that again. And so if you really want to optimize, you've got to do more than just take a pill.

And it's about consistency, right? Most of us try it for a couple of weeks and then we're like, I haven't seen the results. And then we quit. And it's sort of like the equivalent of Sisyphus, like rolling that boulder up a mountain, getting halfway there. And then, you know, just like putting your hands up in the air, watching it roll down back to the bottom. You have to be consistent over a long period of time. And to that point, like growing old seems like a distant event in the future. I mean, it happens slowly and then all at once.

We don't seem to think about it until we're really late in the game or we have a loved one or somebody goes through something. Why is that? And is there anything that you've seen effective at bringing that forward for people? Well, this is what my mission is. The reason I'm talking to you today is to wake people up and realize that you shouldn't just wait till...

something traumatic happens in your life, whether you get sick or your parents or your grandparents. And it's important to realize now that you can do things for those people in your lives, your life and yourself. Typically, we wait until it's too late for those people. My parents, my mother is a good example. My mother died young from lung cancer. She was a smoker who didn't take care of her body at all.

And I watched her live the last 20 years of her life in a really painful state. She had one of her lungs taken out through her ribs. That's not what you want for your mother. I wish that I had the knowledge that I have today that I'm applying with my father to her life. And she might even be around today if we had done that. That's the hope, right? But you have to want to make the changes too. I think that's the key point. A lot of people don't, right? They want to

For whatever reason, they don't want to act on it. So to sum up, maybe like and get a little more philosophical here a little bit, like our average lifespan right now, I think is about 80. If we do the right things in our life, like we eat healthy food and not too much of it, we get enough sleep and we stress our bodies a bit with exercise or saunas and we don't get too much mental stress. We add, I think, about another 10 to 15 years to our lifespan. That's right.

Yeah, 14 is the number that was in that Harvard study that I was referring to. Is there anything that you've seen that says that there's a physical limit on like that we have to actually die? Like, can we ultimately live to 200, 250? Well, of course we can. There is no law that says we have to age. Right now there's a limit because that's what we've seen happens. But the people that live over 100 typically don't take care of themselves.

A lot of them smoke and some of them smoke and drink and don't eat good food. So what happens when you have great genes, which is 20%, plus people who do the optimal lifestyle and take the optimal supplements and take the optimal drugs,

There's no reason why 120 needs to be the maximum human lifespan. There is nothing in biology that says that there is a limit. And there are many species that live a lot longer than us, not just trees that live thousands of years, but warm-blooded mammals.

Take the bowhead whale that can live over 200 years. That's very similar to us. Our genes are almost identical compared to a banana and a yeast cell. These are living, breathing mammals with milk and they're conscious beings and they live two centuries or more.

Why can't we? We just need to learn how they do it. And I think it's all about slowing down these scratches, slowing down that clock. And we know that by looking at whales and other species that live a long time, the ticking of that clock goes very slowly. Now, they don't have supplements. They don't have to do the kind of things that we do. We're trying to hack our bodies right now to give us some of the benefits that whales naturally have.

Do you think that you will see a person live to 150 today? Oh, gosh. I think the odds are against me. But I do think that somebody born today will live that long because the technology is just going so quickly. And remember, they're going to live into the 22nd century. Who knows what that's going to be like? We can only imagine. I would like to. I'm not in any rush to leave this planet. I'm having a lot of fun. I think I'm helping people, doing my best at least.

But, you know, realistically, and nobody's asked me that question, Shane, but honestly, I think the chances of me making it beyond 150 are slim. I was born probably one generation too early.

But our kids and their kids are going to reap these benefits that we're talking about now. When you think about it, what's your expectation of your age realistically? Well, you know, I haven't set a goal. You must have one though. No, I don't. I mean, I'm not worried about my own death. I mean, I'm not a fan of being a burden on my kids or suffering, but I really don't mind if I die tomorrow. I'm not going to cry about it, obviously. But I live my life like every day is a blessing and I'm happy to have every day.

And I wouldn't say no to a thousand years. A thousand years isn't that much actually, geologically speaking. I'm 50 years old now. That's just 20 times my lifetime. 50 years went by in a blink of an eye. So what's 20 blinks? Not that much. So I would love to live centuries. I don't think it's likely. I think eventually people will. I have high levels of the FU gene and I do like to show the naysayers to be wrong.

And I would love to be able to live to 130 just so I could say, hey, remember when you said it was impossible? And that's my rebellious gene in me. But no, that's not why I do this, obviously. Although I do joke that I've had plenty of naysayers and enemies over the years. And I do like to joke. And it's actually a joke. I don't believe this. But it is fun to think about that one way of...

getting ahead of your enemies in the naysayers is to outlive them. And there is a little bit of truth to that, that science progresses one funeral at a time. And as the old God is dying off, we're seeing more rapid progress in the way

scientists and doctors think about what we can do for patients. Have you thought much about the implications of living longer and what that means for society and housing and money and fiscal policy and politics? Yeah, it's important. I think about it a lot. And we need to have less impact on the planet. I think that technology can solve anything we want. We just need to put our minds to it. And that includes being

being able to grow food that isn't wasting water, using up too much land, degrading the soil. We can do this. We have the knowledge. It's just a matter of investment and willpower and incentives and capitalism being, you know, conducive to making that happen. But yeah, we waste a lot. Half of the food in the US, by the way, is thrown out. So to say that we have a food shortage is ignorant of that fact.

But what we want to do is to produce food and not throw it away. And that's one of the reasons I've focused recently on shelf life of vegetables. But that's just one small part of a whole load of things that needs to happen. One thing that always comes up from a crowd that I would talk to about this is what about overpopulation?

And if you do the math, it turns out that even with slowing down aging and making us live to 120, we're not going to overpopulate. We're going to level out at about 10 billion people, whether we live longer or not. The big impact is reducing fertility or fertility rates, birth rates. And that's plummeting across the planet, particularly in the developing world. And already in the developed world where you and I, Shane, live,

US, for example, replacement rates of children are now negative without immigration. That's true for Europe. It's true for Australia, Japan, really bad for that, bad for the economy that is. And China increasingly worried about replacing their population. So staying alive for longer in a productive way, not an unproductive, healthy way, but productive people who have wisdom, who have knowledge,

and who can impart that wisdom and be leaders of the community rather than burdens on the community, that's a massive change that we will see probably in our lifetimes of people being centenarians and still running companies that will come back in trillions of dollars in benefits to the economy and just the US economy alone.

My hunch is that we're going to, if you could live to 120, like, I feel like we're just going to leapfrog things, right? Like we're not going to go from average lifespan of 80 to 81 to 82 to 83 to 84. I feel like we're going to go from like 80 to 110 to like 150 because technology is also going to progress over all of these years, right? So if you get the first wave of this, you might actually be able to ride the tech

technological boom to over 200. Yeah. It's a fact that for every year that you stay alive, you get to tack on another three months of life, but that's going to change. We're going to get an extra four or five, six months of life. If the age reprogramming work that Altos is doing and I'm doing works, you could get an extra year of life every birthday. And what does that mean? That's a very interesting world for

Now we can measure the blood clock. There are treatments that include stem cells. There's some hormones, so DHEA, metformin, growth hormone combination.

and others that I'm aware of not yet published, that purport to reverse aging more than a year in a year. There was a publication just now of a molecule called alpha-ketoglutarate. That molecule seems to control the clock that, according to this blood clock, sent people back eight years in age biologically in just seven months. Now,

There's a lot of skepticism. It needs to be repeated. But even if that's partly true, we are going to be in a very different world where we can control the age that we are in a way that we only dreamed of. That's beautiful. Thank you so much for your time today, David. This was a fascinating and insightful conversation. It was great to chat. And I thought the questions you asked were really spot on. And I thought our conversations can be very useful for a lot of people. Thanks again.

Thanks for listening and learning with us.

Till next time.