The Joe Rogan Experience - #1234 - David Sinclair

Episode Date: January 29, 2019

David Sinclair, Ph.D., A.O. is a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. He is best known for his work on understanding why we age and how to slow its effects. https://genetics.med.harvard.edu/sinclair/people/sinclair.php

Here we go. 5, 4, 3, 2, 1. David. Joe. How are you, sir? Great, thanks. Thanks for being here, man. I appreciate it. Thanks for having me on. Really looking forward to talking to you. Very much so. This is a fascinating subject for me. Anti-aging.

The idea that you'll be able to stop aging or even possibly pull it back or at the very least slow it down. What do you think? I think that's all on the table. We've been doing this for years in the lab. Now we've just got to figure out how to do it in people. When I talk to someone like you as an actual research scientist and this stuff, I always want to know, what are you doing to yourself? Ah, how long have you got? Like, what do you do on a daily basis?

What do I do? First of all, are you 100 years old? I'm getting there. How old are you? Turning 50. You're turning 50? Yeah. Hmm.

I wouldn't have thought you were 50. I would have figured you were for about 41, 42. Well, that's kind of you. Well, my brother's the negative control, and he's... Does he look like shit? Well, I can't say that, but people say that he doesn't look as young as me, and he's about three and a half years younger. Oh.

So what are you doing personally? Well, most of the time I'm in the lab and trying to run a bunch of companies to make these drugs a reality. But daily, I try to keep a healthy weight. I do intermittent fasting, which is pretty easy because I'm so busy I forget to eat. How many hours do you give yourself every night? Well, I suffer from late-night snacking, but I try to skip breakfast and even skip lunch if I'm busy. So I'm a night eater.

But that seemed to be good because a study came out about a couple of weeks ago, at least in mice, that it's not what you eat, it's when you eat that's most important for longevity. Really? And when being when you eat that's most important for longevity really and when when being when like what's best it doesn't actually matter uh if you eat a lot in the morning or a lot at night i like nighttime eating but you need a period during the day at least if you're a mouse probably if you're a human where you're hungry and that puts your body in a defensive mode and these are the things that we've been studying in my lab for the last 20 years. What are the processes that diet and exercise

do for us that keep us healthy? And why does calorie restriction and intermittent fasting make animals live so much longer? And we think we've figured out a large part of how that works. And now we're mimicking that with molecules.

Is the idea that you can mimic it with molecules and it will be as effective as intermittent fasting? I think the molecules will be better. And not only that, when we add them on to a healthy diet and exercise in the animals, they do even better. It's like a supercharged mouse. Now, when you add them on to the mice,

do you also add them on with intermittent fasting? And is there an additional benefit? We do. We do. We do. One of the first molecules, infamous molecules, that we are known for is resveratrol from red wine. That molecule, discovered it in my 30s, or at least linked it to aging. What we showed was that if you give it to a fat mouse, they're as healthy as a thin mouse.

They live just as long. They didn't get heart disease and all of the other bad stuff. Then what we did was interesting. We gave it to the mice either every day in their food or let them skip a meal every day so that they were fed every other day. And that combination of resveratrol plus every other day feeding, we had the longest lifespan we'd ever seen. And so it was additive. Same with exercise. If we give our latest molecule called NMN to a mouse and we exercise it, it'll run even further than it could with either of those alone.

So it's not an excuse to sit around and just eat chips and watch TV. It augments a healthy lifestyle, gets you further than what you could get naturally. So are you seeing a benefit in addition? So is the idea to compound all those things together? Exactly, right. So you asked about myself. So I do, I eat healthy. I try to skip meals.

I also take supplements. And in fact, most of my colleagues are in the field of aging or anti-aging, as people call it. So I take NMN every morning. What is NMN? Good question. So let me take a quick step back. So about 20 years ago, Lenny Garanti and a team of us at MIT discovered a set of genes that controls aging in yeast cells, just brewer's yeast, what you find in beer and bread. And those genes are called sirtuins, and there are seven of them in our bodies, five in yeast.

And what they do is they protect all organisms on the planet, plants, bacteria, humans, from deterioration and disease. They're like the Pentagon. They sense when we're hungry, sense when we're exercising, and they send out the troops to defend us. So when you put more of these genes into a yeast cell or a mouse, they'll live longer, between five to 20% longer. And so we think that these genes are responsible for the effects of dieting and exercise, which is great. What that means is we can now mimic that with molecules. So NMN is one of those molecules. So is resveratrol. You can think of resveratrol as the accelerator pedal for the sirtuin genes, and the NMN is the fuel. And without fuel, resveratrol won't work, so NMN is the gas in the car.

I've heard of resveratrol, but is NMN a new molecule? Is this commercially available? Some people have started selling it on the internet. The fucking internet. It's related to NR, which is sold by a bunch of companies. NR? Yeah, nicotinamide riboside is a supplement that raises the levels of a molecule called NAD.

I feel like I should make a shopping list. So that you get a pen. So why are you writing that down, Joe? So the sirtuins, okay, get this. So sirtuins need NAD to work. Without them, they don't work. In fact, if you don't have NAD in your body, you'd be dead in about 30 seconds. It's a really important molecule. But as we get older, we lose NAD. So by the time you're 50, like I almost am, you have about half the levels of

what you had when you were 20. So that's not good. And these sirtuins, they don't protect the body without high levels of NAD. So what NMN does, and this other molecule called NR, which both you can get on the internet, they boost the body's levels of NAD back up to youthful levels again. And if we give them to mice, these molecules to mice, or even to worms or yeast, they live longer and they're super healthy. Now, what level, like how many milligrams are you taking of these things? So, yeah, NMN is something I get from myself.

I'm not selling anything. So I take a gram of NMN in the morning based on clinical trials. It's been shown that that will raise NAD. With or without food? I take a little bit of yogurt that I make myself at home just to settle me. Yeah, I've been doing this for a while. And I only start doing stuff when I see it work in animals first. So take the yogurt, mix in some resveratrol.

Resveratrol is great, but it's really insoluble. It's like brick dust. So in the yogurt, it'll dissolve. Take another half a gram of resveratrol. And how much? Half a gram? Yeah. It's a powder.

I have a few kilos left over from clinical trials in my basement. So yeah, that's going to last me a few decades. And then I also take at night some metformin, which is probably the most radical thing that I take, which is a prescribable drug for diabetes. Metformin? Met. Met, M? M-E-T. And prescribable drug, But you don't have diabetes.

I do not. But you take it for? For preventing cancer, heart disease, Alzheimer's, and aging. Can you spell it? M-E-T. F-O-R-M-I-N. And so out of studies of 10,000 people and more, it's been shown that people who take metformin,

even if they have diabetes, are protected against other diseases of aging, even frailty. And so most scientists, if you ask them in my field, will say, yeah, metformin is likely to extend your lifespan. It's just that the FDA doesn't let you have it for aging because aging isn't a disease yet. So do you have to get diabetes to get it, or do you have to get a sneaky doctor?, or do you have to get a sneaky doctor?

Well, I wouldn't call it a sneaky doctor, but the doctor typically has to be convinced because they don't keep up with the literature, and it's off-label. Okay. And how much do you take of that? I take a gram of that as well, which is about a low dose. Some diabetics take two grams, so it's not crazy amounts. Is there any side effects? Well, the good news is that it's extremely rare that you get sick from any of these molecules.

In millions of patients around the world, nobody's getting sick. The worst you'll have, as far as I can tell, is a stomach upset. And I get that, which is actually helpful. If I'm hungry, I lose my appetite. But I think the downside is extremely low. And the upside is, anything's better than what's coming. And what is the mechanism that metformin is operating? Okay, so that so this is the great thing is that over the last 20 years, we have figured out we scientists have figured out that there are universal regulators of aging, from yeast to

worms to mice and in humans. And there are three main pathways that we figured out respond to what we eat and how we exercise. And one of them is called AMPK, and this is a target of metformin. And so when I take metformin, I'm activating my AMPK, which will send out the troops. The sirtuins I've mentioned, that's the second of the pathways. And so I take NMN and resveratrol for that.

And then the third one is called mTOR, which is a pathway in the body that responds to how many amino acids, how much meat you're eating. And it will also protect the body if you tweak it just the right way. And there's only, besides eating low amounts of protein, the only way to affect that pathway is with a drug called rapamycin, which is a little dangerous to try and is used for immunosuppressants. So it's not something that I would recommend and I don't take it. Wow. So this is your daily routine along with what kind of diet do you follow?

Well, I try to not eat too much. It's pretty easy to overeat. So I try to skip one or two meals a day. I avoid sugars and carbs. I try to run once a week. I do workouts on the weekend. Like you, I love saunas. I like to put my body in some temperature stress. So I go heat, and then I jump in a cold bath, back and forth. That works well for yeast. We can do that in the lab, and they live 30% longer. So there's all that.

But generally, I eat normally. Do you ever try going from sauna to cryotherapy? No, I haven't tried actual cryotherapy, just to... Oh, you haven't done it at all? No. You want to do it today? Sure, have you got one? Yeah, yeah, yeah. We'll take you.

Cool. Take you down the street. There's a great one, because there's different kinds, and some of them are from the neck down, where they're using liquid nitrogen. The other ones, they actually freeze the air. So when they're using the nitrogen to freeze the air and they're pumping in air that's 240 degrees below zero and you're going to do about two minutes.

I do three because I do it all the time. But it's awesome. I do three and then I take 10 minutes off and then I go back in for another three. Yeah, it makes sense. And what you're doing to your body when you do that, we think, is to activate these longevity pathways like the sirtuins. Yeah.

And that's really the trick, is to activate your body's defenses against aging. I mean, the old theories about aging, you've got to throw them out. Most people at parties will tell you, oh, antioxidants, free radicals, DNA damage, or mutations. That is all, for the most part, incorrect. That antioxidants cause DNA damagena damage no that's true that it repairs dna damage well antioxidants have been a rather big failure in the aging field but resveratrol is an antioxidant correct uh it's a mild antioxidant but it doesn't work by being an antioxidant what does it work what is the pathway uh it steps on the accelerator pedal of these sirtuin enzymes. Oh, okay. And so it's directly controlling the body's defenses against aging. So as we discussed it, or as people discussed it as an antioxidant, it was just a mild form of antioxidant, but it did so much more.

Right. And we know this because if you create a yeast cell or a worm or a mouse and then you knock out the gene for the sirtuin, now resveratrol doesn't help the animal anymore. That's interesting because when people talk about wine, that's the one thing they say, the resveratrol is an antioxidant. It's really good for you. Yeah, this is one of those urban myths that never goes away and still fuels a billion-dollar industry. But what we're finding is that the molecules in plants, like resveratrol, first of all, we think they're produced by plants because the plants are benefiting from the stress.

We call it hormesis. A little bit of stress is good for you. What doesn't kill you makes you stronger kind of thing. And hormesis was discovered about 60, 70 years ago when people were spraying herbicides on plants, and a little bit of herbicide actually made them stronger. And we think that these molecules in plants are similar. They make the plant stronger during times of stress. So if you stress a grape that's for wine making, you'll get great wine, but you also get a lot of

resveratrol. And so when we ingest that resveratrol from the plants, we get the same health benefits because the plants are activating their sirtuin pathways and we have the sirtuins and they activate us as well oh interesting interesting so low carb low sugar um any specific type of protein do you limit your amount of protein yeah i mean i i enjoy eating mammals just as much as anybody but um i try to avoid them um for the them for two main reasons. One is that there's this TMAO molecule that seems to cause heart disease. TMAO. Yeah. Yeah. And how is it linked to heart disease?

Are these epidemiology studies? I forget, but I do recall that the study was able to give the TMAO to animals and they developed heart disease. So it's somehow causing it. I forget exactly how. It might be damaging the genome. That's my recollection. With omnivores or predators? I think red meat is the culprit.

Right. So are they giving this to rats or are they giving this to… It was a mouse study again. So, I mean, mice might be different from humans, of course. It was a mouse study again. So, I mean, mice might be different from humans, of course. But the other problem with meat in general from animals is that there's a lot of amino acids in there, and it's easy to eat a lot of meat. And so if you have high levels of amino acids, it will activate this mTOR pathway, one of those three longevity pathways.

And you don't want that. You don't want that. You don't want that because mTOR has evolved to sense times of adversity and stress and hunger. So why do people see a performance benefit when they consume branched chain amino acids? Really good question. So in the short run, just like taking testosterone, it will give you performance benefits. But we think in the long run, it will actually come back to bite you. So how will branch chain amino acids come back to bite you? So branch chain amino acids will activate the SEMTOR pathway. And when we do that in animals, we actually reduce their lifespan.

So it's the opposite. You want to keep those levels low. That's interesting. That seems, I mean, for a dummy like me, it seems counterintuitive because what's making you perform better currently, you would think, especially something like amino acids, a natural part of the human body, you would think that that would be beneficial. You're adding to your body something that it needs. Yeah, you would. But what you should consider is that it's a trade-off. There's a theory that's probably correct. It's some Tom Kirkwood's theory called the disposable

soma. And our bodies want to do one of two things. We either want to grow really fast and reproduce fast, build up a lot of muscle, cells divide. That's great in the short run. You know, you'd be fertile, you can run, but actually that's at the expense of hunkering down and building a long-lasting body, and that's a trade-off over time. And so animals that grow fast and reproduce fast, like a mouse, will only have a short lifespan, whereas a whale that grows slowly and reproduces slowly

will live a long time. Interesting. So the idea is you're limiting your calories, you're limiting your carbohydrates, you're limiting your protein, you're limiting your amino acids, but you're ramping up on all these beneficial molecules. Right. These pathways that have evolved since the beginning of life To make us live longer during adversity So we can thrive when times come back Do you take into consideration quality of life versus length of life?

Like is there a sweet spot? Yeah, well it's hard to ask the mice how they feel But we do test them and we do frailty studies And we can see that they've got better memory and they can run further on a treadmill um they're stronger those kind of things they see better and uh you know we think that that probably means they're happier as well and um when you're taking in protein so if you're not eating mammals are you eating a lot of fish yeah fish is fine um white meat i indulge uh i like chicken that kind of chicken's fine um

not too much of it but i'm trying to eat as many vegetables especially the the colored ones for the reason that i said which is well a few reasons one is that you don't ingest as much protein as you otherwise would uh you get all the vitamins but you also get those molecules from the plants that we think make you healthy. So resveratrol is just one of a bunch of polyphenols that plants make when they're stressed. And when plants are stressed, they go colored. So the purples and the reds and the blues, yeah, those are molecules that are generally healthy. And I think, I'm one of the few scientists who thinks this, but I think that we've evolved as animals to sense the plant world. And when our food supply is stressed out, then our bodies sense that. When we ingest them, we get these molecules like resveratrol.

And we've evolved to sense that, and we get the benefits of longevity as a side effect. So, this is really fascinating to me because the idea that you're trying to balance out the concept of a mouse growing very quickly but dying quickly as well versus something that can extend and live longer and be more vital or have more vitality for a longer period of time. have more vitality for a longer period of time. Well, so here's the great thing is that now that we believe we've figured out why, not just why, but how this all works, what are the genes and pathways in the body that control this, we can have our cake and eat it too. We can, at least in a mouse and probably in a human in a few years' time, and maybe even with these supplements, we'll see, we can trick the body into being hungry and being in adversity even if you're eating a lot or you're not exercising.

And so we're slowly but eventually turning a mouse into more like a human so that even though you can grow and reproduce quickly, you still turn on these protective pathways and live a long time. The best example is the nematode worm, C. elegans. It's been studied a lot for longevity. And the mutations that make those worms live sometimes two and up to 10 times longer are activating genes that are normally only turned on when they hunker down and turn into a little dour stage, which means that they're not really reproducing. They're just hibernating.

So you can have a hibernation of benefits but still live a normal, healthy life. And this is from manipulating genes? Right. So this all comes from genetics. So I'm a geneticist at Harvard. And the way the breakthrough came, so going back in the 1980s, it was antioxidants, mutations, because people really didn't have a handle on what was going on. And the idea that you could slow down aging with one gene or one drug was ludicrous because it's so complicated. But now we know from genetic studies

is that you can find mutations, hundreds of them actually, in organisms that lengthen lifespan. So it's not as complicated as we thought. What about myostatin inhibitors and the studies that they've done with mice? They turn them on and off and they've grown those super mice, Hulk mice. Well, being a Hulk doesn't mean you'll live longer. Right.

But didn't they live longer though? I don't know. Did they? I believe they did. I think that was one of the weird side effects. Well, if you allow me to speculate as to why that might have happened. So being bulky is good.

Let's find out if I'm correct first. Yeah, do you want to check it out? Jamie will pull it up. Well, one of the things is bulky is good. Bulky will increase your metabolism. It will get rid of the fat. And the fat is a real problem because fat will make you inflamed. Being fat is one of the worst things you can do.

You just fat shamed. I did. And people are very, very upset at you right now. Well fat is one of the worst things you can do. You're just fat shamed. I did. And people are very, very upset at you right now. Well, build up muscle as well. Some people are overweight and have a lot of muscle and they're a lot better off. When you teach classes, I assume. I teach at Harvard, yeah.

And when you say that fat is bad, do you get a new reaction over the last couple of years? Or do you find a way around saying it like that i generally get okay comments on my lectures but i wasn't saying fat people are bad i was saying having fat in your body cells are bad right okay i like what you're saying so you're breaking it down to cells you're not picking on anybody yeah here myostatin insufficiency produces 15 life extension in mice so yeah so those myostatin insufficiency produces 15% life extension in mice. So yeah, so those myostatin inhibitors make the mice grow longer. So you think that might have had an effect by virtue of the fact that they're more bulky

and they have more muscle tissue and they burn off more fat? That's one theory. The other thing would be that some muscles are secreting molecules called myokines into the bloodstream. And we don't know what they all are, but when you exercise, you do release some of these, and they may also be contributing. Because muscles are signaling to the whole body. When you go for a run, it's not that your muscles get an exercise. Everything in your body gets an exercise by these communication molecules. And that's why if you fuse an old mouse to a young mouse, you can have these benefits that the young mouse imparts on the old and actually negatively vice versa.

And when you say by fuse, you mean by taking the blood of the old mouse and putting it into the young mouse? Right, but what we actually do, because that's too hard, you can do it in humans, but in mice what you do is you sew the skin together so that the blood flows between them. Yeah, it's not so pleasant, but they don't seem to be too badly affected once they learn how to walk in sync. Jesus. Now, by the way, to all your listeners, we don't do those experiments in my lab, but when I say we, I mean we scientists. Yes, the scientific community as a whole.

What are your thoughts on, if you have any, about the startups that are actually taking the blood of young people and injecting it into the bodies of older folks? So I don't think there's a scientific reason to say it won't work. And the scientists who are involved are some of my great colleagues, very smart people. Have you ever done it? No. It's a bit extreme for me, but I think it could work. It's just a little bit out there for me. But what they're going to do, what they're doing actually is treating people with neurological disorders. A lot of these startups I'm involved in probably 15 startups right now.

What we're trying to do is to treat diseases of aging and even rare childhood diseases because you can't treat it aging as a business model. There is no disease called aging yet. Right. But anyway, getting back to the science, I think that it's based on sold science. But the future is, I think, a better way to go about this is to find what the actual molecules are in the blood and just make those. Don't give the whole kit and caboodle. Yeah. are in the blood and just make those don't give the whole kitten caboodle yeah when you've said this twice you think aging is a disease or maybe perhaps should be treated as a disease or

classified oh i absolutely think aging should be classified as a disease we should think of it as a disease i mean why why shouldn't we everything else that goes on in the body over time that's bad for us is considered a disease do you know why aging isn't considered a disease? Because it happens to everybody? Exactly. That's the only reason. Well, it happens to most people, 90% of people in the developed world. But why is that a reason to say, oh, it's natural, we should just deal with it?

We used to say that about cancer, and we used to say that about dying from an infection. When you say it happens to 90% of the people in the developed world, what happens to the other 10? They die? Hit by a bus, I guess. Oh, okay. I see what you're saying. So they die young. Yeah.

Okay. Just clarifying. Yeah, I agree. I mean, dis-ease, it's a problem, right? Aging's a problem. I saw an old gentleman yesterday, and it was painful just to watch this poor guy walk, hunched over and just struggling to move at an incredibly slow pace. That seems like a person with a disease.

Well, it is. And imagine if we were on a planet now or an island where everybody lives 300 years, and we'd show up, and you and I in our midlife, we're starting to look old already. They're going to look at us and say, what is wrong with you guys? We need to treat you urgently. We need to call this a new type of syndrome. And it's only because we all tend to go through this that we think it's acceptable. But I would argue it's the biggest threat to the health care system. It's the biggest threat to the world's economy actually is the

inability of us to treat people in their old age and keep them healthy now some people look at it a different way and their consideration is that there's an overpopulation problem as it is and folks like you want to want to walk around living to be 300 years old and have a gang of kids. You could create a mess. All right. Well, I have three kids, but that's enough. That's more than I was going to have. But, yeah, you have to do the math, though.

How much would the population grow? I'm actually working with a number of people to try and calculate this, a couple of economists in London that we're working on. So this is really a problem. I agree with you that if this comes, and I would actually say when this comes. When this comes. I mean, it's coming. There's dozens of companies working on drugs. The science is here.

So let's say it's coming anyway. So we have to deal with this. How are we going to deal with it? Well, let's first of all understand what the future looks like we can't look backwards all right because no one's ever invented this stuff before so we have to look forwards what's the world look like um in terms of population it's not as bad as you might think if you stopped aging today and everybody just went on um forever the population growth rate would be less than the rate of immigration. Now, that can't go on forever, of course.

But what we find is as people are healthier, especially in developing nations, they have fewer kids. So the calculation shows that it would eventually taper off. So the human population will taper off about 9 to 10 billion people and then stay there. And that population will be the happiest, healthiest people people and then stay there. And that population will be the happiest, healthiest people in the world. Now, how do they predict that? Because I was having this conversation with someone the

other day that as people become more affluent and society becomes more urban, people will have less and less children and the population will stabilize. Is that the theory behind this? Right. Well, actually, education is a major part of that as well. Yeah, women's education is the main thing. But also just being healthier lifts the wealth of a nation. And by women's education, do you mean extended education so that they pursue careers?

Is that the idea? I mean, obviously, most people understand how babies are made like where where's where's the education contributing to a lower population well so my understanding is that the the first thing you do if you if you educate young women is that they can make choices for themselves and they're not just subjugated uh you know most men uh would like to have more so right so you're thinking of like third world and right the real developing world But that's where the population is a real problem in Europe. They actually are struggling to keep up with their population You know what they've got a an aging tsunami so to speak same with Japan the average farmer in Japan is 65 years old

They got a real problem China's about to head that way too and that's gonna drag the economy of the planet down and it's gonna be a real problem We're gonna waste so much money on keeping older people alive for the last 10, 20 years of their life with dementia, frailty. That could be trillions of dollars, just $50 trillion just in this country alone, that could be spent on figuring out how to solve global warming, better education, the environment, saving the one-third of species that are becoming threatened. That's why I think tackling aging isn't a selfish act. It's probably the most generous act that I could give the planet.

That's an interesting way of looking at it. What populations as a whole, when you look at the world, where are the people living the longest and why? Well, it's debatable. There are these blue zones. I think many of your listeners will have heard about those. But there are pockets that have great genes, but they also have great diets and lifestyles. And so the best one that I'm familiar with is the island of Okinawa in Japan.

And by the way, I used to follow the Okinawa diet. A couple of my good friends wrote a book about it. So I was on tofu and some fish. Felt really great. Couldn't keep it up. But those... Why couldn't you keep it up? I had kids and our meals turned into pizzas and pasta. Yeah, unfortunately.

But I'm getting back there now that my kids are teenagers. But the Okinawans, they live into their hundreds fairly frequently. It's not one in a million. It's more like one in, I think, 100,000 or something. So it's 10 times higher. They work most of their lives. They're physically active. They fast a lot, and they have a lot of green leafy vegetables.

And that seems to be the secret. And there was something about their mineral rich diet Remember they were selling It was like a big thing for a while Coral, calcium And they were using that as an example Of why the Okinawans were living so long Do you remember that kind of fad?

I do remember it Yeah, but in scientific circles We weren't really bothered with it Yeah, like there's Calcium is calcium, right? Yeah, I don't know much about it. Yeah. Like there's, calcium is calcium, right? Yeah. I don't know much about it. Better calcium from coral or something.

I might even be wrong about that. But I just remember reading about the Okinawans and the speculation. They eat seaweed as well, right? They do. Which is very healthy. Probably the best thing that they do is

they don't overeat. Stop at 70%. Yeah, I'm a glutton. That's my number one problem. I just love to eat. Yeah, me too. And I keep going. Once I'm in it, I just want to keep shoving it in my face.

But I've done a good job over the last few years of tapering that off. And the intermittent fasting, I think, is probably one of the best things I've ever done in terms of just maintaining energy levels, maintaining body weight, that kind of stuff. Yeah. Yeah, you look good. So I think that that's one of the best things that people can do. What we've known for 70 or more years, actually, is if you calorie restrict animals, actually even yeast cells and worms, they live longer. And this is the most robust way to prevent cancer,

heart disease, Alzheimer's in a mouse. And so the intermittent fasting is just a way of mimicking this calorie-restricted diet. So what is calorie restriction? It's reducing what your doctor would recommend for your body, but reducing it back to about 20% to 30%. So it's quite extreme. That's not pleasant. I tried that for a week, gave up too hard. But intermittent fasting, like yourself, it's doable. It's not always pleasant, but I think that's the best way to do it. And with the mice, it works just as well as calorie restriction, which is pretty much always being a bit hungry. Now, what other things are you looking at in terms of mitigating stress or like what other

factors are there that you have to keep an eye on? Yeah, stress is a bad one. I try to take life in my stride, not get too worried about it, remember what's important. So my heart rate rarely goes up, even under really extreme circumstances. And that's about it. I try to balance my life as best I can. I don't go through airport scanners as much as I can and have x-rays, these little things. Do you think those are bad for you?

The new ones, aren't they like a radio wave? Yeah, they're millimeter radio waves. I don't want to take any chances and also don't want to freak people out. But the old style ones that were banned in Europe first, they were potentially damaging. X-rays definitely try not to have as many as you can. But flying is just as bad as an X-ray, isn't it?

Well, that's the problem. I was going through a scanner and I said, I don't want to go through the scanner and they got quite upset because it's a bother. But they said, you know, it's just as much damage to your body as the flight. And so I said, why do I want to double it? Anyway, so I go through scanners, but I try not to. But let me tell you why I think it's so bad. Because scanners are going to change what we call the epigenome. Now, a lot of people haven't heard of the epigenome. what we call the epigenome. Now, a lot of people haven't heard of the epigenome. The genome, everybody knows, it's your DNA, the code of life.

The epigenome is what regulates and reads those genes at the right time. And so we knew about DNA. We know how to read the genome pretty easily. We can do that now on a Mars bar-sized device in a day. The epigenome is quite different. The epigenome is the structure of how the DNA is looped around. If you look at the chromosome, you're not seeing the genome. You're really basically seeing the epigenome. And what I think is causing aging

is not that you're losing the DNA structure. You're not having mutations. You're actually changing the epigenome, which is the reader of the genes. To put it another way, compact disc, okay? For the young audience, compact discs are little things we used to put music on. But anyway, these are digital information, of course. And the reason we switch to digital in the first place is that it's very copyable, and it doesn't wear out. Whereas a cassette tape, you know, people our age know that if you try to copy that a thousand times, there's not much left at the end.

So the compact disc information is the genome. The epigenome is the reader of the CD, that little laser that goes around. And what I think is causing aging is not the loss of the digital information but it's the reader, the analog part and that's like a cassette tape that eventually runs out. What's going on really is that your cells are losing the ability to read the right genes the way they did when you were 20 and that's basically noise, informational noise that gathers over time. And so what we end up with when we're 80 is a compact disc or DVD that's scratched.

So the reader cannot read the right genes at the right time. And the cells become dysfunctional. Now, what we're working on is how do you polish that CD or that DVD to get that information back again? And if you can do that, I think that's really the best way to reset your age. And we haven't published it yet, but we're working on ways to actually reset that genome and actually get back the information that we once had when we were 20. So what is happening to the epigenome when you're going through those scanners? Well, so what we found is the biggest disruptor of the epigenome is a broken chromosome, a DNA break.

And I don't know about the scanners, that's just an abundance of caution, but an X-ray will damage your DNA, no question. Even going out in the sun will do a bit of that. And we think that the cell's reaction to that break, having to unwrap the DNA from its chromatin, we call it, to unwrap the DNA from its chromatin, we call it, and then rewrap it is what eventually disrupts the ability to read the right gene at the right place. So DNA damage is essentially a little scratch on the DVD, and that accumulates over time. So being out in the sun does that,

but being out in the sun also is beneficial. Your body produces more vitamin D. Yeah, well, so there's also a theory called antagonistic pleiotropy which is what's good for you when you're young comes back to bite you when you're old so you might look good and feel good and get vitamin d when you're young but the accumulation of these scratches on the epigenome ends up you know i'm formerly an australian originally an australian i'm now american and and Australian. I grew up in the Australian sun and I can tell you that most Australians look older than they should. No ozone.

No ozone and lack of sunscreen in the 1970s. Why do you guys have a whole nil zone over Australia? What's that all about? What'd you do? No, it's what did the world do? Chlorofluorocarbons. Oh, no, you guys did it. Oh, sure. Well, hairspray. Why does it accumulate over Australia? Is there a theory behind that? It started in Antarctica. And so ozone will.

That would have been convenient. Nobody's up there. Leave it up there. Yeah, well. We need a big fan. Unfortunately, you need. Blow it that way. Yeah.

Well, yeah, the ozone layer is fairly important if you don't want to get singed by UV light. Yeah. Yeah. Well, that's one of the first things I noticed when I went to Australia was there's all these sun cancer warnings, skin cancer warnings everywhere. Well, a third of Australians get some form of skin cancer. That's crazy. Yeah. But what's also going to happen is it'll disrupt your epigenome over time and you'll look old.

But if you have an X-ray, you're going to damage your organs. You're going to accelerate aging, I believe, in your body. And you can't avoid double-strand breaks, broken chromosomes. This happens all the time. There's trillions of cells in your body and it's happening all the time. So living is a problem. Flying. Flying is even worse.

But what we're working on is how do you get back that original information into the cell and make a cell not just believe that it's 20 again, but actually be 20. So what do you do? We reprogram them. There are a set of genes that we and others have found, three main ones, that when you put them into a cell or even into a mouse, they become younger again. Whoa. How far do you think you are from implementing this on human beings? Well, so theoretically...

Are you doing it to yourself already? You could do it to yourself. Theoretically. I wouldn't do that because I'm not crazy. We need to figure out the safety. I don't want to become a giant tumor. Why don't we just use it on bad people? Yeah, well... Take people on death row and turn them into 18-year-olds and go, whoa. I don't want to become a giant tumor. Why don't we just use it on bad people? Yeah.

Take people on death row and turn them into 18-year-olds and go, whoa. Yeah. Well, yeah, that would be for someone else. Someone else. Well, hopefully no one would ever do that. Why not? We're going to kill them. Here's what we're doing.

I agree with you that we want to see what happens in humans. I mean, just give them like free pizza or something they're on death row right if you're they're already murderers you want to be the first one to me come to my life death row i don't want to go into death row but i'm saying if you're going to kill somebody like wouldn't it be a good idea to like oh hey we'll give you uh four hours of tv a day so we want to shoot you up with some stuff that's going to make you younger. If I was on death row, I'd go do it. See what's up. I don't watch TV. What we do is, so we give it to old mice and we check what happens to their body. So nursing home people, do it to them. Right? Well, tell you what, I wouldn't force anyone, but

if somebody was blind or almost blind And in our studies we're recovering eyesight Really? What about to damaged eyes? Yeah Really? Yeah, so I don't want to freak out Because I know a guy who's got a significantly damaged eye from fighting Well, I can tell you what we've done

And this is work we're writing up for publication now. We've done a few things, three things to the mice. One is we've pinched their optic nerve and crushed it, which is a test for growing neurons in the eye. And we find that with our reprogramming, we can make the nerves be just like a newborn baby. They grow back. And then we also tested on glaucoma, pressure in the eye. We

increase pressure in the mouse's eye and they lose largely their eyesight and we can recover that. And then we also test old mice that don't see very well and we also seem to improve their eyesight almost back to normal. So I don't think we'll be going to nursing homes anytime soon, but what we are doing is running a clinical trial on this. And so we're looking to do that in early 2020. And the clinical trial will be on people with glaucoma or various eye issues? The plan is glaucoma first, but it could work for other damaged retinas as well, even broken spinal cords we're thinking of trying. Wow. And that's just one part of the body. Imagine what it could potentially do to the rest of us do you feel incredibly fortunate to be living in this century uh i do every day but i would love

to live next century because it's gonna be even cooler yeah but you're what's cool is you're kind of at the the tip of the spear pushing this stuff right now like you're you're gonna be one of the guys that gets to see this stuff get implemented from your actual own research where it didn't exist before. That's pretty damn cool. Better than living 100 years from now where you just take it for granted like a trust fund kid. You know? Yeah, but just imagine what you can do in 100 years. Right. Well, maybe you'll be here. Where? On the earth? Yeah, you might be well maybe you'll be here where oh on the earth yeah you might be 150

we'll see i think there's a chance someone will be well it's it's a good chance you're gonna be i mean you're the one who's gonna know well so here's my philosophy i'm not gonna let anyone try technology until i've tried it first really yeah so i was taking a pregnant pause because you're you're currently doing something like that I'm not doing the reprogramming yet that's a little dangerous

but the others I've always wanted to know first my eyesight is starting to go because I'm 51 now and like when I

like if I had to read this book I got a Nick Christakis this book if I'm sitting here reading this book if I don't have

reading glasses on I gotta do this It's a bit of a struggle. Are you going to be able to fix that? So potentially, in the mice we can. You can? Well, we don't give them books to read, but their eyesight improves. We can test that. How do you do it? There's a moving screen. No, I don't mean how do you test, or not how you test, rather. how do you improve their eyesight? We've put these reprogramming genes into a virus, which is already used to treat genetic diseases in the eye, and we inject it straight into the mouse's eyeball. This sounds like the beginning of a horror movie.

Yeah, I think it's actually... Or an awesome movie. It's the awesome part that I'm focused on. Well, if you're going blind, one injection from your doctor, and then you take an antibiotic to turn the genes on for as long as you need, and you get your eyesight back, that's not horrific at all. That's pretty incredible. How far away do you think you are of doing that to humans?

Well, 2020 will be the first safety study, we hope. Wow. Yeah, but the crazy stuff, the future is, if this all goes well, you have an injection in your vein, let's say when you're 30, and then those viruses infect your body and they sit there dormant until you need them.

So when might you need them? You might have a car accident, turn them on. You can turn them on with just an antibiotic in a drip or in a pill. Or you start to lose your eyesight, take an antibiotic. So you put them in your body almost as an insurance policy, and then you have the option to turn them on in the future. Exactly.

Wow. That's what we do in the mice. Now, with every action, we assume there's some negative consequence or potentially negative consequence, right? We always assume that, but it's not always right. So with the molecules that we've been testing for years now, like NMN, we haven't seen any downside, just longer endurance and protection. So there isn't always a downside to these things.

In fact, if you just think NMN is replacing a molecule that we lose over time as we get older it's just becoming you know it's a fairly natural process no downside exercising and dieting either right of course and you said you run once a week is that what you do and you do do you lift weights as well right and when you do it do you try to not go too hard and burn yourself out too much? Do you have a sweet spot? Yeah, I do. I do. I try not to go too much.

That's the trick with everything in life. It's this hormesis effect. Get your body damaged enough that it can repair itself but give you the benefits without like having a lot of x-rays or radiation right doing it and scratching that cd yeah that's always my thought on people that uh do extreme endurance activities like um ultra marathons and things along those lines i mean i marvel at their willpower and their ability to push themselves through that and the physical condition they have to be in to perform such feats. But I always think, man, you're probably doing X times the amount of damage to your body that a normal person does at your age. That sounds right.

Calorie restriction works, but if you overdo it, you also… Starve. Yeah, you die. So you've got to find the right balance. Right. How do you know what the right balance is for you? Good question. How does anybody? So we live in an age that is still fairly primitive. This is why I like the future. These days we go to the doctor, most of us go to the doctor for annual physical, which is ludicrous. The idea that your doctor will take a, hopefully a blood test, a prostate exam once a year, that's kind of crazy. What happens if you've got a tumor that developed

the day you leave the doctor's office? So the future, and actually partially for those who are on the cutting edge can be done right now, it's monitoring your body in various ways, genetically, epigenetically, we can measure those scratches right now. And also with blood tests, you can also have companies tell you if you're out of range, if you're not optimized, and how to get it back in order. So that's what I do. So how often do you monitor your blood? Probably every few months.

I have a blood test from a company that tells me what I need to correct. And how extensive is this blood test? Is it the standard one that a normal person can get, or do you have to have a prescription to get this? No, you can go online and get it. It's about, I think, 40 parameters they measure, some that are not standard that your doctor wouldn't do, some are pretty standard. But what's nice is it's a tracking system. It's called Inside Tracker, and you can see over time if things are going up. And even if they're not out of range yet, you can see if they're headed that direction and correct it before it's too late.

So that's why, one of the reasons I'm on metformin, my blood glucose was going up and up and up which predicts lower life. And so metformin got it back down to where it was optimal again. So that's one of the things that metformin does is it lowers your blood glucose? That's what it's prescribed for, for diabetics. Now, does that have any effect on your energy levels? I don't think so. I haven't noticed that.

Where you would notice it is during rigorous exercise. That makes sense. Do you feel it? Well, so I take metformin at night. So that may be probably the best thing. Right. So when you're sleeping, it's having its effect and it's run its course by the time you wake up, you believe? Yeah.

Now, when you are exercising, are you exercising fasted or do you take a certain amount of carbohydrates before you do any kind of physical exercise? a certain amount of carbohydrates before you do any kind of physical exercise? So I start at the gym 2 p.m. on a Sunday, and I'll have a salad wrap or something like that so I'm not feeling hungry during it and won't pass out. Huh. And so I understand that you're getting these blood tests, but do you have a trainer? Do you set a workout?

Do you structure it? I do now. Just recently got a trainer? Do you set a workout? Do you structure it? I do now. Just recently got a trainer. It's a great thing to do with your son, father-son time. So, yeah, we have an hour of trainer, and then we also do a bit of boxing. Beat your kid up? You're beating your son up? Yeah, it's fun.

It's legal, I think. Go to the sauna. That's just the best way to spend a day. That is a nice way to spend a day. So how many days a week are you doing this? Do you give yourself days off? Do you schedule that? Well, so once a day of that, once a week on a Sunday.

And during the week, if I have a chance and I'm not traveling, I go to the home gym. And when you say you run once a week, is that by design that you only give yourself once a week? I probably run two times a week, high intensity, if I could. And I try to do that. Often I'm on a plane. Right. And when you say high intensity, are you sprinting, doing track work, like what kind of stuff? Yeah.

So I'm not an expert so what i do is i i will spend a half spend about half an hour on one of those treadmills that's u-shaped yeah i got one of those out here yeah great they are so that you determine your speed so i'll sprint and then i'll slow down sprint slow down they're actually more difficult than running on the flat surface it's where regular treadmills is actually easier than running because the treadmill is moving you're just kind of lifting your legs up and keeping moving with this actually you're powering it so by you pushing on it it's actually more it's like running i forget what the degree incline is but it's like an x x amount percentage harder than a regular run oh good uh well that's what feels good to me and what although it's a little bit scary, if you're not used to these treadmills, you can run off the front because they're free-flowing. Go right off the tip.

Yeah, but they have handles. Oh, yeah. You're a genius. You're not going to go flying off the treadmill like a dummy. I'm no genius. Especially when it comes to sport. Yeah. Yeah, I'm a big fan of those things. And it's nice, too, because there's a lot of give to them. There's not much pounding when you run on those.

It's not like running on hard surface. Yeah. So I try to go easy on my joints. I've seen, you've probably all seen sports players with all sorts of damage to joints. Oh, yeah. I've done all of it. Yeah. Yeah. So, yeah, low impact, high intensity.

And as far as weightlifting, what kind of stuff you're doing there because weightlifting does have a beneficial effect on bone density and it supposedly has an effect on anti-aging as well uh yeah absolutely believe in that and so i try to maintain some muscle mass um it's good for burning fat too. So, you know, I try to do, not go overboard with the bench presses. Otherwise, I'll have even more rounded shoulders, try to get the straight back. So the trainer is helping me bring my body back into shape. He took one look at me and he said, you did this unsupervised. Yeah, you wrecked your body in your 20s. Let's try to fix that.

What did he say you were doing wrong? I said, why would you do an exercise On a part of your body you can't see in the mirror? Oh, your back? My back is flimsy And it's all here So I stand like this You're smart, man

It's protecting your spine Yeah, but I love bench pressing Oh, God At least I used to That's a great way to blow your shoulders out too, though, right? Oh, yeah Yeah, especially if you do it heavy Now um you do this how many days a week uh hopefully two or three two or three a week so all the everything you're doing you would essentially recommend to others

as well right so you think that's a good plan two to three days a week of weight lifting one to two days a week of running sauna when you can yeah so i i never use the word recommend gets me into trouble yeah good move i just say what i do when people can judge but that's smart but the science does say this is the optimal and that's why i've chosen it for myself but i think without monitoring yourself it's easy to overdo it um and also you just really don't know what's going on in the inside it's crazy crazy to think we know more about our cars as we drive on the dashboard than we do about our bodies. How does anybody know if the exercise is too much, too little, or if that supplement's doing anything? Right. That is a big problem, right? I mean, one of the things that we have a giant

problem in MMA is tainted supplements. People buying supplements and the supplements have other things in them. What are you drinking? Do you drink mostly water? Do you consume caffeine? So with NMN, which gives me a boost, I think, caffeine is a little too intense. Really? I find that. So I'll have a cup of coffee in the morning, but that's it.

One a day? Yeah. Wow. Yeah, just to kick of coffee in the morning, but that's it. One a day? Yeah. Wow. Yeah, just to kick start. How do you live? It's hard. It's really hard. But when you're doing research all the time, don't you need a little boost sometimes?

Well, I do drink Diet Coke or Pepsi. Oh, how dare you? You just ruined everything you said. You're doing that? Yeah, it's my vice. Isn't that stuff fucking horrible for you? Is it that bad aspartame well i actually had an inflated idea of how bad it was apparently and talking to another research scientist uh he was telling me that the this the actual amount that they gave to rats when they're you know diagnosing them with cancer is almost impossible for a person to consume.

So you would have to have ungodly amounts of aspartame in order to get these effects that everyone's terrified of. He said the other thing to take into consideration is look around at how many people are drinking Diet Coke. He goes, if it was really that bad, they'd be dropping like flies. The consideration, though, is upsetting your gut biome. Exactly. Right.

That I know. Or at least I've read. But he said that's also probably large quantities. It's true. But as you know, the microbiome is a finicky thing, and you don't want to mess with that. It's the reason I have this yogurt in the morning trying to reset that thing. Do you kimchi it all?

Yeah. Not regularly regularly but yeah that's that's what about other fermented vegetables or anything along those lines that give you probiotics japanese food i'm into but i don't think about my diet that often usually too busy running around but now have you ever messed around with nootropics or anything like that to enhance your mental clarity or boost your brain power? Well, yeah, my brain is always running a marathon. That's my career. I definitely notice that if I take time off, even a weekend, without thinking, I'm dumber on Monday. Dumber? Well, yeah, I just can't think.

So it's almost like you need to keep that pace going. For sure. Oh. Right, right. I guess I'm not a natural genius. I have to work at it. But I do find that constant stimulation, I've got to do that to be at the peak. And this is the tippy peak.

This is the genetics department at Harvard Medical School. These are no dummies. These are a quarter of them are Nobel Prize winners. A lot of the science we publish is in the world's top journals, which you rarely get into. So to be able to think of these ideas and come up with new things, you can't just do that on a whim. You really have to have a mind that is focused.

And in shape. Exactly. Yeah. So it is essentially you feel like running like if you take days off you actually slip back a little bit and then you have to ramp back up to speed it's horrible i really hate it but is it just because you just get used to a lazy pace and you have to like acclimate to get back in the lab or is it actually you do get dumber? I don't have the memory recall. I feel like I did when I was in my 20s, which is I wasn't as sharp. I'm a lot sharper than I was then.

So part of it could be the mental training that I give myself every day. The other part could be the molecules that I'm taking. So NMN, raising NAD, could have neurotropic effects. We don't know. Yeah, I'm sure. Creatine supposedly has nootropic effects. We don't know. Yeah, I'm sure. Creatine supposedly has nootropic effects as well. Do you ever take that? No.

Caffeine certainly does. I'd like to get you some actual nootropics. I'll send you some. There's a bunch of different ones that I use. I use three different companies. One that's one of mine and two that are other companies, NeuroOne and another one called TrueBrain. And I find them pretty beneficial. Great.

I could do with that. Yeah. It'll definitely – well, the one that we've tested was AlphaBrain. We tested the Boston Center for Memory. They did a double-blind placebo-controlled study. It showed increase in verbal memory, increase in reaction speed, reaction time. But the other one is paracetam. Have you ever messed with any of those?

No. Choline, you ever supplement with that? No. Interesting. Right. I could be smarter, I guess. Well, I don't think it's that. It's just it's not smarter.

I don't think anything makes you smarter. I think knowledge makes you smarter. What it does is it gives you access, I think, to something that's already in your head. A little smoother. Good. The recall is important. The other thing as a scientist, what you need is, you need to see a thousand different sets of data and put them into one thing and see the connections. So I'm exposed to so much information. It's drinking from a fire hose every day. I'm reading papers. I'm talking to dozens of people.

I've got dozens of companies. I've got two labs in the world. It's just coming in. And for my brain to take it in, sort it out, finds links between them, connect that person with that politician, with that person in the military, it's all going on. And a regular brain that isn't trained would have a hard time yeah i would imagine i'm so shocked that you only drink one cup of coffee a day with that kind of schedule uh well so the nmn is good um do you take nad in an iv form no no i've i haven't but i've talked to many people that have i've been scheduling it or wanting to schedule it putting it off for weeks

people that have i've been scheduling it or wanting to schedule it putting it off for weeks but uh i'm going to do that soon because i just know too many people that have extreme benefits from it yeah sounds good um do you know anyone who's done it no hmm that seems like something would be right up your alley uh yeah you'd think i've just been more focused on curing aging. But NAD does have supposedly some sort of an effect on aging, correct? IV NAD? I don't know about IV NAD. It's been poorly studied, actually. There's a lot of anecdotes, and I hear about these all the time. But I haven't seen really hardcore double-blind placebo-controlled trials. Now, NAD in supplemental form, though, in terms of orally ingested NAD? So if you give NAD to an animal or a cell, it's taken up really poorly. NAD is a big molecule. NMN is a smaller version of NAD that gets into cells quickly.

So that's probably a difference. Ah, so it's the same benefit, but it's easier consumed orally? Well, I think so. I mean, we're still at the cutting edge of figuring out what's true and what isn't, but NAD is thought to not be well absorbed in the body as compared to these other smaller molecules that the body then turns into NAD once it gets in. How much water do you drink? Not enough. Not enough.

I was just speaking with some members of Tom Brady's team, and they said, David, you've got to drink more. Tom Brady's team? Yeah. You mean his physical team? You don't mean like the Patriots? No, his CEO of his company. Oh, okay.

And they're saying you need to drink more. And you went and got to see. It's like suggestion. I'm drinking some now too. Yeah, I'm drinking a lot more. Then you end up just going to the bathroom half the time. You got to do what you got to do. You do.

You do. It makes sense to me. Having a buildup of toxins in your body and urea isn't a good thing. Right. Do you take anything else that uh is notable well i can run you through it sure i'm on a lipid a statin for why are you on a statin i've been on a statin since i was in my 20s whoa yeah hmm uh that stuff's fucking terrible for you uh right so my good friend and colleague george church uh Church at Harvard, told me I'm killing myself.

But I have really high cholesterol. My family. Genetically. Genetically, yeah. And does your family have a history of heart disease because of this? Yeah. So my grandmother, at least according to her, had a stroke in her 30s. Whoa.

Yeah. It's bad. So I'm fighting bad Ashkenazi Jew genes here. That's crazy. So you've been on Ashkenazi Jew genes here. That's crazy. So you've been on them since you were in your 20s. And you're a thin man. If anybody looked at you, they would never think that you have an issue. Yeah, it's unfortunate.

But I'm a doctor's worst nightmare. First of all, I teach them so I know what they're like. But also when I go into the doctor's office, I say, here's what we should be doing, or you should be doing to me. And so I went in my 20s and I said, I want to go on a statin. And this is in the days when statins weren't well studied. And my doctor said, but you're not old. And I said, I don't want to wait till I'm old and sick to get this medicine. I need it now. And I fought the doctor, fought the doctor, and eventually he prescribed it, and my cholesterol came down. I'm the same with dentists.

I went to the dentist a few months ago, and I said, I want my teeth fixed, my two front teeth. And she said, they're fine, normal wear and tear. And I said, I don't care what's normal. Fix my teeth, get them back to how I was when I was 20. No, we don't do that. We don't do that.

Well, you did my daughter, right, last week. Yeah, but she's young. She's got a future. Oh, they were saying you were done. Don't be ageist. What was wrong with your teeth? They were wearing out, and I hated feeling that worn out. Wearing out?

You don't get that? In what way? Just getting shorter and flatter. What the fuck are you eating, rocks? Yeah, I must be. It's the Australian diet. A lot of sand in your food yeah so i said to her uh i thought you were one of the world's best dentists and she said okay fine i'll do it but don't blame me if it doesn't work um and so she doesn't work well she was worried that uh it

might snap off or not so you're she's putting a cap on you. Yeah, she's extending my two front teeth. But that's normal. Like people get caps all the time. Well, it's not a cap. It's actually just material stuck to the tip right there. Oh, just on the tip. Yeah. Oh, so like if you had a chipped tooth, they would do that instead of replace the actual tooth itself. That's what they did to my daughter.

Yeah. And I said, do that to me. That looks great. And she said, no, no, no. Finally, she said, okay, but it's your problem. You've got to pay for it. Fine. And she did it, and she actually said at the end of it, this is great.

I might offer this as a procedure to other patients. But my point is not about teeth. It's the medical profession is ageist. They give young people certain treatments because they're young, and they don't give them to the old. But then they don't give the young people the treatments that they need before they get old. Yeah. It's wacky.

I had a similar thing happen with a torn meniscus. I have a minor meniscus tear. And the guy told me, well, if you were young, they would stitch it up and hope that it would heal. I'm like, what the fuck does that mean? I go, everything works good. Like, what is the difference between me and a younger body? And he said something about blood flow. You have more blood flow.

I said, look, I'm not a doctor, but that doesn't make any sense. I go, I'm working out all the time. There's a lot of blood going through there. Like, what the fuck is happening? And I'm like, let's just shoot some stem cells in there and see what's up. Like, what the fuck is happening? And I'm like, let's just shoot some stem cells in there and see what's up. Because they wanted to do meniscus, you know, what is it, menoscopy, whatever they call it, when they cut some of the meniscus out. I'm like, eh, let's just try.

It's totally working. Like, I don't have any pain in it now. So I think there's a weird thing that they do do when you get to a certain age. Like I have a friend who has a torn ACL, and they essentially, he's in his 50s, like late 50s, and they essentially told him not to fix it. I go, hey, fucker, get it fixed. What are you, crazy? You're going to have a wobbly knee?

And they're like, well, they told me if I was younger. Fuck that doctor. Go get that thing fixed. He's like, wow wow the recovery time like shut up you just recover you just you're alive a year goes by it's fixed just stop just go get it fixed yeah see that's the problem with today's society because we think a 50 year old is is over ill that's dead that's bs 50 is still very young actually there are 78 70 year old 80 year olds even 90 yearolds still playing tennis.

Yeah. Loving life. That's just the beginning of what's coming. If you maintain activity. That seems to be the key. The really hard thing is when someone's in their 50s and they want to get in shape now. And they haven't been active their whole life. That seems to be a problem.

Their DVD is scratched up. Yes. It's hard to go back. It can be done, though. I did see a guy who was 58 years old who started running marathons at 58. In his 70s, he's running sub-three-hour marathons, and he looks great. Exactly. So he just had to take his time and really be dedicated and watch his diet, nutrition,

and next thing you know, this guy's an elite marathon runner. It is doable. What we find in the lab is if we treat mice early in life, it gives them a much better lifespan extension. Sure. So don't ever leave it too late. Well, you see that with athletes, like athletes that were fit when they were young and never lost it,

really maintained and stayed in the gym and stayed active. You see them in their 50s and even in their 60s looking great. Whereas, you know, it's just once your body deteriorates, it's very difficult to bring it back. But if you maintain it, it seems like there's people today that are doing that, and it's much more common. If you go to a gym, for instance, go to a nice gym, you'll see a lot of folks that are in their 60s and 70s that are really active and they're there all the time.

And they're regulars at the gym and they look great. They do. So my father is a prime example of that. So he's in Australia and he's been taking care of his body since he was in his early 40s, probably a little too late. But still, he's been taking cementamine and sm cementformin for a while, resveratrol. But he's been active. That's the key, I think. And then, so that combination, so he's now just turning 80 this year.

You would think that he's 30. If you didn't know his age, he's running around. My mother passed away from cancer, so he's dating women. He's out every night. He's traveling around. My mother passed away from cancer, so he's dating women. He's out every night. He's traveling the world. Now, this is the future for people in their 80s. He started a new career. At 80?

It was at 76. What's he doing? He got bored. So he retired at 67. Thought he had another 10 years of good life, and he kept going and going and going. His friends are getting frail. He's still active. active so he went back and he's working at sydney university on the ethics panel for clinical trials and other studies and that's what you want older people with wisdom and knowledge to do to give back that sounds good too like for you you get your dad

hopped up on all these awesome new drugs then you get him working on the ethics panel for clinical studies and then you get them to give you some death row patients so you can try it on right ethics you're onto me yes i know what you're doing now man you're wiggling the system a little bit with your keep it in the family hyper active super healthy dad right well i don't recommend anything even to my family, but they end up demanding it. My brother was pretty upset that we weren't giving him any. Well, it seems like it's working out really well for your father. I mean, so metformin, the NMM, and what else is he taking?

He's also on a statin and he exercises. That's the main thing. So he's on a statin as well because he has the same predisposed condition. Right. That's an awful condition, man. One of the things that I was talking to my doctor about, he was saying that there are people that just have high blood pressure or higher blood pressure or higher instances of heart disease in their family and it's just a really unfortunate genetic issue. It is. It is. But fortunately, we're able to tackle heart disease pretty well these days with blood pressure drugs and cholesterol drugs. There are some side effects, no question. But what we're talking about with these longevity drugs that are in development

is that, sure, you can be prescribed this medicine for your Alzheimer's or for your liver disease, but as a side effect, it'll keep the rest of your body healthy as well, protect you against cancer and all these other things. That's what's so radical about what we're doing. Now, what about CRISPR? And what do you think is going to come out of that in terms of real-world application for an adult? I mean, if people don't know what CRISPR is, please explain it in layman's terms. Yeah, so CRISPR is a term actually was invented in my department partly, so I know it pretty well.

Bacteria have an immune system that cuts invaders, cuts their DNA. And what we've done now, as scientists, we've now utilized that system, take it out of the bacteria, and we use it to create designer mutations, designer gene changes in animals and also in humans. So it's a bacterial immune system that corrects genes. And we use it all the time now.

It's actually, what's interesting about it is we've been able to mutate genes for many years, but this is dial up a gene mutation. You can choose exactly where you want to make it. And so I think many of you listeners will know that recently, late last year, a Chinese researcher in our field came out and said he's engineered a couple of twin girls with crisper to be resistant to hiv the aids virus wow um if they're telling you that you gotta think they're doing some stuff they're not telling you about right well you have some kids with giant heads and well it's coming through walls reminds well yeah if you start to see people uh that are 90 and uh and they're still as young as 20 you know something's going on yeah that's the weird one right if you can you'd go hey what are you

doing nothing just eating healthy looking good take care bye that's right i'm not gonna tell you yeah yeah well so consider this that that so the chance of getting hiv in china is one in a thousand so that doctor was seemingly he thought he was ethical, protecting the babies from something that's, I would say, really rare. Whereas if you really wanted to do something helpful to those kids and we agreed it was something you should do, why not make them resistant to heart disease or to cancer? We can do that.

It was weird that he chose HIV as the first test. Why do you think was weird that he chose hiv as the first test why do you think they did that um i think because the it was a very um well understood mutation that would if you just destroyed the gene it would work whereas with these other diseases you have to be much more precise but the reason that we scientists got really upset was that he did it in secrecy and then just launched it on the world and that kind of thing, because it's a fine line in ethics, you want to be doing that with total transparency. And I think he was hoping to become, win a Nobel Prize or be a star,

and it backfired on him because he just did it in secrecy. It backfired in the scientific communities? Absolutely. In the real world, in the media, I was shocked how little discussion there was. If this news came out in the 2000s, during the Bush era, there would have been panels, investigations, it would have been in the news for months. But it wasn't. People went, what's next on Twitter? Do you think it's just because the news cycle is so insane? I do. Yeah. When you have a scientific experiment of that nature what's the

standard protocol for a scientist whether it is is it the same in china and in russia and in the united states as a scientific community almost operate under different like a different set of rules than anything else you mean between countries yes i mean you know like obviously technology is not shared like china is doing something technologically united states is they we have to speculate we have to figure it out but when it comes to medical science right is it sort of an open book is everybody sharing information uh no or at least alerting everyone to what they're working on well i know where you're going with this um at least i think i do okay uh yeah so i i advise governments um around the world about what's going on um under

the radar as best i know and there are countries i'm not going to name them um that are doing research under the radar and are preventing people like myself from entering those buildings to have a look at what's going on. So I'm sure that what's going on in there is actually a little bit broader than what we hear about. But I don't know, how long is it before I'm over? Did you just say Russia? No, I didn't say Russia. I didn't say anything. No country. I want to be able to travel freely. I didn't know how long is it before a mother... Did you just say Russia? No, I didn't say Russia. I didn't say anything. No country.

I want to be able to travel freely. I thought I heard you say Russia. Oh, I said it. But in countries where there are different standards, what's stopping a mother who wants to prevent their child from having heart disease, which could kill their child, you know, 40% chance versus one in a thousand.

And eventually, you could kill their child, you know, 40% chance versus one in a thousand. And eventually, you could make a child that could live 200 years. Once we know how to do it, that could be the future. There's always a concern that someone is doing something that is beneficial in one way, but negative in another way. And if everyone doesn't get to examine the research, it's very difficult. Like if we wanted to, in the United States, wanted to do something similar to what they're doing over there,

we would want to have access to what they've learned, right? We would. And so generally scientists share information. Right. But there are companies that are government-owned that are very secret. Right. Or even private organizations. And that's where it's a little tricky.

And that's why we scientists get really upset when companies or organizations don't share information. Especially in something this critical. Right. And what's not really stated, but it's my belief, is that one of the reasons there was such a backlash against this CRISPR designer baby experiment, and it really was an experiment. It's not just that it was potentially dangerous and you could end up with kids that have deformities. But also that unless we do this in a measured manner under supervision, there could be a backlash like there was against stem cell research in the 2000s.s we don't want that again we want to be able to do this the right way this time right is it particularly if something goes wrong with those children right one person could ruin it for millions of people right if they jump the gun and yeah so this we're on the second

generation of crisper is that correct uh in terms of uh editing tools, they've become more... They have. Surprisingly, there's a lot of different bacteria that have these systems. So we're getting new ones all the time, some that are more accurate because you don't want what we call off-target effects. You don't want to accidentally mutate some gene that's required for head development. I think in my department,'re on fourth generation now. Fourth generation. Yeah.

Wow. Yeah, see, I'm just going by Radiolab Podcasts. Yeah. So my department's a fun department to be in. I would imagine. It's amazing. They're inventing all sorts of stuff. Did you ever see the documentary Icarus?

Oh, yeah, it rings a bell. It's Brian Fogel's documentary on the Russian doping program, state-sponsored doping program in Sochi, the Sochi Olympics, and how they had this incredibly complicated system of stealing the urine and putting it through a hole in the wall and putting fake urine back through. It was really, really amazing amazing documentary but uh details this incredibly complicated state sponsored doping system i would imagine that with something like crisper or some various new forms of genetic editing, that that's one of the things that they're going to be looking into,

that they're going to be looking into things that are going to enhance athletic performance. Yeah. I mean, you might need to have a DNA test to see if you've put one of these viruses in your body. Why are you 50 and now you're running like a 20-year-old? Right. So that's all possible. I also write reports for governments,

and one of the things that I predicted within the next 15 years was CRISPR being used to engineer the human genome and make a baby. I didn't realize it was going to happen within one year. A lot of these technologies that I'm trying to predict happen way faster than even I think are going to happen. Do you think it's going to happen. Do you think it's possibly happened in other circumstances that they're not going public with? It's always possible.

There may be some human clones running around right now that we don't know about. Do you think so? It's certainly doable scientifically. There might be some rogue nation who's doing it. Barbara Streisand's dogs were pretty easy to clone. Yeah, she had her dogs cloned, right? Yeah. Yeah, Sammy, the 14-year-old dog,

there's two of them. Jesus Christ. That's so weird. I'd be so scared. I'd go to sleep and wake up, and that thing would be hovering over my face with red glowing eyes. Yeah, wait until you have designer dogs. Pet cemetery.

A friend of mine, Carlos Bustamante at Stanford we're entertaining the idea of making dogs live longer uh genetically so why would you want your family member to only live yeah 12 years I think about that man my dog's only two and he's such a sweetie you know I'm sad that one I mean, I had to put my other dog down recently, who's 13. And he's just really, he's a mastiff too, and he was struggling. And I just think, man, this two-year-old one day, he's going to be in that same sort of situation. Well, it is. And so we have three dogs. My wife runs a therapy dog organization.

Barbara Streisand had her beloved dog, Samantha, cloned. That crazy bitch. Look at her. Two copies of one dog. Jesus Christ, that's so strange how about just get a new dog you fucking nut uh well so it so we might be nuts in my household because we're giving our dogs nmn oh and how's it doing how old's the dog now good what the oldest dog is nine and he's still doing fine does he he look different? My wife says so.

These are anecdotes. I'm not going to publish them. So ours is a therapy dog, and he has to go to hospitals and nursing homes. And if he has NMN, according to my wife, he can't be a therapy dog because he's too excited. He's running around, jumping around. Really?

So that's anecdotal, but that seems to fit with what others have experienced too. Wow. Yeah, so we're hoping to have some treatments for some pets shortly, one of the companies that I'm working with. Treatments for pets. Yeah. Well, you've got to think, hey, man, dogs are only going to live 13 years anyway.

You know? Well, yeah, and also we have a dog that has a kidney defect, and the vet says it's only going to live five years. So she's three now. So that's the one you're experimenting on? Well, we experiment on all of them. But what's the downside? That's got to be so uncomfortable for some people listening to this right now. Like, oh, I don't know how to feel about that.

What is the downside? If your dog has got a kidney defect and it's only going to probably live to be nine, meanwhile that dog is going to live to be 1,000 years old. Well, we'll say I'll come back and I'll let you know. The dog is going to be in the lotus position meditating 100 years from now. What do you do if it starts talking to you? That'd be great. Yeah, what do you do if you turn a dog into some new kind of thing that lives 30 or 40 years?

Do you tell people? Like if your dog, like right now you're talking about it on the podcast and a bunch of people are probably going to remember, but a lot of people forget. But if like 15, 20 years from now, your dog's still chasing balls and people are going to come over your house,

hey Dave, what the fuck's going on with your dog, man? Is that the same dog? That's Charlie, yeah. How come Charlie doesn't have gray hair anymore man right well you know people don't have any gray hair no yeah man that's weird isn't it you don't have any that's weird right how long you been on this stuff uh well rose virtual i started 12 years ago met foreman about three years ago and a man about the same time. Wow. Does anyone in your family have gray hair? Is it a genetic issue?

My father has all gray hair. My brother's about a third gray to half gray. Wow. Has your brother taken the stuff you're taking? Only recently. Aha. Interesting. Yeah, we call that an N of three in an experiment, which is insufficient.

Right. So I don't want to get slapped on the wrist by Harvard Medical course medical schools i'm the dummy who's saying all these things you're just answering questions sir do not worry right but so far so good if i'm around in another hundred years we'll know something's odd that would be unbelievably fascinating if your dog lived to be like 30 or 40 years old that would be really incredible and if i meet you in 15 years you still have dark hair i'll be like what what the hell man um what other things are you taking do you take multivitamins uh i take vitamin d that's it with k2 just vitamin d yeah what about e or k or any of those k2 and d together and that's it oh so i'm afraid of iron afraid of it yeah why uh there's some results that i've seen that that

excess iron especially in the elderly leads to senescence of cells and build up of those zombie cells is a bad thing and is this uh dietary iron like from vegetables or is it from cooking on a cast iron pan or well i only know from correlations so i'm looking at tissue that's full of iron and the cells are not looking good so all i can think is i don't want to overload myself on iron so this is um like how much iron? Is too much iron? We don't know yet. Because I always hear, especially from women, iron deficiencies. For some reason, I hear, I've heard it from several women.

Sure. But for the elderly, overloading them with iron, I think, is a real problem. So there's a sweet spot to hit. Well, yeah, I'm sure. I'm sure there is, but the iron will damage your cells pretty badly, so you don't want to go overboard. And no other supplements? No. No, I try to eat vegetables,

which hopefully will make sure I'm not deficient in anything. Green, leafy, dark vegetables. Exactly, exactly. Peanuts. Fresh if I can. Color i can colorful straight out of the fridge instead of going for the for uh the a piece of cooked meat i'll go for a carrot or something i eat so many carrots i probably turn orange now carrots have a lot of sugar oh great now i gotta cut out my carrots well mean, especially if you drink them in the juice form. Yeah. Like, I know a lot of friends who really enjoy fruit juices and vegetable juices.

And I always say, well, I mean, vegetable juice, yeah, it's probably great. But fruit juice, man. Drinking a big glass of orange juice, you might as well be having a Coca-Cola. Yeah. Yeah, I agree. So our household has a ban on smoothies and fruit juices and sodas that have sugar in them. God, I used to be able to go to like Jamba Juice and get one of those big old smoothies and feel like you're doing something good for your body. I used to think, yeah, look at, I got all this blueberries in there and great stuff.

But meanwhile, there's just a gang of sugar in that thing. Yeah. I heard an interesting thing that that whole milk is actually potentially better for you than the the low fat because you'll use less of it and it doesn't you know milk has some sugar in it it's also attached to fat right the whole milk has fat in it and it's normal it's normal for your body to consume it that way right what what i want is i want my money back from the nutritionists in the 1970s and 80s i skipped eggs and bacon. Could have been eating that stuff.

Well, you remember that food pyramid that used to be in the Dr. Seuss books? You're teaching kids to eat cereal. It's so crazy. And put margarine on your bread. Oh, that's the best. That's the best bad advice that they ever gave. Vegetable oils, which are fucking terrible for you. advice that they ever gave vegetable oils which are fucking terrible for you all those disgusting vegetables safflower and corn oil all that stuff that's just terrible terrible for you it is the

other thing that that mothers used to and to some extent still tell their kids is don't go hungry have a snack yeah i shouldn't say mothers parents in general but in my family it's it's my wife Have a snack. Yeah. I shouldn't say mothers, parents in general, but in my family, it's my wife. She hates to see our kids go hungry at all. Right. So it's always eat, eat, eat, never be hungry.

And I'm there saying, no, be hungry. It's good for you. And it's this tension. Is that the same with children, though? Because children are growing. I always assume that children, they should just eat whenever they're hungry. Well, that's what's stated. I'm not sure if that's the case. Often my son is – so my son isn't thin, put it that way, and he'll be going out the door and my wife will say, have you had breakfast?

No, I'm not hungry. You have to eat something. And I'm thinking, no, you've got plenty of energy stored there. Don't worry about it. Yeah, I mean, it makes sense. The only thing that I think of is that when you're a young person, your body is still actually growing and developing. As opposed to you and I, if we're fasting, it makes sense, right? It makes sense you're giving your body a break and there's all sorts of proven benefits to that fasting process.

Well, if you have a child who's overweight is it a bad thing to skip a meal no no it's not the the one thing that worries me about children that are overweight skipping a meal though is that they're not as disciplined and they're not so good psychologically with struggling and and having you know uh having hunger pangs and that you're gonna fuck their head up it's true the teachers will probably be very angry with me that the kids can't concentrate well it's not just that yeah the kids can't concentrate but i just i worry that it's in some way shape or form abusive like to say hey you're overweight you need to lose weight like i don't think they're like i don't think they're really designed to go without the way a grown adult does.

These are my own perceptions. I think that it's probably far better to adjust their diet. And if you've got a kid, just slowly get their body weight down with exercise, particularly with resistance training and doing things that really burn off a lot of calories and then just get them off the sugar. And then I think the weight will slowly slip off, probably not even so slowly if you can really get them off a significant sugar binge. Exactly. So that's why I'm taking my son to the gym as well. I agree with that. I'm just, just to clarify, because I don't want a bunch of hate mail.

All I'm saying is don't force feed a kid. Yes. Yes. Yeah. Don't force feed a kid. Yeah. I agree with that. But I just think that kids, they just get so fucking hungry, man. They get, because their little bodies are like little hummingbirds, you know, they're

burning so much energy. Yeah, they do. I'm amazed you don't take any other supplements, just vitamin D. No multivitamins, you don't want to cover all your bases, no whole food supplement like vitamin or a plant-based supplement that you could take during the day. No, none of that. I subscribe to the idea that a lot of it's expensive urine. And I'm testing myself, so I know if I'm deficient in something bad, all my vitals are close to optimal. So if something's out of whack, I'll see it probably.

So you were saying you do things for the government. What do you do? Did I say that? Yeah, you said that earlier. You said I should ask you. Oh, no, I didn't. Yeah, you did. No, I didn't.

Before the show started. I was outside. I was feeling frisky. Now that I've thought about it, I want to go to jail. I'll talk about it. I don't want to get you in trouble, so let's pause and think this for a moment. Are there things that you can't talk about? Please don't want to get you in trouble, so let's pause and think this for a moment. Are there things that you can't talk about? Please don't. There's a lot to talk about.

I just have to make sure it's nothing that's confidential. But there's a lot of interesting stuff going on on the planet. There's areas of biodefense that are pretty scary. Some nations are apparently working on using CRISPR and other gene editing systems and modifying bugs that could wipe out a few hundred million people pretty quickly. What do you do? How do you detect that? Even the flu, that's a massive bio threat and it may just be natural. And that could wipe out another hundred million people like it did exactly a century ago. exactly a century ago. So I work on that stuff, detecting viruses, wiping them out,

cleaning a room of DNA, making sure that everything's clean. So I'll give you an example. So the Navy SEALs came up to my lab and they'd like to ask our group to solve some hard problems. And so the problem they set us on was, how do you kill anthrax safely? Now, right now, it's very difficult to kill, of course. When the anthrax letter was opened in the Senate, what was it, a number of years ago, it cost $25 million. They had to seal it off and put hydrogen peroxide all over everything, destroy the computers. So they're wondering, how do you kill anthrax safely so that you don't have to be in a hazmat suit to do it? And so what we came up with after thinking about it for about a week was we need a biological solution, not a chemical. And so we found an organism that it's whereabouts I cannot disclose, but it's a very interesting organism that grows at high temperature.

And it destroys all bacterial and viral life. And it wipes it out, and it doesn't hurt humans at all. Or at least in animal studies, you can breathe it in, you can put it anywhere, and it's fine. So this is a cocktail of enzymes that destroys the microbes, including anthrax. So it doesn't have any effect on humans, but what about the bacteria that lives in our body? enzymes that destroys the microbes, including anthrax. So it doesn't have any effect on humans, but what about the bacteria that lives in our body? Well, we haven't eaten it yet. What we're hoping to do is to do a clinical trial soon on removing biofilms. So in the wounds of patients, the problem, the reason they don't heal very well, especially these diabetic chronic wounds, that by by the way, every 10 minutes someone's losing a limb thanks to that. These biofilms, you have to digest them off. And do you know how they do it right now?

They scrub them off. It's horrific. And then they cut the skin. And they keep cutting and they're cutting and eventually you lose a limb. This looks really promising in animal studies that we should be able to not just kill the bacteria in the wound, which is a problem, but get rid of that biofilm. That's amazing. So things like MRSA, staph infections.

Exactly. You'll be able to stop it in its tracks before it gets systemic. Right. Spray this stuff on a cruise line for the virus, norovirus. If it turns out to be that safe, why not just wipe down schools? Because I always worry about the negative aspect. Like what's going to happen? Like what's going to be the blowback, right?

Like antibiotics is what's created medicine-resistant antibiotic staph infections, right? Right, right. Your mind always jumps to the worst possible scenario. That's me, bro. Love it. We'd make a good team. So I'm the optimist. Like a buddy cop movie?

Yeah, let's do it. So we've tested, does it induce antibiotic resistance? And so far, it's negative. Okay, interesting. Oh, another thing I'll tell you. So I work with a company that detects organisms. So we want to detect if there's another virus coming across the planet. So how do you do that quickly? And how do you do it if you don't know what you're looking for? So we can take a drop of blood or a swab off a table and we can see all

the organisms that are there. We can do your microbiome, but that's easy. So a drop of blood will tell you all the bacteria and viruses in there and it'll tell you how to kill it, which is great for healthcare because right now, microbiology labs, I've worked in one. I used to swab urine and poop on plates. It was very glamorous. That's how it's still done. That is, that's 19th century, early 20th century technology. Grow it on a plate, wait a few days, see what grows. But that's useless for diseases like viruses and Lyme disease. Lyme disease, you know, the one from ticks in your spine. My daughter got Lyme disease and she was really sick. She was losing her eyesight.

It was serious. It got into her brain. And the hospital wouldn't give her the antibiotic because the tests weren't quick enough. And they wouldn't give her the antibiotic until the tests were positive for insurance reasons. And I said, just give me the DNA of my daughter, the spinal fluid.

I'll test it. They wouldn't do that. So I was furious. So I spun out a company out of my lab with some very smart bioinformaticians, mathematicians, software engineers. We built supercomputers to be able to do this. Teamed up with a guy in Stanford, my friend, I mentioned him, Carlos Bustamante. He's the guy that did, or maybe I shouldn't, but he did a famous person's genome recently. He's been trained on mummies and he did Kennewick Man.

So this technology can be teamed up with what I've done to be able to get rid of all the human DNA out of a blood sample, leave the viruses, leave the bacteria, and then run that through a supercomputer, all the DNA, and tell you within probably seconds eventually what it is. So my daughter would have a diagnosis within eventually it'll be just 10 minutes instead of waiting a week. Wow. Lyme disease is terrifying. There are so many people that are infected with it.

And I know personally maybe 10 people that have it and a couple that have had significant issues with it that have lasted for years. I know a guy who was hospitalized for a full year on it. It's really bad, and it can hide as well. That's the problem. Yeah. And it wrecks joints. And a lot of countries actually deny that they have Lyme disease. Australia's a good example.

People are getting what seems to be Lyme disease disease and no one knows if it is or not. Give those samples to us. We'll tell you what's in there. Well, it seems to be very difficult with certain doctors for them to tell if they don't see that bullseye infection. Exactly. So my daughter, our daughter, Natalie, our middle daughter, she didn't have a bullseye. She had nothing.

The first thing we knew- Explain the bullseye. oh so it's um inflammation around the bite of the tick right and um and there's a there's the actual bite and then there's a circle on the outside of it and for whatever reason this occurs with lyme disease but oftentimes goes away quickly so if you bring a person in and they have the lyme disease but they don't have that bullseye anymore which is what happened to my friend steve's son he tried to tell and they have the Lyme disease but they don't have that bullseye anymore, which is what happened to my friend Steve's son, he tried to tell them that it was Lyme disease. The doctors were incredulous.

They didn't believe him. It took until the kid had Bell's palsy in his face. Exactly. That's what happened in our family. It's crazy. And so I was bitten by a tick last year right behind the knee, and it didn't form a bullseye. Maybe I didn't give it time, but it definitely was a very painful thing. I could tell that there was something going on.

It was really itchy. And I went to the pharmacy and I said, can I have the antibiotic? It probably costs a few dollars for the antibiotic. And they said, no, we won't give it to you until we see a bullseye, and you need to bring the tick in well i didn't bring the tick with me so again i'm the doctor's and nurse's worst nightmare i wouldn't leave until they gave me the antibiotic and i'm glad because i don't want to wait did they eventually give it to you they did i wasn't going to leave until i got it

uh but i don't want to wait a week you know i'm starting to lose my did you get upset with them you say listen you dumb motherfuckers i'm super smart i work with genes uh no not that occasion it's tempting it's tempting you know you can always say hey i'm a professor at harvard and then they probably just really kick you out yeah what do you say i mean how long did it take before they listened to you? So I went through it. Basically, I started spouting biology so that they knew that I knew something about it. It was about 15 minutes. Oh, that's not bad. Thank God you knew what to say. I did.

I'd be there for days. Like, bro, trust me. Right. Let me draw you a picture of the tick. Yeah. I mean, I would just think they'd want to hand that stuff out quick with so many people getting it. It's so common. I mean, we looked at a map recently on the podcast of Lyme disease infections across the East Coast.

And the East Coast of the United States, obviously that's where you live, is just a hotbed. It's crazy. It's everywhere. Well, it is. And I've got friends on Cape Cod where it's really prevalent. Really bad. So bad. So they keep the antibiotic in their kitchen drawer. Jesus.

And if you catch it quick enough, does it stop it in its tracks? Yeah. So the real problem is when it gets into your bloodstream and you don't treat it long enough or quick enough. Exactly. And so my daughter needed what's called a PICC line, which is delivery of the antibody straight into the heart. Oh, God.

Because they left it too long. God, I want to kill them. And she didn't have a ring of inflammation. But you knew. I didn't. I thought it was meningitis bacteria in the brain or something. Oh, God. Or leukemia was the other possibility.

Those dirty fucking bugs. What can be done to somehow or another eradicate those things? Oh, so, um, again, one of, one of my friends got a few friends here.

Uh, she was working at MIT and she's developed a way using the CRISPR system to kill these, as you say, damn little fuckers. and so there is possibly going to be the first test of releasing a modified organism, the Lyme organism to kill them off. Wow. You know that's going to cause some new superbug.

It's going to kill everybody. It's going to be like that Brad Pitt movie, the zombie one, World War Z. Might be. But on the other hand, we might all be saved from Lyme disease. Yeah, I would like that. That would be great. I mean, where did Lyme disease come from? There was some conspiracy theory website that was thinking that Lyme disease was some sort of a biological weapon. That's probably bullshit.

I'm sure. But it came out, it was in Lyme, Connecticut, right? Wasn't that one of the first cases? Yeah. So that's close enough to harvard stayed away i thought you said russians were behind it oh no i said conspiracy theory i didn't say it was russian but it was a biological weapon it's uh it's just an awful thing and that and now there's the i'm sure you're aware of the Lone Star tick that gives people that alpha gal disease, the one that makes you allergic to red meat.

I mean, where was that before? It's crazy to see these things morphing. Well, they're morphing, and there are a lot of bugs we don't know. Somebody just published a few days ago that they took surveys of the microbiome on the skin, mouth, gut, across the planet, different races, different foods, geography. And they have 100,000 different organisms living on humanity. And most of them are unknown. That's crazy, right? Right. And all they have to do is just morph a little bit one way or the other way, and all of a sudden, people are dropping like flies.

Yeah, and what's interesting is on the skin and in the gut of people in India is very different than what we have. And the different smells. They probably think we smell bad. But I know this because some of the- Well, they're wrong. Yeah, right. I smell like Old Spice.

But these wounds wounds they're actually if you want to kill the bacteria in a wound they're different in the wounds of people in India than they are over here in the US

oh wow that's interesting and obviously they have different diets too so there's probably different things they're used to consuming and so their gut bacteria

is different right everything's different their genomes are different so we need to map the globe to first know what we're dealing with before we can address it. It just seems like a never-ending struggle. Every day is a struggle against the natural world. They want to kill us and eat us.

Yeah. Everything. The little things and the big things. All of it. Wow. We're food. So how much of your time gets consumed with this kind of work uh well it's all everything's all consuming my typical day is uh i've had to go into a company meeting going to the u.s government um became called by senator for an update uh so probably uh actually let me be formal about this Harvard University allows me to spend 20% of my time outside of the university so it's 19.9

hmm do you have to cover your ass here is that what you just did? maybe but who tracks their time now anymore? but I would think that with a guy like you who's so you concentrate so much you're you concentrate so

much you're so focused on anti anti-aging that having a gigantic workload would seem to me to be that would be an issue in terms of like overtaxing your system stressing yourself out so nobody's ever asked me that and it's a really good question. But I'm not really worried about dying. Actually, I'm not worried at all. At all? So there's a wolf in the room, he's staring at you, you're not worried about dying? That'd be a grisly death. I'd probably not want that, but I've been I thought I was going to die on airplanes before, and I'm pretty calm about that.

So I guess that's a good test. But I do want to leave a legacy. I want to be able to say the world's better for me being on the planet. And so that's why I do all this stuff. I try to protect the humanity. I try to protect nature. I'm trying to help with food production. My aging stuff is what I'm known for, but i do a lot of this other stuff um that

people don't know about so you your concern is anti-aging you certainly want people to live longer but you yourself are more concerned with your work than you are with your own personal life oh a hundred percent my wife will tell you that. The reason that I look after myself as best I can when I've got the energy is it would be a bad look if I died from heart disease tomorrow. Yes. The anti-aging guy. Well, if you died from anything other than an accident. Right. So I'm trying to be a role model for others. But if I died tomorrow, that would be fine with me. I'd like to finish my work at least. I would like to leave something behind.

But what I don't want to do is to be a burden on my kids and my grandkids. And so that's what I'm also trying to prevent. Yeah, that would seem to me to be the real final frontier of anti-aging is folks that are really, really old, because it seems like they would be open to try almost anything. And if you could bring them back, that would be uber bizarre. Right. How far away do you think we are from doing something like that? Well, it often comes as a shock to people who don't work on this that we're already testing these molecules in clinical trials on elderly people. I've been doing that for a number of years now with some positive results. Over at Harvard, we were giving NMN and another molecule

called MIB626. What's the other one called? My laundry list. So the company's called Metro Biotech, and it makes super NAD boosters. And the drug is called, developmental drug, is MIB-626. 626. Yeah. And we're hoping that it will not just rejuvenate them. Is that an alleyway somewhere? Ah, yeah. I got to go to some shady doctor with a weird accent.

I got to go to some shady doctor with a weird accent. That one we hope to get on the market in about three years from now. Really? Yeah, for diseases, FDA approved. And so they're using it right now on old folks? Testing it for safety, yeah. But we're also going to be testing later energy. We can measure actually the NAD levels, that molecule I just mentioned.

We can measure that in their muscles, and we'll test if that worked. And we'll measure, of course, their endurance. Because the mice that we treated with NMN, they just ran and ran and ran. They actually broke the little treadmill in my lab because they ran so far. And you're giving it to them orally, or you're injecting it to them? It's a little tablet. They just put food, put it in their food or something like that? Oh, the mice? Yeah. Oh, no. I thought you were talking about the humans. In the mice, we put in their drinking water. And they just drink it. It's really easy.

Wow. And they have no idea? No idea. And in fact, the people who are running the treadmill have no idea which is which. But we had mice running three kilometers, and then the machine stopped. And I get a text from the researcher, hey, the machine broke. And I said, check the software. It turns out the software was written to stop at three kilometers because no mouse had run that far before. That's long. And those are old mice. Don't forget, these are mice that are the equivalent of a 65-year-old human.

Really? Yeah. And we figured out why they run further this isn't just uh try it and see we figured out that that the lining of the blood vessels needs nad as you get older well they need it all the time but as you get older you don't have enough nad so the nmn replenishes that and allows the blood vessel lining to respond to exercise and even grow blood vessels if you don't exercise. And so those mice, they ran and ran and ran.

They didn't get lactate buildup as much. They just didn't feel tired. So they didn't have lactic acid buildup. Right. Wow. So muscle fatigue would be different. Well, they didn't seem to get that either. Wow.

It was just better blood flow. We even pinched off an artery, and the body responded much better to restoring blood flow, which would be great for patients who have a heart attack. Whoa. Now, with human beings, what has been the most dramatic result? That's a hard question because a lot of it's early stage. We developed a molecule that seemed to effectively treat a disease called psoriasis, which is the inflammation. Yeah, Fentanyl has that. Yeah, so that worked.

And that's a molecule that's- Is it something you apply to the skin? It was a pill, actually. Yeah. And how does that work what is it doing uh so it's an activator of one of these sirtuins that we found in yeast originally these are two unprotective enzymes in the body and they're anti-inflammatory and so it worked well against that disease so psoriasis has something to do with inflammation it is an inflammatory disorder yep um are all autoimmune disorders anti or inflammatory based disorders i believe so really interesting hmm because i have uh i have vitiligo you don't see the little spots on my

skin where i don't have uh any pigment it's genetic my grandmother had it my grandmother's sister had it um i wonder if that would help me uh yeah i really couldn't say what's it called again which one the drug that was tested yeah um it has a name srt 2104 and this is the stuff that worked on psoriasis yeah in, in a small study in New York, yeah. Now, what other things had really dramatic results on humans? Well, we're not there yet. We don't have dramatic results on humans yet. Is there anything promising results on humans other than NMN? Yes, there are. So this mTOR I mentioned earlier where the drug rapamycin,

which is too dangerous to try on normal people, that drug has been tried on elderly people and it boosted their immune system in the same way that you see with calorie-restricted mice. And so that was an early signal that you might be able to reverse aspects of aging in the elderly with that drug. drug. Now with older folks, one thing you see is the body doesn't produce collagen as much, your skin gets lax and starts to sag. What things could be done to mitigate that? You mean besides Botox and stuff? Well, Botox doesn't really do that. It just freezes your face like a word. It does. Well, so I'm asked that a lot. David, don't worry about protecting cancer, heart disease, Alzheimer's. How do I look better?

Can I look better? Yeah, right. And the answer is that, A, we don't know. B, we're working on it. We work with a cosmetic company that so far is so good. But I don't endorse products. That's not me. But also what's interesting is that these mice, at least, they stay younger looking as well.

They don't just live longer. So there's hope that, I mean, the skin is a big organ. Okay, so why wouldn't it stay young just like the rest of the body? Well, it's certainly indicative of whether or not a person's healthy, right? If you see someone and their skin is really saggy and fucked up looking, you assume that person's not healthy. Right. And actually, a lot of us scientists believe that how you look is actually a pretty good indicator of your biological age. Speaking of biological age, there's been a breakthrough the last few years being able to tell your biological age. One part's done by

inside tracker looking at blood biomarkers but there's a new one called the dna clock have you heard about this yes i have so a colleague of mine um is well known for it steve horvath and what it is is so you know how dna i said is changing over time and the epigenome is changing so these are like scratches on the clock on the dvd we think we know what those scratches are and how to remove them and what they are little chemicals that bind to the dna called methyls and the older you get the more methyls you accumulate on your dna and we can read that with a machine. And we can very precisely say you're roughly this age, but you're actually older or younger for your chronological age. And now we think we can reverse that.

Wow. How long do you think you are away from doing that, being able to reverse that? Well, that's that glaucoma treatment that we're looking at. I'm going to reverse that. Well, that's that glaucoma treatment that we're looking at. I would like to see you take someone, like a wealthy Mel Gibson type character, and just shoot them up with everything. Like, just get someone who's willing to give you a full run of them, like some sort of a science fiction movie. Tell you what, I'll do it. If you'll employ me, because I'll be kicked out of my job if i do it i'm sure you would but man i mean it just seems like there's so many promising

things it would be really fascinating if you could document that you could take one person it was like a wealthy man in his mid to late 60s yeah well there's this fringe element in anti-aging in fact i don't even like the term anti-aging. What do you like? Longevity research. We're about to announce, maybe this is a sneak preview for everybody, an academy for aging research of the top, I think, 20 scientists in the world are banding together to produce white papers and opinions.

But yeah, we call it longevity research. So anti-aging is more the Botox and that kind of stuff that we don't want anything to do with. Right, but that's nonsense. It's not really anti-aging. You're not doing anything about aging. You're just freezing your skin so it doesn't move. That to me is one of the weirder things,

especially with men. When I see a man and his forehead doesn't move, I want to smack him in the mouth like what's wrong with you sir how dare you smack it's just it's not it's a it's not like botox or fillers or any of those things you're not doing anything for your health or your actual real vitality you're just weirdly doing something cosmetic right yes you are um and though i think their defense is you feel better if you look better and psychologically it might help i don't think they look better though they just look different yeah that's the problem it is true um yeah i don't spend a lot of time thinking about the cosmetic industry for obvious reasons. I'm trying to save humanity and improve the planet. Actually, I do think we would be judged as a species if an alien came down and they said – You're shooting botulism in your face? The fuck is wrong with you?

Right, right. Exactly. You are a weird – you're not allowed in the club of advanced species. Well, that would only be one thing that we're weird from. Yeah. But what would they ask you? Well, they'd ask us, have you figured out the speed of light? They'd ask me why I have drawings all over my arm. No, they might appreciate art. Maybe.

But they'd be like, why didn't you just get it and then just wash it off or something? Why do you have to get it drilled in your skin well that's coming but i think what are that one of the most important questions they'd ask to tell if we are an advanced nation or advanced species is have you figured out aging yet right deterioration yeah and you know what we're so pathetic as a species our answer would be you mean that's a thing? You can do something about that? And they're like, come back in a thousand years. Well, I mean, there's got to be. How many people do you think worldwide are working in your field?

So in terms of leading labs, there's about 20, 30. Broadly, there's probably a few hundred labs. And are they all in essentially the same field of study? They're all working with the same field of study? They're all working with the same molecules and the same parameters? No, not everyone works with molecules. But what I can tell you is we get together in conferences and we talk about discovering a new gene that extends lifespan and a new molecule that's working in mice or sometimes in humans.

But it's a big field now. It's grown. And when I started, it was the backwater of biology, antioxidants, et cetera. I was very lucky to start when it was really small and stick it out. There was a fair amount of criticism in those days. How so?

Like, a lot of my friends, my supervisor said I was insane for working on aging. That's not a thing. That's not biology. Really? Yeah. Wow. Wait, how long ago was this? So I came to the US from Sydney in 1995, went to MIT. And the scientists in the lab that I joined,

Lenny Guarente's lab, two students had just started working to figure out why yeast get old. And I joined as the third senior person to join. And all the other people in the lab, there were about 18, 19 people, they said, you are nuts. Lenny's lost his mind. He's working on aging. That's not a thing. You should be working on what we do, which is understanding how genes are regulated. So I called up my mom and I said, I think I've made a big mistake here. I thought this was the thing and the guy and everyone here says he's nuts. Meanwhile, you were right. Well, you got to take some risks in life. That's one lesson.

Yeah, but that's an interesting one, right? Because you were a young fellow. You didn't really totally know. It was pretty lucky because I'm in Australia, right? I don't know what people are saying about this lab until I get there. But I've always been fascinated with aging since I was four. Well, now though, with all the promising new discoveries, I mean, they have to be eating crow as it were. You ever talk to those people? They go, Hey, fuckface. I was right. You don't call them up in the middle of the night?

Drunk? No, I definitely forgive people too much. fuck face i was right no you don't call them up in the middle of the night drunk no i definitely forgive people too much i've got had some pretty big enemies along the way but i try to be nice is it because uh research and this sort of scientific work is so competitive yeah it is it is and there's this belief that someone's success is your failure it's not really that that is the case but that exists in show business too. It's a weird sort of mindset. It's a very limiting mindset. And this may be true in Hollywood. In science, if you come up with a new idea and you're young, you're a young Turk, and you're upsetting the status quo.

Thomas Kuhn's book on the structure of scientific revolutions just had it right. He wrote in the 60s about chemistry and physics, but it applies to biology. If you come up with a new theory that's that disruptive, the current leaders will attack you, and it's a period of chaos, and you just have to get through it. And fortunately, I'd read Kuhn's book, and I knew that this was normal. But a lot of people around me were saying,

oh, no, people are saying we're wrong, and it's controversial. We don't want to be controversial. I'm like, controversy is great. Let's do more of that. And if it's not controversial, I don't want to do it. That is interesting. Do you think that's because the people who are the old guard are upset they didn't find it themselves or are they upset that your new findings will make their work look irrelevant? Yes, it's probably a bit of both, but mostly it's that they're worried that their lives will have been in vain if what they're working on is not true. Right.

Yeah, there's an amazing documentary on the Sphinx where these geologists are talking about some of the water erosion outside the area of the Sphinx, and they're saying this points to the fact that construction was thousands of years older than they thought. And you see this one Egyptologist freaking out. He's freaking out, like, what evidence? What evidence of this culture are you talking about?

Because apparently it would have predated the known dates of 2500 BC, would have made it like 7,000 years older than that because it would have to be back when there was rainfall in the Nile Valley. And you could see this guy's ego kicking in because he was a professor, he had been teaching Egyptology, and he was freaking out. Instead of examining this evidence like, whoa, like talking to this geologist who studies rocks and erosion, who's really steadfast, He's a Boston University geologist, Dr. Robert Schock. And he's saying this is evidence of water erosion.

And he's showing it, and he even showed it to a bunch of other geologists, and they all agreed. And this guy, this Egyptologist in this documentary was freaking out. I was like, wow, that's what happens when you think your whole life's work is horseshit. Yeah, it can be a blow to the ego. I haven't lived through that yet. It's probably coming. But what I've noticed is that the really successful scientists and people in life just embrace change and go with it.

Yeah, kind of have to. I mean, it doesn't mean that that guy is a loser. It just means he was acting on incorrect information based on what they knew before. I mean, you should embrace it and say, look, well, we know certain things were built at 2500 BC, like the Great Pyramid. That's been pretty clearly established. But it looks like there were some ancient structures that were there even before then. Now we have new things to study.

They don't look at it that way, though. Yeah. See, the problem with how biology and actually most facts are taught or theories are taught is that there's a textbook and that's the Bible equivalent. What I try to teach my students is can you please just forget everything you've just learned? And what's important to know is that most things we think we know are not correct. They're going to change over time. All theories change. Newton was wrong, but he helped us get here.

Change over time. All theories change. Newton was wrong, but he helped us get here. Expect that we only know 0.01% of what we need to figure out, and a lot of what we think we know is wrong anyway. So even if you have the greatest theory, expect that it will be overturned. But you can at least cherish the fact that you've helped us get to that point, because without Newton, we wouldn't have quantum physics. Well, for me hearing you say that it's very promising and it's it's it's very encouraging but i always thought that scientists were always going on just data like the all they cared about was data all they cared about is what is correct and that was what was crucial that's what's important

this is what they talk about this is what they study when i found out that scientists would would ignore information or use their own personal biases against information or attack research because it somehow negates what they've done it's very disheartening for someone who's not a scientist you go oh no the ego is in science too right it's disheartening for someone who's not a scientist you go oh no the ego is in science too right it's disheartening as a scientist i can tell you there was a time of great change in the aging field where we discovered genes control aging and molecules like resveratrol could extend health and lifespan it was it was brutal you i'd get up and i'd give a speech and someone would say you're wrong this is crap and are they now? Do you call them up in the middle of the night?

Call them up, you dumb motherfucker, have a couple of glasses of wine Yeah, well I think the secret to success in life is actually just existing for long enough and all your enemies just fall away Yeah, well they die, they're not into anti-aging They all look like shit and they can't walk anymore. Just have to outlive your enemies. It's an easy way. That must have been a tough time, though, for you as a young man. And you're hearing this from these established scientists and part of you must have been thinking, like, geez, are they

right? Sure. You have to entertain the possibility that you're wrong. That's what we do. But you go back to the possibility that you're wrong, that that's what we do. But you go back to the lab and you retest it. So I went through a really brutal period in my career where we had data, we interpreted it, we published it in the top journals, and it was about how resveratrol works on that sirtuin enzyme that I mentioned. And Pfizer came out with a paper that said, it's all wrong. And I had people call me up saying, you know, it was nice knowing you. I'm really sad for you. It's over.

Yeah, bad luck. And so I went back to the lab. We had some data already from years before, which I knew were interesting. And it took another, I think, four years to get to the bottom of it. But it turns out in the end I was right. But there were days when I said, screw humanity. I can't even be bothered getting out of bed if this is how I'm going to be treated for trying to devote my life to the betterment of people's lives. It's tough. I think anybody who's in a position in their career like that has to have gone through really hard times.

It's just discouraging from a non-scientist who relies on people like you. For someone like me, who relies on the folks like you out there doing the hard work, that you would face that sort of, I mean, I guess the best way to describe it would be ignorance. Well, it's okay for scientists to challenge a theory. That's what I did and what everybody is trained to do. But to do it in such a public and controversial, it was vicious. It was definitely vicious. Even the words they used were vicious, which is really hurtful. But they're wrong. Well, they might have been right.

But they were wrong. Call them up, middle of the night, you dumb motherfucker. Yeah, the person who published that paper, I do think about meeting that person again. But it can destroy careers. It's not just it's tough. You can run out of money. Your students go away. That was happening to my life. We went down to four people.

And what was the high? I mean, these days, before then then it was about 18 20 and you went down to four four so it was looking bad oh yeah people had written me off holy shit but you were right well you got to push forward it's uh you got to get lean because you're not going to get government funding for a while because people think that you you're a failure god damn that's crazy well science is not for the faint of heart i would imagine yeah yeah boy skin thick skin uh stubbornness uh only only those survive right what was uh the turnaround like was there a moment where it turned around and

moved into your favor yeah there was there was. There was one day when it all changed. So the earlier data, so we're data-driven. The early data was that the enzyme, we could mutate or change the enzyme so that it wasn't going to be activated by resveratrol, and we found that mutation. Now that just technically or non-technically means that we could change the enzyme in a way that wouldn't work. So we then put that non-working enzyme into a cell.

And now we have a mouse that doesn't work. And we give it resveratrol. And if it works, it means I'm wrong. If it doesn't work and it's blocked by that change in the enzyme, we're probably right. And that's what we did. But the real change was that there was a company that I started that was making drugs, the one that cured, or at least seemed to cure psoriasis. And they had made these very synthetic molecules that were not related to the plant molecule resveratrol. And so I said to myself and to the student who was working on it,

the very brave student, if the change in that enzyme also blocks the drug, then we're onto something. Because that means two separate groups working on separate types of molecules, different people, different systems, all get blocked by this one little change in the enzyme, then we're right. And so he walked over to the company, got the molecule, threw it on the enzyme, and it didn't work on the mutant. And that was me rejoicing because I could say there is a universal activation mechanism on this one enzyme.

Resveratrol works. The molecules at the company work. And now there's an interesting thing that just came out from Spain that metformin, the diabetes drug, may actually work the same way as these other molecules by activating our favorite enzyme, the sirtuin. Wow. And how much time were you in the dark lands? It was a couple of years of hell. A couple of years.

Right. It gets so bad because you've got this tight-knit group of scientists, and you have lab meetings, and you present your results, and usually you're very supportive, trying to help. I had one guy saying to my student, David doesn't know what he's talking about. You shouldn't work on this. It's been proven wrong.

He was dead against me in my own lab. I'm paying his salary. And it's okay to be constructive constructive but vicious within my own group well suffice to say he wasn't in my group for that long wow now this other guy that used all these other vicious words about you where is he at now not sure i would know i would know no i don't have time uh to look. I'm looking forward. You're nicer than me. Yeah, you know what? In science, because it's very collaborative, and often your enemies are reviewing your own work,

if you build up too many enemies, you won't survive. No, it's definitely a healthier approach. I'm kidding. I probably would do exactly what you did. But still, it's got to be beautiful to come out on the other end and be proven correct and actually be at the forefront of these emerging technologies. Well, it is. I mean, I don't rest on any laurels. But what I do is I pause and I remember how hard it was to get here and how fortunate I am to have made it this far.

was to get here and how fortunate I am to have made it this far. And I'm working with hundreds of collaborators around the world to make this come true, this idea that we can really treat aging and prevent deterioration. So I'm blessed. I have an app on my phone that I've helped engineer. What's that? It's called Lua, L-U-A. What is that?

Well, it's a little company that we bought in New York and nurses and dentists use it to pass medical information around, but we use it to share information between scientists around the world and coordinate activities between companies that I've started. Yeah. So, you know, I think I mentioned to you that I've started a few companies. What I'm trying to build are companies that are the 21st century version of a pharma company that actually has a decent reputation in the world. I think it's pharmaceutical companies,

whether it's deserved or not, have a pretty bad rap. I'm trying not to fall into that trap, but I'm also trying to use 21st century technology to not become too bureaucratic as well within the organization. That's what the Lua app offers us. You were also talking – I don't know if you could talk about this – before the podcast about how you have to make sure you have zero conflicts of interest. Yeah, it's hard.

So I don't sell any supplements. I don't endorse anything, no products. But if you look on the internet, if you Google David Sinclair and NAD or aging, you'll see that people put my name and my face all the time on their websites. And I get questions every day. Every morning I wake up, which product are you endorsing? And so I have to be extremely careful. So do you have to have a lawyer contact those companies and tell them to take your name down? I do. Yeah. Yeah. extremely careful so do you have to have a lawyer contact those companies tell me to take your name down yeah yeah so it's a fair amount of money always sending out cease and desist letters but i have to do it my reputation is everything and i also want to be able to have opinions on

these molecules without someone accusing me of doing it for a profit that's what i would think would be correct because if anybody could point to that and say, hey, he endorses this because he's making money. Yeah. Yeah. That's what would be – yeah, that would be the thing that – I mean, especially because most people aren't going to do real research and develop a nuanced understanding of your work and what you're doing and what it means and how long you've been studying it. They go, oh, he's doing it because he's making money. I'm done. Right.

Well, I've made a fair amount of money in my life. My first company, even though I wasn't the major shareholder, was sold for north of $720 million. So money I'm not immune to, but I do reinvest almost all of it. Actually, all of it, my wife will tell you, into new ventures to change the world. So the Lyme disease company and the MIB626 company, Metro, these are funded initially by me. Now, the conflict arises because I'm studying these molecules in the lab and I'm on the board of directors and advising these companies

as chairman, vice chairman. The only way around that as a scientist that we have as our defense is we disclose everything. So initially, I would disclose it to the government and to Harvard. All scientists have to do that. But I've gone a step further just to try and be ultra-transparent with the public. And so I have a website.

If you go to my lab's website, you'll see everything that I do and hopefully that's protection from being accused of being biased. But what I definitely do in my lab is I say to the students, if you get a whiff that I'm doing anything biased, I wouldn't do anything consciously, but maybe there's some unconscious bias. Let me know. Let the university know and we'll be fine. But I've been doing this for 25 years. I think I'm pretty good at putting a wall between the two. And the other

thing that I want everybody to know is in the lab, we do very basic research. We try to understand the fundamental reasons why we age and how to reverse it. The companies are more worried about how we're going to do a clinical trial, which is a very different world. So they don't overlap much. Now, when you want to bring something to try or something to the market or you want to try something on people what's the process like say if you have some sort of a molecule that you want to try out on people what is that process so it's a few years of often making a better molecule but let's say you've done that work. Now you spend a year testing it on at least two different species, usually a rodent, a mouse, and a dog. But you try to do

everything you can before that to make sure it's not going to be unsafe, testing it on cells and other things that are not living, or at least don't feel anything. But the FDA, Food and Drug Administration of the US, requires if you're going to make a drug, you have to test it on at least two different species. So that's what you do. And then you go into what's called Phase 1, which is safety testing.

It takes one to two years. Phase 2 is what we call efficacy, which is does it really work potentially? So you test that on 50 to 100 people. Maybe it works, maybe it doesn't most things fail if it looks good then you go into phase three which is 50 to 200 million dollars worth of experiments um testing it on hundreds of patients and if that goes well then you apply to the fda to be licensed uh to sell a drug so the amount of money that it must cost to bring something to a market, you just open your mouth like, oh.

It's hard. It must be staggering. It's staggering to raise that much money, and that's one of the reasons that these big numbers come up. Often we have to tap the public markets to be able to afford it. A typical drug will cost hundreds of millions of dollars. Some drugs have failed after $700 million investment. But look at the upside. If we're successful at having a drug that treats aging, we'll treat a disease like diabetes first, but then it could become the best-selling drug of all time if it's proven safe. Who wouldn't want to have a drug that could protect them from all these major diseases?

Yeah, but how much would something like – you'd have to sell it for so much money to make up for all the research money, right? Is that how it works? That's how it usually works. But for the first time, I'm in control of many of these companies, and I have a large say in them, at least. And I, as an individual, am pledging that we won't do that. We're not going to put our prices up to what the market can bear. We want – this is a gift to the world. And so that's a very different approach, and that's one of the reasons that I've, in large part, used my own money to do these things so i can have that say and do

what's right for the planet so when you do do that um how will you decide how much something costs based on the ability to just maintain the company well yeah we have to be profitable otherwise it all goes away right um but not to the point of extortion no there's there's a nice meal ground what right you don't want to be like that guy that went to jail for the AIDS drug. What's that asshole's name? You know that kid? You know who it is. Oh, Squirrelly.

Yeah, that guy. Martin Squirrelly. No, I have a very different view, and I'm hoping that we'll have a new type of pharmaceutical company emerging out of what we're doing. That's amazing, right? Because pharmaceutical drug companies are always thought of as being a devil. Meanwhile, they're responsible for so many things to keep people alive as well. But because of the fact they're connected to things like OxyContin and fentanyl and things that kill people,

and it's been proven that there are certain unscrupulous drug companies that have pushed things out there that they know have negative effects because they knew they could profit from it. Right. Well, not everybody's ethical but as long as i have a say in these companies they will be ultra ethical you got to make sure that you stay alive they're going to try to take you out bro well yeah uh i don't know about that but take you out and take control of the company i've found profits i found like-minded investors for the first time. That's amazing too. I mean, how have you managed to cultivate that? Relationships.

It's harder than going with a pitch to a capitalist, but it's mainly meeting the right people. I want to see that they're on board too. I don't want to just have somebody who's out to make a profit. Right, but you still can make a profit. Still be profitable, but don't go crazy. Right. Right.

Help the world. Yeah, and so we just recruited to one of the boards of the company someone from a consumer company, which is a strange choice, right? But this is a person who's done right at that company for the world, a company that used to make just some consumer products that weren't healthy. And he turned that around. And that's the kind of person I want to work with who cares about the planet more than they care about the ultimate profit. But that's awesome, man. Listen, keep me in the loop. I want to know what's going on. And I'm going to try all these things that you said. So I'm going to go out, I'm going to buy to buy some nmn i'm going to buy some resveratrol um i gotta find a quack that's willing to prescribe me metformin i gotta you know any shade we'll talk later um and then the other stuff the srt

2104 that stuff where would one get that that's experimental that's probably where would one get that? That's experimental. That's probably the hardest one to help you with. You need to pay somebody off. Anything else I need to know about? Is that it? Have you had your genome done? Just 23andMe, basically. Is there more extensive versions of it than that? There are.

I mean, they're a few thousand bucks to your whole genome. We could do that, but I don't think you'll learn a lot more, mainly because we're ignorant as to what the other stuff's doing. Right. It was pretty interesting, though, as far as finding out about my ancestry and where my relatives come from. Yeah, it's a good start. I learned some really interesting things, too, about my origins,

and I'm carrying cystic fibrosis gene and whatever. Oh, wow. But what's cool is now we're merging. You can merge that data with the inside tracker data and have this ultimate personal angel for health that will hopefully one day be on all of us. We've got a personal tracking device. It'll tell us if there's something going wrong. If you've got a cancer cell detected, go get that eliminated. It's crazy these days. We have to wait until there's actually a tumor that's making you sick before you actually

go to the doctor. An actual issue. Well, now I know why you're so excited about the future. You have an inside track on this. Yeah, front row seat. I'm glad to have shared a little bit with your listeners. Oh, thank you. I really I really really appreciate it tell the listeners and the viewers what your website is I just have a

Harvard website but I will be I'll tweet about this I'm launching a website for a book that I plan that I'm writing now and it's going to

come out later this year we hope when it comes out come on back would love to give you an update thank you David really really appreciate it

that's it bye everybody Come on back. Would love to. Give you an update. Thank you, David. Really, really appreciate it. That's it. Bye, everybody. Bye, everybody. That was great.