HARVARD SCIENTIST REVEALS The Surprising Secrets To AGE IN REVERSE | David Sinclair & Lewis Howes

There's a clock in the body that we can measure. We can predict how long you're going to live based on that clock. And what we found is we have a new gene therapy, but hopefully one day it could be a pill that resets the clock and cells go back to acting and being young again.

I think you got to have a dream. The School of Greatness. Really? Yeah. Please welcome Lewis Howes. Welcome back, everyone, to the School of Greatness podcast. I'm super excited because my guest today is David Sinclair. He's been on the show before. It's been a massive hit. and I wanted to have him back on. He's a professor in the Department of Genetics. He's also at the Center for Biology of Aging at Harvard Medical School, and he is best known for his work on understanding why we age and how to slow its effects. In the last interview we had with you, blew up the internet. So, I wanted to dive in with a challenging question, an interesting question I think people are really curious about that we touched on a little bit, but we didn't dive in fully last time. is do you think human beings will ever be able to become immortal?

Yeah, that's a tough question. Here's the honest answer. No, I don't think so.

Never. In a thousand years, 10,000 years, never.

Well, never is a pretty hard statement. I would say that With the technology that I can envisage, even the best technology, give it a thousand years of development, I think we can live many hundreds of years.

Really?

Well, let's get into that later. I think we've got some new technology coming out of the aging field that makes the old stuff, even things just two years ago, look primitive. But immortality is so hard. I mean, we're fighting entropy. We're fighting the second law of thermodynamics, which is a very powerful law of nature. And really what we've discovered in my lab and some others around the world is that it's hard to preserve adult living things for a long, long time. You can keep them together and functioning for longer. We've got some species on the planet, particularly plants that can live thousands of years and many hundreds of years for some mammals, bowhead whale for example. But going immortality, you're fighting What turns out to be a loss of information? You know, we all understand the importance of information. Our computers get corrupted. We used to have things like compact discs and DVDs that got scratched. These are examples of the problems with trying to store information forever. You know, how long would an iPhone last? It's not going to last for a thousand years, that's for sure.

But if the information's in the cloud, then it can't be scratched, maybe digitally.

Scratched, but... Well, that's the saving grace. Maybe if we are able to upload ourselves somehow or rebuild ourselves from scratch, that's immortality. That's beyond anything that I'm seeing right now. I think a lot of people who say, oh, let's just download our brains into the internet, are underestimating the complexity of the human brain. It's not like just wires contacting each other. Every one of those wires is extremely complex, more complex than anything in the known universe. And so you put a few trillion of those together into one thing and it's very hard to map it without damaging it and let alone rebuild it.

So the brain wiring is more complex than anything in the universe.

Our brains are the most complex thing in the universe.

Do you think it's more complex than the understanding of God or source or the Creator?

I think that's pretty simple. You believe it or you don't. We've inherited brains from our ancestors that have consciousness and then we're able to ask these questions. Where do we come from? Is there a force beyond what we understand that gave rise to everything around us? Or are we just an accident of nature?

In your opinion, what do you think is an ideal lifespan for humans then? With the technology we have today and the technology we're going to have over the next two decades, what do you think is the ideal lifespan where we'll be functioning, healthy human beings that have memory and not just blobs that just last longer?

Yeah, that's a really good question. And I don't recall ever having been asked that one. Right now, the maximum human lifespan that's recorded at least, and even that is debatable, is 122 years old, the French woman Jeanne Calment. The thing about living that long, is that, and we often forget, is that that means she was still very active. I'm sure she was riding a bicycle around her village when she was 105. So if you live that long, you have this period of health where you don't have diseases. Aging brings on those diseases. And so when you think about extending lifespan, the important thing is to realize that you don't live longer in old age, you live longer in a youthful state.

What do you mean by that?

Well, we do have technology in animals, let's say mice, to make them live 20% longer. They don't live 20% longer at the end of life. They actually live 20% longer in midlife so that they don't get diseases.

They stay younger, longer, earlier.

Right, so that you can compare these animals. You can actually do this pretty easily. Actually, anybody could do it. You take a mouse and another mouse and you give a lot less food to one of them. or feed them every other day. And yeah, they'll be hungry. I think they eventually can get used to it. But what happens is you can compare those two mice or, you know, 50 mice in one group and 50 in the other. This is what has been done for now 80 years. And the ones that have spent some time in hunger are not always satisfied. They are remarkably different. Their coats look all shiny. They have very little cancer or evidence of cancer. They're running around the cage and the mice that have been eating as much as they ever wanted, which is kind of how we live now, most people, they are decrepit. They are not moving. They've lost a lot of their ability to remember things. They don't bother making a nest. It's dramatic and this has been done for monkeys as well. It's been done for Labrador dogs. It's a really universal thing in life. So to get to your question, Louis, actually, what's the optimal life? If you had the chance to stay young, why would you want to die? I don't think anybody who's healthy and has friends and is enjoying their life says, I want to die tomorrow. I haven't ever met anybody like that. You know, there's. There's pain, there's suffering, there's depression. But if you don't have those, why would you want to die? I mean, maybe boredom, but. You know, there are ways of living. Right.

You'd always want to live. You'd always, if you had a purpose, if you had community, if you were pain free, you'd want to keep living. I would assume if you were enjoying your life and you had love and connection and mission, then you'd want to live as long as you could. So what I'm hearing you say is that it's almost like food becomes the disease. If you don't manage it properly, it's what is the big cause of Death the more you eat.

Well, yeah, well, the food isn't the cause of death. We need food and we're not talking about malnutrition or starvation by any means. I want that to be clear.

Right.

We're talking about eating disorders here, but we are talking about not having three large meals a day. And the way to think about it is not that the food is killing you. What it's doing is it's turning off your body's protective mechanisms against disease.

So, creating some smaller stresses in the body turns on the immune system to fight against disease.

Yeah, well, not just the immune system, but that is a big part of it. It also turns on repair of DNA, it clears the body of old proteins that are just accumulating and causing issues, rejuvenates the mitochondria, which are those battery packs, the energy parts of the cell. A lot of things happen. We don't understand everything that's going on when animals or we are hungry. But we know that there are, at least we know of three main pathways that, and by pathways I mean biochemical workhorses in our cells, proteins that do good things. Three main pathways that are activated when we're hungry and go to work and tell other parts of the cell to repair the body and clear out the old stuff.

So in your opinion, what's the ideal lifespan?

Well, it's personal, but I would say I wouldn't mind living for 200 years. There's a lot I'd like to see in the future.

Right.

But I think if I reach 200 years, I'll still feel young. I might feel young, and then why would I want to die? It's all about being healthy. Now, what's the optimal lifespan for seven billion humans? That's a different question. We can't all live a thousand years and expect the planet to do well. But what I talk about in my book is that when you do the numbers, Allowing people to live longer and healthier adds huge amounts of percentage to the GDP. We're spending at least 17% of our GDP in the US on taking care of people who are sick. And most of that is spent in the last few years of life. And it turns out the longer that somebody lives, they actually are less costly to the healthcare system because they die quicker. And so if you draw a graph and, you know, I tend not to draw graphs, but this is what I have to. So we used to die off as a population like this and people would often get sick and stay alive for a lot longer in a sick state. I mean, now it's still possible to get cancer and suffer for 10 years trying to fight that disease, heart disease the same. But in a world where we can push that out and people tend to live to 100 years. We know that's possible. There are people that do this all the time. Then there's the very quick die off. And a lot of people get to that point, would get to that point, and then quickly die off. And that's a world that I think would be far better than this one, where from an economic standpoint and from an individual and family standpoint, anyone who's had a grandparent or a parent who became chronically ill, this is just nothing you would wish even on your enemy.

When it's like five years, 10 years, and it keeps extending where it's just uncomfortable suffering pain as opposed to what I'm hearing you say is live a great life and then once you start to feel a little sick, die quicker as opposed to die over 10 years of suffering.

That's the ultimate goal with this research and it looks feasible based on the work that's been done over the last 20-30 years.

Because essentially what I'm hearing you say is we're not dying effectively. We should be dying in a better way that's better for us as individuals, that's better for our families, that's better for the economy, the planet is what I'm hearing you say.

Right. No, we see that today as well, people who don't take care of themselves, who never exercise and eat the wrong foods and too much of it. You can see that those are the people that develop diseases in their 60s and 70s that are often horrific, you know, diabetes and having limbs cut off from lack of blood flow.

Yeah.

This in large part is preventable already. We know how to do that.

It's really sad. I know some people at that stage of life where it's just, you can't really come back from it. Once you've gotten to that point, you can't really reverse back to a healthy state. Is that correct? Maybe you can manage it a little bit, but it's not a reversible thing at that point.

If you asked me that last year, I probably would have said, it's not possible to come back from that. But this new work that I'm hinting at really does look like an age reset is possible in complex tissues and maybe one day an entire body.

Really? So someone who's 60s, 70s, who's got diabetes and it's really slowing them down and they're losing, you know, function in their, their body, you're saying that in the future, potentially, we could reverse that?

Right, theoretically. Now we haven't tested it in the context of diabetes. We tested it in the context of vision loss due to aging or due to damage to the optic nerve. But there it was very easy. In three weeks we were able to recover a lot of eyesight in a blind old mouse by resetting the age of the eye.

We haven't tested this on humans yet.

No, I'm trying to do that.

Wow.

In hopefully clinical trials will be two, three years from now.

That's amazing. So, I remember you saying in our last interview that you wouldn't want to live forever. But as you say, with research things change and last year you would have said something and this year is different now and you might want to live to 200, but if you were still healthy at 200, would you want to say, hey, let's keep doing this another century or Would you say, I'm healthy, I have love in my life, but I want to call it quits. Is there ever a time if you were healthy still, you'd want to call it quits?

I don't think so. I really don't. I haven't met a happy, healthy person who wants to die, have you?

No. So, it only becomes when it's a time of suffering, pain, immobility to function at life at a normal level.

Yeah, or depression. Let's face it, there are a lot of people on the planet that are not living great lives, you know, countries that are not as well off as these ones that we are. So I can understand there may be situations where you wouldn't want to live longer if you're doing a profession that every day is painful or just way too much work. You know, you and I have the privilege that we can do jobs from an armchair, but not everybody can do that. So I just want to, you know, realize, mate, that not everybody's in our situation, but hopefully if you have an extended lifespan, you'll be able to change professions if you're in one that you don't like and have the possibility of three, four, five different careers. Right.

Is it, in your opinion, more important to extend life or reverse aging or live better with the years that we currently have?

Huh. Well, yeah, obviously you wanna do both. And actually it turns out if you live better, during the years that you have, you will live longer. If you're making the most of life, you're enjoying your life, you have a career that you love, getting out in the outdoors, that will lead to longer life. We know that. So a good life actually leads to a longer life.

What's your thoughts on the difference between humans and artificial beings or some other species that the more we alter our bodies, in non-natural ways? Like, what's the difference between natural humans and kind of altered bodies with artificial beings?

Yeah, well, we're already there. I mean, what about our surroundings right now is natural? Or maybe even the air is different thanks to humans. So, you know, we're, I'm wearing a computer on my wrist, right?

I do.

Cyborg.

Yeah, we have a cell phone that has access to all the information in the world at our fingertips. It's probably eventually going to be embedded in our brain in some way in hundreds of years.

Sure, for sure. That's coming. But even things that we don't think about, the vaccines that hopefully we'll have soon, that's artificial, that's partly biologically cyborg. But these are early steps. Eventually our grandkids will have things integrated more into their bodies. I don't see anything wrong with that. It's just an extension of what we've been doing for the last probably few hundred thousand years as humans.

You mentioned vaccines. I had a doctor on a few months ago and I asked him, what's the misconception about the medical world that people have that they should believe in more? And he said, It's really sad when people don't... I'm paraphrasing this, but he said something like, It's really sad when People don't believe in vaccines because especially with kids, because they don't have the choice. And a lot of kids get sick and die without and they could just take a vaccine that could save their life. And I got a lot of heat for even allowing that to be said on my show from parents and mothers who are completely against vaccines because of the side effects that they believe it had or whether it's true or not. I don't know because I'm not the researcher. What are your thoughts on vaccines in general? I mean, should we be taking vaccines? Is this, you know, there's a lot of angry people that say, don't listen to the vaccine people, but what is science saying?

You want some more hate mail?

I don't know if I want more hate mail. I'm always trying to find the truth. I'm trying to find answers. And I don't want people to hate on you or me or anything. I just am like, okay, what's the information? And I always want everyone to do their own research. and figure out what works for them and make their own choices. But I'm just curious based on your research.

Well, my research is really just reading the scientific literature when it comes to vaccines. There have been a number of scientific papers that have been retracted that showed that vaccines were, for example, causing autism. So in the scientific literature, you know, this isn't me saying it. This is published work. in journals and other scientists have done other work and looked at that work and tried to repeat it. And it's come to the point within the scientific community that some of the original work that gave rise to these fears was unfounded and was not scientifically valid.

So in normal layman's terms, there were some research that said vaccines are bad or can cause side effects like autism. There was research that said that. And now what I'm hearing you say is there's other research out there that says that was not true.

Right. And when a paper turns out not to be correct, the journal or the author or both decide to retract the paper so it's no longer in the literature. Oh, that has happened to those original papers.

Now, you, you said scientists are always trying to prove themselves wrong every couple of years, so. all the science could be wrong still, we just don't know. But what we found so far is that it doesn't cause autism based on these scientific studies.

Well, yeah, I think if you ask a thousand scientists, 998 roughly would say what I'm saying, which is based on scientific literature. Now, please don't, you know, everyone listening, don't attack me. I'm not...

Right, you're not saying this.

I can read scientific papers and that's just devastating in fact.

Makes sense. I'm always trying to find the answers and the truth and I feel like it's always evolving and we're always trying to learn more stuff. I'm curious with all this artificialness in us right now, it sounds like none of us are real whole complete human beings anymore. If you take a vaccine, if you're wearing a digital watch, using cell phones, the air is different, the environment is different. It's almost like there's not a real human being anymore. What makes a human human? And as medicine improves, how will we know if we're no longer human?

Well, I found out last night, I took one of those little tests online and it said, I'm not a robot, which was good news, right? It came as a surprise. Beyond those little robot, I'm not a robot tests, We'll always be human, unless it's life synthesized from scratch or it's some other life form or a computer intelligence. I don't think we'll lose our humanity. Augmenting the brain, I think, is still we're going to retain our humanity. So I'm not so worried about that. I think more interesting is the debate about will artificial intelligence ever be close enough to be called human thought. And I think one day we may actually get there. Yeah, as soon as computers develop their own type of consciousness, and we model it based on the way we think, it's quite possible that- you- think it's.

Possible that computers could have human thought?

Yeah, sure.

Wow.

They could. It probably is going to be different than human because they We're not mimicking the human brain currently. Right. But, you know, let's say in a thousand years, there are some researchers even now that are modeling the human brain in a way that's different than your typical neural net that, say, Google is working on. The idea is to mimic nerve cells rather than mimic just computer connections. And these nerve cells, as I mentioned, are very complex. They have inner workings and they're actually analog devices, meaning they're not just ones and zeros. They have these waves that pass through, chemical waves that pass through, by mimicking an actual human neuron and then putting, you know, he's got millions of them, he can actually mimic what happens in thought and in a mouse brain and now he's building a human brain. So that's a new approach and I.

Think it solves a lot of problems. Two months ago, maybe three months ago, I decided to give myself an experiment and I wasn't happy with the results I was getting with my health. I was training hard, I was eating well, I was intermittent fasting for 16 hours a day, I was sleeping well, I was taking supplements, I was trying a lot of stuff and I wanted to try to lose some extra weight but also just kind of feel like there's some Little inflammation here from past injuries and sports. I was like, I just want to get rid of it. And I said, I've never tried a, you know, multiple day fast. And I remember you mentioning about just, Hey, eating less will help you live longer and help you get less disease, which will help you live longer. And I said, okay, I'm going to try a, I did a four days, no food, essentially. Four days, no food, water. I had a little bit of juice on some days and I had black coffee and I just drink a lot of water. It wasn't until a week after the four-day fast when I started to feel the effects. Sure, I lost some weight because I wasn't eating for four days and I felt healthier in general. I felt super focused and clear, but it wasn't until a week, two weeks later when I was like, huh, I just feel better. I feel lighter, I felt like more flexible, less inflammation. What is the power of doing a one day fast, a two, three day fast? How often should we be doing these types of fasting? And I want to make sure that I don't tell people go not eat for three or four days without talking to a doctor or nutritionist or something, but what is the benefit of not eating for a day? or two days? What does that do for our body long term?

Well, we're still learning, right? We've only just finished doing, we as a field of scientists have only just finished doing a lot of animal experiments, but we're now in a period where we're actually finally doing these in humans. So what do we know? We know that if you fast for one day, you're gonna turn on these three main mechanisms that protect the cell. Their names, by the way, there's one called mTOR, which senses amino acids that we eat. There's one called AMPK, which controls and registers how much energy the cell has. So if you eat sugar, you'll switch it off. If you're not eating sugar, you'll switch on. And then the ones that we work on, they're called sirtuins, and there are seven of these sirtuin proteins that protect the cell in very different ways, but all seemingly good. The question is, how much should you be doing? Well, we know from fasting for one day that you activate these defenses.

And these three defenses, we want to activate these three things as much as possible or once in a while.

Good question. I think it's better to do it once in a while. You don't want to always have them on. And the reason I can say that is based on animal studies, the best effects we've had and my colleagues have had is when you do things and let the body rest afterwards. For example, we did a study with resveratrol, this molecule from red wine that activates one of these sirtuins that I was telling you about. We gave it every day to mice or we gave them this calorie-restricted fasting diet, but it was when we actually gave them resveratrol every second day that we got the longest-lived mice in combination with caloric restriction. So that's just an example of many that we're finding that it's helpful to pulse the body and let it rest. And it does make sense that you want to have a hunker down period where your body is fixing itself and removing bad stuff, but then also a repair phase. So when you go back to eating regularly or you're not running marathons every other day, which some people tend to do. Then your body can recover and grow and heal. So yeah, long answer to your question, but I think pulsing it is the right way to go.

Is there a calculated approach to say, okay, if you're 225 pounds male, 37 years old, how many calories should I be eating a day? Like, is there a A perfect system to this of like, okay, if you eat 1000 calories a day for three days in a row, then you have 2000 for a day, then you fast a day. Have you figured out this process yet with rats?

No. No, it's not like that yet.

That can be interesting.

Yeah. The problem that we face in the field is, we were talking earlier, you and I, before we went on air about funding for science. We don't have tens of millions of dollars to run these clinical trials. We're always scrounging for money and always worried about what's gonna happen when it runs out. So we can do some experiments, but consider some of these longevity experiments even in rats and mice, they take about three years. And if you do it in monkeys, then your whole career is used up by one experiment. And so what we're trying to now figure out is, what's the right combination of what you eat, when you eat, and what supplements to take. And that combination is hundreds of thousands. And you can't run hundreds of thousands of these experiments.

Wow.

So it's hard to find the optimum. But in general, what I would say is that if you fast for one day, you get some benefits. If you fast for three days, something interesting happens. You turn on another level of cell cleansing. And I'll tell you a bit about that. So there's this process called autophagy, or some people call it autophagy. It is what it sounds like. Auto, which itself and phagey is eating. So you're self-eating and what that means is that proteins that are amazing.

You're eating yourself. You're killing it.

Well, eating the. Getting rid of the bad stuff, recycling the bad proteins as we get older and. Also, if we have damaged proteins, say if we eat a lot of burnt food, we will accumulate proteins that have a... oxidation is one, for example. And these proteins also are very hard to get rid of. They tend to clump.

Sticky.

They're sticky. And Alzheimer's disease is a good example of that, of proteins that stick together and just accumulate and you can't get rid of them easily. But autophagy is this process where the cells can chew these up and recycle the amino acids in those proteins. But our bodies, especially as we get older, do a pretty crappy job at doing that. And at least to things like macular degeneration, your degeneration and others. Now, what one day fasting does is it turns on autophagy and will clear out some of the proteins. But from my reading, if you do three days of fasting, something else kicks in. It's a different type of autophagy. It's called chaperone-mediated autophagy or CMA. And it was discovered by a good friend of mine in New York, Ana Maria Cuervo. And she has shown that this CMA process is really important for extending the health and the lifespan of mice. And I'm helping her a little bit with one of her companies to bring this to humans and hopefully treat diseases, for example, like macular degeneration. But anyway, long story.

So three days really starts to kick in the benefits. Is there a time when fasting too long hurts the body?

Well, sure. You need nutrition, right? Your body needs to. Needs amino acids to repair itself. I can't stress enough that we don't want anybody to lose so much weight that it's bad for them.

Yeah.

There are a lot of especially young people who can overdo it. You always want to have some adiposity of fat on your body. You need it for lean times and your body needs it for energy when you're sleeping, for example. But, so I think that going for a week is okay. I haven't done it myself. It's too difficult.

What's the longest you've gone personally?

I'm not that good at it. I've gone for a day. that's about it.

I tell you what, four days was tough, but it was also like once I set my mind to it and I was just like, I'm gonna commit to this. I also wasn't that hungry. I was just like, okay, I can go a little farther. It was just weird because I'm so used to eating every, I don't know, four or five hours. I was just like, is everything okay? But I felt the effects. It felt like it was getting better. My body was healing. I felt like the pain was starting to go away and I just felt clear and focused.

That's a common thing that people report is you'd think that you'd be distracted by hunger, but what actually happens once you do it for a longer time or you've done every other day eating for a while, or even in my case where I like to skip breakfast and have a late lunch or maybe even go straight to dinner, your body gets used to it. You don't feel those hunger pains if you drink a cup of tea or even a glass of water, it numbs any desire. That's when you know you're doing it right. But also what people report, and I can tell you from my experience, it also focuses the mind and you're not distracted at all. In fact, it's like a high that you get and I can get a lot of work done when I'm in that phase.

That's true. Do you think we'll ever be able to bring people back from the dead?

Well, we do now, but only after a few minutes. Now, I think if you've been dead for, like literally decomposing, you're not going to, but frozen bodies, still, that's pretty hard because there's been a lot of damage to those cells that have been, when they've been frozen. I wouldn't say it's impossible because there are animals that freeze in winter and come back to life, some frogs, for example.

Easy.

And fish. So it's possible, but we need to learn a lot more about how those animals are able to survive. They make these special antifreeze proteins and that protects their cells. And I don't think we're at a point yet where we can safely freeze our brains and expect it to thaw out and work again.

Yeah.

But again, you can't say never because even two years ago, I couldn't have predicted the kind of advances that we're seeing in medicine right now.

So there are frogs and some frogs and some fish that freeze for a period of time. Are they still breathing? Are they completely heart stops? What is the process?

Yeah, they're solid as a rock.

No breathing, no heartbeat.

No, they're solid.

They're dead, essentially.

Right.

And they come back to life?

Yeah, they thaw out.

And then they function. They're still swimming around. How long are they gone for? I mean, how long have they frozen for? Is this like a month, three months, all winter?

All winter, however long that is.

Wow. If we could figure out the process of how those animals do it, then potentially in the future we could do it, right?

There are ways to do this. And some people are talking about infusing the body with hydrogen sulfide or some other, maybe these proteins from frogs and allowing us to be- Wow.

From your perspective as a geneticist, Why do people have such different physical reactions to viruses like the coronavirus? Why are some affected and others not? Is it a genetic thing or do you think it's something else?

Well, it seems to be both. There are variations in the ACE2 receptor that seem to be involved, but most of it, as far as I can tell from my reading, is actually people's age. That's tenfold worse than anything else. Further down the list is diabetes, heart disease. But we're literally talking about aging here. Aging is your biggest risk. If you've been healthy your whole life and done the right things, that's going to protect you from dying from COVID-19. Because a lot of things go wrong as you get older that make you susceptible to the disease. One for sure is that your immune system is a lot less resilient. You know when we are exposed to a virus, our immune cells will multiply. Well, actually as you get older, you have a lot less ability to do that and there are even a lot less variants of your immune cells. So you can have a 100-year-old person has a lot fewer types of immune cells available. to fight an infection. We generally have clones of clones in our bodies as we get older, whereas when we're young, it's like a melange, a whole different set. So the immune system is screwed up, but there's also other issues. As you get older, you get more and more inflammation in general. There's a protein in the body, a complex of proteins called the inflammasome, and it controls your inflammation as you get older. it's harder and harder to keep that at bay. And so older people in general tend to have this hyper immune response that actually often can do them in. And it's not because the virus, it's due to the body overreacting to it.

Is there anything that people that are more susceptible currently that they could do to help combat the coronavirus or viruses like that without staying at home all day? and not being around it. Is there things that they could do to enhance the immune system and support them?

Oh, sure.

There are.

I mean, if anybody is out of shape or is carrying too much weight, those are the easiest things and most likely to work is to lose some of that excess weight and get moving. These things are known to greatly improve your immune system and including lowering inflammation. Now, not everybody can do that, right? People who are at an advanced age, you can't expect them to go out on a run or even perhaps to restrict their food. But, you know, people who are middle-aged, you know, like myself, I've been working out a lot more, exercising a lot more to make sure that my body's ready if I catch it.

What is exercise or shorter moments of bodily stress? Why does that boost immune system and help us anti-age?

Well, there are a lot of answers to that. But in general, the summary is that these protective pathways that we've discovered dampen inflammation when it's too high, and they also allow the immune system to attack a virus when it's needed. One possibility, and this hasn't been proven, but there's some evidence over the last six months of published work, is that as we get older, we lose the ability to make a molecule called NAD. which we work on in my lab. And without NAD, our bodies are not very well equipped to fight diseases, including infections. This inflammasome, which I'm kind of showing as a ball, but it's obviously much smaller, it is regulated by the levels of NAD.

What does NAD stand for?

Oh, nicotinamide adenine dinucleotide. Think of NAD as a small chemical that we need for life. It controls about 500 or so chemical reactions in our body. It's needed for those. We make less of it and we destroy more of it as we get older. But here's the thing, that two of these sirtuin proteins that we work on in my lab are controlling inflammation through this inflammasome protein complex. And as we lose NAD, one possibility in older people is that the inflammasome is now dysregulated and that goes crazy and leads to this cytokine storm that can eventually kill people. We have drugs that people are trying to dampen that down. And one of the things that we're trying now in a clinical trial is a molecule that the body can use to make more NAD, an NAD precursor we call it. And there are patients being dosed right now in, I think, four hospitals, or at least going to be four hospitals where We'll see if that is one of the ways to give older people resilience.

So the body stops making NAD, stops producing it, the older we get, and it's one of the causes that helps us defend against infections, inflammation, disease.

Well, we think so. What we see is when there's an infection, the virus actually chews up a lot of NAD. So cells, even if you're not old, the virus will deplete cells of NAD. And we think that that's a problem. Cells need NAD for life. If we don't have NAD, we're dead in about 30 seconds. But also, without that energy, you could easily imagine that the body is unable to fight the infection. But also, it could be an issue late in the viral infection where the body starts turning on itself.

At the moment, there's no supplements out there that you could buy that have NAD. to help you replenish NAD, is that right?

Oh, well, so, you know, I'm a Harvard professor. I don't haw any molecules or recommend any. I have to be very clear about that. But there are people, some companies that are selling NAD precursors.

Really?

Interesting.

Okay.

I don't endorse or recommend any of those.

Sure, sure, sure. Testosterone is also something that men lose that stop producing over time as well, which helps you. Does it just look younger or be younger?

Well, there was a set of very expensive clinical trials done with testosterone. And the results from those studies were that there wasn't a change in long-term health. The results were they were negative for slowing down aging. That said, you know, testosterone will help you build muscle. And having muscle is very important as you get older, of course, you don't want to be frail. And if you fall over, you want to be able to be resilient and not break a bone. Every few minutes, somebody falls, an elderly person falls over, breaks a hip and doesn't recover from that.

Oh, man.

So anything that you can do to be more flexible and resilient and have more strength, you know, that to me sounds like a good thing for elderly people.

Got it.

You're in your 50s or 40s, I don't know. I couldn't say I'm an expert on that.

I'm going to ask you another question that might be controversial based on a couple of previous doctors that I've had on. I had Dr. Roger Patrick on and I asked her, I said, Hey, what are some of the healthy foods that are marketed as healthy that in your opinion aren't as healthy as they claim to be? Essentially was the question I asked. And she said, grapes have a lot of sugar in them that spike my blood pressure. I think she wears like a glucose monitor, so she's monitoring all of her food and constantly testing it. She said, when I was eating grapes, like my glucose levels went way up, skyrocketed, and I realized that that's not good for the body to have, you know, grapes, a lot of grapes, and you can transition it into having blueberries or something else that might be better for the nutritional benefits. I put that online and people slammed me for that. And then Dr. Gundry, said that he doesn't think modified apples the way they are now, how we modify them, how they're so big, how they're full of so much sugar. He's like, I don't think that's good to have these big apples that are modified because of the sugar and the fructose in these big apples, like a Honeycrisp or something. And, he was saying we should be having a lot less fruit because of the fructose levels. what's your thoughts on fruit in general? Should we be eating fruits every day? Is it something with, you know, I've been heard in the past. Like, we only used to have fruits right before the winter to kind of store up the fat and, and a seasonal thing. There's a lot of fruit eaters out there that believe in eating fruits, only fruit all day. I'm just trying to find the answers. I don't know the truth of the matter, but what's your thoughts based on research?

So research, we don't research fruits of course, but we do research the effects of sugar on the body and it's not good.

So try- and is that all sugar or is that fruit sugar or refined sugar? What's, do we know that?

Well, there's glucose and fructose, okay? So it doesn't really matter where you get it, these are just chemicals that's the same chemical wherever you get it from. Glucose, you need glucose, right? Again, we die without glucose. But the foods in our world are so full of sugars that we're constantly feeding ourselves more sugar than we ever would have experienced even just 100 years ago, or 50 even. So where do I come down on this? Well, let me tell you from my own experience, it's probably better to give you my example than preach to others.

Yes.

I definitely like fruit and I eat fruit and I encourage it with my kids for sure. But it's a balance. You want the most nutrition and vitamins and the lower amount of sugar. And on a scale of that ratio, I think Rhonda Patrick's right that grapes have more sugar than nutrition compared to other fruits. The types of fruits that I like to have are ones that have lots of polyphenols, colored fruits such as blueberries, blackberries, those things. You don't want to eat too many of them, of course, because then you're basically eating tons of sugar in it anyway. But, yeah, blueberries I would have in a yogurt in the morning if I had had some. Right. The other fruit that I think is worth looking at is cantaloupe or rockmelon. that I believe has the most nutrition versus sugar of any fruit. So we try to eat those kind of melons as well. Watermelon probably isn't in that category, but we still eat it in summer. The point in my family and in my life is we're not so strict that we avoid every type of food. I'll even eat a hamburger or whatever if I feel like it. But most of the time I try to focus on on plants and have meat as something like a reward, even though I much prefer the taste of meat than just leafy vegetables. But I think that it's borne out just looking at people who live a long time and cultures that have a lot of elderly people over 100. The type of foods they typically have a lot more plant than just pure meat. And I'm gonna get hate mail as well from the carnivores. But it's important people know, I'm not saying don't eat meat, I'm just saying the kind of balance if you want to focus on types of foods for longevity, that's what the data says.

Gotcha. Do you know if the people in the blue zones who are living over a hundred, are they eating, I'm hearing you say they eat more plant-based, are they eating lots of meat, lots of fruit as well, or are they limiting intake on some of those areas.

Well, they seem to do all the right things. So it's, don't eat a lot on the island of Okinawa. They tend to stop eating when they're only 70% full, which is a very good idea.

Gosh, it's like I, I keep eating until I'm 70% over full. Yeah.

Then you can regret, then I regret it. Yeah. But you also, you, you work out.

More than I trade hard. Yeah. Yeah.

They tend to eat the right types of foods, which are packed with these polyphenols, these little chemicals that are found in plants, particularly when those plants are stressed out. They don't eat a lot of processed foods, which kills a lot of these vitamins and polyphenols as well. They eat colored foods, which as I mentioned is a good thing. They tend to have good social life. They tend to move a lot. They do gardening. They do walking as they get older. These are all things that just make a lot of sense anyway. We know that exercise and eating these healthy, fresh foods are good for us no matter how old we are. In terms of chemicals in the diet, olive oil, for example, has a lot of oleic acid. And a lab just last year showed that oleic acid works just like resveratrol to activate the sort of 2 and 1 enzyme, this protective defense enzyme. So normally you would have to be hungry to turn this on. this enzyme on that we work on. But now we know that you can probably take some resveratrol or some olive oil to activate it artificially.

Well, Gundry would say the whole purpose of food is to get as much olive oil in your body as possible. He's a big believer in olive oil and how it helps you anti-age. So, this is fascinating stuff. Again, I want to make a note that I hope all the fruity eaters out there Don't hate on us. I'm just trying to find the answers. And David is giving some of the research that he's seen from his experience as well. I got a couple of final questions for you, David. I always love talking to you. I want to talk to you many more times in the future because I feel like every six months, you're going to have new information for us. You said that science is driven by the question, not the technology. What are the biggest questions you have out there right now or science has out there right now?

Well, there's a big one that we're chasing right now. As I mentioned earlier, we found that we can reset the age of a cell and literally turn its age back. There's a clock in the body that we can measure. It's little chemicals that bind to our DNA as we get older. And by measuring the rate of those changes, think of it like plaque on your teeth accumulating, the older you get, you know, as long as you don't scrape it off, the more you'll have similar to how DNA accumulates these chemicals. We can measure the clock. We can predict how long you're going to live based on that clock. And what we found is we have a new, currently it's a gene therapy, but hopefully one day it could be a pill that resets the clock and cells go back to acting and being young again.

No way.

Yeah, that's how we restored the vision of those old mice. We put therapy into their retina.

We can reverse, reset the clock of time on our cells in our body.

Well, in mice, yes, and in human cultured cells in the dish, yes. We will know in a few years if it's true for humans.

What would that mean if we could do that?

Well, this is why I'm more optimistic than I was even a couple of years ago. We know that we can reset the age of cells in complex tissues like the eye at least once. And it looks like it's going to be a long-lasting change. But we don't know, but I'm optimistic that we can reset multiple times. Imagine that.

Amazing.

And so the big question that we're trying to understand is similar to how a DVD gets scratched, how do you polish that DVD and allow the cell to read the young information again?

Wow.

And it's quite a a big idea that our cells have a backup copy of youthful information. How do they know which of these chemicals to get rid of to make the cell young again and not go too young that you become a tumor or basically an egg cell again? We don't understand that yet. So we're trying our best. We've made some breakthroughs. We know some of the machinery that allows this to work. But ultimately we still don't know what form this information of youth is in. For instance, it could be a new type of chemical that is added to the DNA when we're an embryo or when we're very young, and we still have it in our bodies that our cells can recognize and use that as the reset switch. It could be another type of molecule, could be a protein that binds to our DNA. So we're looking very hard for where that information is stored, and when we figure that out, then I think we can really have a good handle on age reversal.

Science is fascinating. Now I know why you love being a scientist. Is there a way right now to predict like when someone would die based on their current life, their cells and say, okay, you're gonna live from 84 to 87 range based on what you keep doing at this stage. If you don't change anything.

Yeah, yeah.

Really?

Some companies selling these clock tests, you can have either a swab in your mouth or a blood test. No way.

It'll tell you to predict the age you're going to die.

I don't know about specific companies, what they're offering, but in the lab, we can do that. A good friend of mine, Steve Horvath, at UCLA does this routinely, and he's published work that can predict within a few years of when you're going to die if you don't change your habits. And people who smoke, people who are overweight, have a faster clock. There's no doubt that you can control the rate of your aging with how you live your life.

What are the effects on a lot of people moving from smoking cigarettes to vaping? I feel like vaping is taking over the world right now and a lot of teens and smokers who are saying, okay, well this is better for me. I'm going to vape now and it's not going to be as bad for me. How bad is vaping on the body? in the body's lifespan?

Yeah, we don't know. Somebody needs to test that.

I feel like that's gonna be a big issue in the next five, ten years.

Yeah, yeah. Well, so my personal view, having a mother who died of lung cancer from smoking is that our lungs are pristine organs. They need to be free of particles, free of foreign material. to work well. They're very fragile and putting anything foreign into your lungs to me doesn't make any sense.

Vaping, smoking, any type of inhalation of a toxin.

Right, right. I mean, there are fewer toxins, I understand it, with vaping, but still we're learning that it's not risk-free.

Okay, I got one final question for you. From your study of biology, do you think aliens exist?

Yes, there is a calculation, a formula that you plug the variables in and the one thing that we tend to underestimate are the number of stars in the universe. And they're actually, it's not infinite, but it's close to it. There are so many possibilities that there has to be life out there. It's a certainty.

It's a certainty. Yeah. Wow. Why is it a certainty?

To get to know them is another thing. Some of these life forms are going to be so far away that we can never communicate with them, unfortunately. But yeah, the science says they're out there. They've just got to be. The odds of them not being there is infinitesimal. Now, the problem that comes up is that just like we're learning as human beings, we tend to evolve destructive capabilities. The reason that we are survivors is that our ancestors wiped out the neighboring village, plundered and raped, you know, pretty routinely. We are not necessarily good animals at this point. We've got laws which prevent people from going, you know, too rebellious. But, you know, deep down, we do have an evil side as a species, not everybody individually. And it's probably true for aliens as well that They've come up the same way we have and have a bad side as well. And that leads to destruction. And it could be that every civilization eventually wipes itself out after 20,000 years.

Yeah, I mean, because if a foreign thing came here, we probably wouldn't be welcoming something new, foreign with welcome arms. We would be worried living in fear, stress, anxiety, and to want to protect ourselves, kind of like, Whatever, anytime someone settled into a new place, there's probably already, there was some type of worry, fear or stress, right?

Exactly. Whenever I see a human trait, my mind goes to why does it exist? And whether or not it's being altruistic and kind or evil and a liar or someone who commits adultery, these are all traits that have at one point in our history been advantageous and we are descended from those people. But, you know, we shouldn't, we shouldn't be slaves to our DNA. This is why we have a big brain. We should be able to choose a path of survival and kindness where we can all live on this world and enjoy, you know, the freedoms and the luxuries of not having to worry about food.

David, you're one of the smartest and nicest scientists out there, my man. I really appreciate you and acknowledge you for constantly doing the research and constantly putting yourself on the line based on things you discovered 10 years ago, two years ago, where you're constantly learning new things and sharing that wisdom with us. You're doing great work and I really acknowledge you for that. You've got a great book out there called Lifespan. If people want to learn more about how they can really live longer, live healthier, you're on social media, David Sinclair on Twitter, David Sinclair, PhD on Instagram. we got to have you come back every six to 12 months for sure because I have so many questions that I want answered and I know your information is really helpful. And in the last interview, I asked you about your three truths and the definition of greatness. So if people want to hear that, which was an amazing interview, go back and listen to that episode. You can hear about David's three truths, which the third truth was the most inspiring for me. I'm not sure if you remember, I'm not going to say it, but the third one was the most inspiring. And is there any final thoughts you have, David, before we let you go today?

Well, thank you for what you do, Louis. It's actually great to be able to have a platform to be able to speak to people directly rather than through other types of media where scientists' words just get misconstrued and hyped. So this is, I want to appreciate and say to everybody listening, this is a fantastic world we live in where we can, through folks like you, talk directly to the public.

For sure.

And your podcast has been one of the best that I've been on. Some of the questions you've asked me, no one's ever conceived of asking me those. So thank you for that. Final thought. What's on my mind these days is the word kindness. I brought it up earlier. We're in a world where there's too much arguing partisanship. And we're facing an enemy right now. We're trying to get through this period of our history. And things are going to get tough. Things are tough for many people already. And I just want everybody to remember, it's easy to say we're all in this together, but what I really want to say is that let's be the best people we can be. And kindness is what comes to mind. And if we can just do that, I think we're all gonna get through this, okay?

My man, David Sinclair, thanks so much for being here, man.

Appreciate you.

Appreciate you, too. Thanks, David. If you want to learn about the key foods you need to eat to master your health, make sure to watch this video right here. Humans who eat two cups of mushrooms per week do not get Alzheimer's disease. And it's because... Two cups of any type of mushroom? Any type you want. Just go to the grocery store. Go to the grocery store. Get some mushrooms.