PROFESSOR DAVID SINCLAIR | Can Humans Live For 1000 Years?

David Sinclair is a Professor in the Department of Genetics at Harvard Medical School and co-Director of the Paul Glenn Centre for the Biological Mechanisms of Ageing. Today we hear from a scientist at the cutting edge of longevity research as Professor Sinclair gives us a fascinating insight into the world of anti-ageing. Expect to learn how and why we age, why stabilising the epigenetic landscape may enable a human to live for 1000 years, exactly what tactics Professor Sinclair is using himself to try and extend his life and how fasting, Sirtuins and NAD can be used to promote health and reduce diseases. Extra Stuff: David’s New Book - http://lifespanbook.com/ Follow David on Twitter - https://twitter.com/davidasinclair Inside Tracker - https:// www.insidetracker.com Recommended Books - https://www.amazon.co.uk/shop/modernwisdom Nick Bostrom on Sam Harris - https://podcasts.apple.com/gb/podcast/making-sense-with-sam-harris/id733163012?i=1000432217348 - Listen to all episodes online. Search "Modern Wisdom" on any Podcast App or click here: iTunes: https://apple.co/2MNqIgw Spotify: https://spoti.fi/2LSimPn Stitcher: https://www.stitcher.com/podcast/modern-wisdom - I want to hear from you!! Get in touch in the comments below or head to... Twitter: https://www.twitter.com/chriswillx Instagram: https://www.instagram.com/chriswillx Email: [email protected]

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Chris Williamson?

  Howdy friends. I'm coming to you from America, as is this podcast, but not the same trip. Podcast land sometimes has an odd sense of serendipity when it comes to the scheduling. So today, I am sitting down with Professor David Sinclair from Harvard Medical School. Now, I first heard David on Joe Rogan's podcast and was blown away by his insight. He is an expert in anti-aging and longevity. He has more companies than I think even he can remember, and has essentially the same as a knighthood in the UK, but the Australian version. Oh yeah, and he's one of Time Magazine's 50 most influential

• 0:41Chris Williamson?

  health professionals on the planet. So in short, he knows what he's on about. Today, we're learning about what makes us age, how our cells and genes degenerate and get damaged over time, and what techniques are available to actually slow, stop, and reverse this process. That's right, making animals younger than they are. Sounds like science fiction, but it's just another day in the life of David's laboratory. So yes, strap in and get a notepad and pen out for this one. Also, I'm going to predict a number of inquiries about who Inside Tracker are, after me and David both extolled their virtues on this

• 1:21Chris Williamson?

  particular episode. So if you're interested, head to www-insidetracker.com to find out more about their service. David uses it, and if it's good enough for him, pretty certain it's good enough for the rest of us. But for now, please welcome Professor David Sinclair. Oh yeah, P.S. There's some special behind the scenes footage of David's laboratory and Harvard Medical School, along with me taking far too much caffeine on the YouTube channel. So go and watch the episode on there if you fancy it.

• 1:50Speaker 01

  Mr. President, my company informed me of the explosion on our rig on October 2nd. Causing massive water displacement and triggering a tsunami. If y'all keep the blame on me. Tom Cruise is.

• 2:01Speaker 02

  Digger got us into this mess, and Digger's gonna dig us up. From the director of Birdman and the Ravennet.

• 2:07Speaker 03

  What would happen if I stopped going? You stall, you freeze to death, that's what.

• 2:11Speaker 02

  With great power comes great deniability.

• 2:14Speaker 03

  I'm not the first nanny.

• 2:15Speaker 02

  Digger. See the trailer online. Only in theaters October 2nd. Rated R. Under 17 and under 17.0 without parent.

• 2:36Chris Williamson?

  Ladies and gentlemen, welcome back. I am joined by Professor David Sinclair of Harvard Medical School. How are you today? I'm doing really well, guys. I'm very, very glad to be here. I'm off to see your friends at InsideTracker later on. I'm gonna go straight over there and have a sit down with them and go through my, my results. See what, see what they've got to say. Oh, really? You've had your blood drawn? I have indeed, yeah. That'll be exciting. I went to Quest Diagnostics a week and a bit ago in California. And I went through my results with Stacy. If it's not, if she's not called Stacy, I'm gonna be in so much bother. With one of the analysts at InsideTracker and they took me through all of my stuff earlier on, actually. Which is super interesting.

• 3:20Chris Williamson?

  So are you older or younger than your actual age? I am thirty-one in real years and the inside of my body's thirty-six, unfortunately. That is because glucose being out of range weights very heavily. And the only thing I've got is slightly out of range glucose. And my lipids are a tiny little bit out as well. So I need to eat soluble fibre.

• 3:50Chris Williamson?

  Yeah, you'll, you'll enjoy that.

• 3:54Chris Williamson?

  Soluble fibre. When I was looking at the list of potential groups of foods, it was just twenty different types of beans. And I was like, I have, I have no types of beans in my diet. Like a baked beans, like, does that count as a bean? I'm sure it does. It has the desired effect, I bet. It does indeed. So the first question I've got for you, what, what do you do here? I know we're in Harvard Medical School. I haven't got the first idea about what it is that you do.

• 4:26Speaker 04

  Well, so I I come in every day to my lab. Uh, there's about thirty to thirty five people in in my lab.

• 4:34Speaker 04

  And I instruct them to discover really cool stuff. And that's basically my job. Uh, and they'll come to me and they'll say, I've got an idea to discover something. And I'll say, that sounds good, go do it, or that sounds really boring, don't bother doing it. And by the way, how much is that gonna cost? And they'll tell me it's gonna cost about two million dollars. So it's my job to bring in the money and let them uh figure it out. But the theme of my lab is focused on aging and has been since I started the lab. Uh, about twenty years ago here at Harvard. And so I I run a center for aging research here. And we are really working, uh, not just on trying to understand why we age,

• 5:17Speaker 04

  but also how do we slow down and reverse that process as well?

• 5:22Chris Williamson?

  And that's all being conducted here, but also offsite at one of your multiple companies? Or is it mostly here or is it? How does it work?

• 5:31Speaker 04

  Well, there's a giant ecosystem. Uh, this is the Menlo Park version uh of the ecosystem where we do the very basic discovery. We can ask fundamental questions about what is the clock of aging? Uh, can we reprogram the body? Is it safe? Uh, and can we extend lifespan? Mostly of animals we work with here. Uh, these are um laboratory animals. Uh, outside of the university is a a network of companies, um, institutes, colleagues, collaborators. Um, literally thousands of people around the globe, uh, Europe, Asia, Australia and others. Uh, all working with us on trying to understand these questions, answers to these questions.

• 6:15Speaker 04

  But also what makes my lab rare uh and unusual is we're very innovative. So that we file patents once every few months. We spin out a company uh at least a couple of times a year. Uh, and the reason for doing that is not because, well, I do like starting companies, but that's not why I do it. I I do it because I'm not satisfied with just publishing work. I feel that my role on this planet, if I have one, is to try and help people with their lives, to live longer and healthier and more productively. And just making a discovery in a yeast cell or a mouse isn't doing it for me. That's just part of what I'm here for.

• 6:55Chris Williamson?

  You need to apply that as well.

• 6:57Speaker 04

  Exactly. So most of the companies that come out of this lab are biotech companies working on medicines. But we also do a whole range of other things. We have biosecurity, so protecting the world from pathogens and and other nasty things that can go on. Um. We also work on bioinformatics, so trying to understand, so like Inside Tracker, how do you estimate somebody's age and help them with their living and what they're eating? Um. But mostly it's molecules that we hope will be drugs one day to not just treat one particular disease of aging, say diabetes or heart disease or cancer, but to have a radical type of medicine uh that would actually slow down all diseases as at once with a single pill.

• 7:40Chris Williamson?

  Is it likely that there is a, I don't know whether panacea is the right word, but a out there, a particular way to manipulate molecules which will be the equivalent of an aging panacea?

• 7:53Speaker 04

  Uh. Well, there certainly will be. Uh. A lot of people who hear that we're close to finding something that'll slow down aging, um, they're right to be skeptical because

• 8:04Chris Williamson?

  Sounds like turning back time, right? Like literally feels like, oh, you're slowing down aging. Yeah, cool. And can I go and get in a DeLorean at the same time, please? Is that all right?

• 8:12Speaker 04

  Right, but actually figuring out how to slow down aging or reverse time is is a lot easier than building a time machine. And I think it's going to be easier than curing cancer. Uh. It's not that hard. We actually understand as a field over the last twenty years, what controls aging. We have genes in our body called longevity genes that slow the process down. And in recent breakthroughs, just in the last couple of years, uh, the field and my lab have discovered that you can reprogram the body and reset the body's clock to be young again. And when I say body, I mean, it's still in the in the lab. But we hope that within a couple of years, we'll be actually be doing human clinical trials to literally reverse aging in cells.

• 8:52Chris Williamson?

  What's the mechanism that this works on? Can you take us through it?

• 8:55Speaker 04

  Yeah. Well, there there are three main approaches that we're taking. Um. And I'll just summarize them. The first that we've been doing for a long time is activating the body's defenses against aging. So normally you have to be hungry or exercise to do that. We've found genes and molecules that you can give to animals and and to people actually that slow down the effects of aging. So that's one. So that, think of that as activating the body's natural defenses against deterioration of disease. That we've been doing for twenty years at least. The second is to delete cells that are actually causing the problem. So there are cells called senescent cells that you might think of as zombie cells. And those zombie cells are causing havoc and you can actually get rid of them.

• 9:39Speaker 04

  And when you do that in a mouse, it'll live longer and be healthier. Then the third approach, which is much more recent, but much more powerful than any of those, is called partial cellular reprogramming. And my lab and some others have actually shown, just a few others around the world, that currently if you put a combination of resetting genes into cells in the dish and actually in an animal, you can quite literally reverse the age of those cells so that they become young again. And in mice, what we're discovering, and we're writing these papers up now, is that you can drive aging forward and accelerate it with this technology and you can reverse

• 10:20Speaker 04

  it just as easily and make cells behave as though they're almost embryonic. I'll give you an example.

• 10:27Chris Williamson?

  Yes.

• 10:28Speaker 04

  When we're, when we're born, one of the first things that ages in our body is our, is our spinal cord and our central nervous system. And you, you might say, well, David, why do you say it's aging? Well, a young neuron will be able to repair itself and regrow. But we know that if we damage our eye, our optic nerve, or our spine, we're never going to walk again or see again. But if you're young or if you're a salamander, you can actually regrow the, the central nervous system. So we've got ways now of reprogramming those cells, or an entire mouse, to make it ostensibly younger again and they regrow their optic nerves so that they can see again.

• 11:10Chris Williamson?

  That sounds like science fiction.

• 11:14Speaker 04

  I thought so too, but in May this past year, two thousand and eighteen, one of my students who was working on this, Wan Chang, he thought it was never gonna work, but he thought he'd try it anyway. So he injected this gene combination into the eye of a mouse and he damaged the optic nerve so that it was all dying, turned on the system and it grew back. And he texted me the picture and said, I cannot believe this is working. And I said, you know what? I can see the future right now. And he's since tested it on glaucoma, which is damaged due to eye pressure. He's tested on, on, just on regular old mice that don't have good vision.

• 11:56Speaker 04

  I'm almost fifty and I can already tell my retinas not as good as it used to be. We can actually treat old mice and get them to see like a young mouse within just a few weeks.

• 12:09Chris Williamson?

  I, to me, aging feels a little bit like the passage of time. So it feels like something that you are along for the ride with. And it would appear that that's not quite the case and that, I think I'm a good avatar for the layperson. I understand that cells regenerate and I think that your entire body, every cell is redone within a particularly, not a hugely long window of time.

• 12:40Chris Williamson?

  But for some reason, the concept of them actually growing or getting younger just seems odd. It feels like we would be going back in time.

• 12:50Speaker 04

  Well, we're going back in age and you can disconnect biological age from chronological age. The, one of the main reasons I believe we age is that we have a, we have what's called an epigenetic clock that ticks over as we get older. Due to time, but also how we treat our bodies. If we smoke, we don't exercise or we're obese, the clock will tick faster. But now that we understand what the clock is, we're finding that we can actually revert that age and get the biological clock to go backward, not just slow it down. And so those nerve cells that I was talking about regenerating. We do literally make them biologically young again. And how that actually happens is on the cutting edge of science right now, but we have some clues as to

• 13:35Speaker 04

  how the cell is accessing the youthful information that is locked away inside it.

• 13:40Chris Williamson?

  Can you explain how that works?

• 13:42Speaker 04

  I can to the very extent of what is known to science right now.

• 13:46Chris Williamson?

  Yes. And your best, your best idea, is it what's on this whiteboard?

• 13:49Speaker 04

  Some of it, that's a messy diagram that I drew trying to explain it.

• 13:54Chris Williamson?

  It looks like bunches of grapes, those are some mice running towards other mice, that's a little boat at sea. Um, that is, that's a cloud, that's a cloud with birds coming out of it.

• 14:03Speaker 04

  It's exactly right. You've solved it.

• 14:05Chris Williamson?

  Cricket balls there at the top.

• 14:07Speaker 04

  Yep, actually, that's a tennis game within our cells, literally. Uh, well, the, and maybe not, not literally, you don't have tennis balls, but what we do have are proteins that act like tennis balls that bounce around inside the cells going from one thing to another, and that's a tennis game. And what we've discovered is that normally those tennis balls, those proteins will sit on parts of the genome to tell a cell, it's a liver cell, or it's a brain cell, muscle cell.

• 14:36Chris Williamson?

  So it doesn't regenerate the wrong thing?

• 14:38Speaker 04

  Right.

• 14:38Chris Williamson?

  Okay.

• 14:39Speaker 04

  Right. And those are laid down, those structures in the cells are laid down when we're born. So a muscle cell is not going to give rise to two liver cells, it's going to give rise to more muscle cells.

• 14:48Chris Williamson?

  Yes.

• 14:48Speaker 04

  And we understand pretty much how that works. These proteins that sit on the DNA, they control which genes are on and which are off at any one time.

• 14:55Chris Williamson?

  Okay.

• 14:56Speaker 04

  But those balls actually get distracted. And so here's where the tennis analogy comes in. We can distract those proteins by doing things to the cell. One really great way of distracting them is to break a chromosome. And then those proteins, they panic and the cell pulls them to the break to help repair the broken chromosome, leaving those genes at, to, to wreak havoc for a short period. But then, once the repair is complete, they'll go back and re-establish that program again, so that the liver cell stays a liver cell. The problem is. With the tennis analogy, if you keep whacking balls back and forth over seventy or eighty years, you're gonna lose balls, you're gonna not hit them back to where they came from.

• 15:40Speaker 04

  And it ends up being a huge mess. And so there's balls scattered all over the court. Or in this case, the those proteins that were once laid down in the right place to turn the cell, the genes on at the right time, are now scattered all over the cell, the nucleus, and the cell loses its identity. So a liver cell is, an old liver cell is more like other cells in the body. And actually, they forget to be liver cells.

• 16:04Chris Williamson?

  Okay, so can you explain the difference between what would look like a young cell and what would look like an old cell? Or what is, what categorizes that? That's someone who needs to know what a young liver and an old liver cell look like. That's what that person.

• 16:19Speaker 04

  Well, I can pretty much guarantee you that it's someone calling me to find out how much of a certain molecule they should ingest. That's usually the.

• 16:26Chris Williamson?

  Is that really what you're getting at the moment?

• 16:27Speaker 04

  Uh, hundreds of emails a day.

• 16:29Chris Williamson?

  Really?

• 16:30Speaker 04

  It's a lot.

• 16:30Chris Williamson?

  Well, I mean, this is the Joe Rogan effect, isn't it?

• 16:34Speaker 04

  Well, it's always been a lot, but yeah, Joe did increase the.

• 16:38Chris Williamson?

  Orders of magnitude.

• 16:39Speaker 04

  Of interest, for sure. Also, I'm fairly rare as a scientist. I talk about research as it's happening. And it's it sparked people's imagination.

• 16:50Chris Williamson?

  To segue briefly here, one of my friends who spends a fair bit of time on Reddit mentioned that him and some of his buddies loved the episode that you'd done with Joe, and that they were part of the R slash longevity thread on Reddit. And I just decided that he would post, one of my buddies is going to go and do a podcast with Professor David Sinclair, does anyone have any questions? And I thought it would be like, I don't know, how many, how many pieces of fruit and veg should I eat a day? Or how long is the optimal window of a fast? Like, you know, sixteen eight? Or should I be doing like an eighteen six? Or whatever it might be. And the list of questions that I had to try and translate,

• 17:33Chris Williamson?

  I've not even, they're in Evernote, but they're just staying there because I can't pronounce half of the words that are in there. But I think one of the things that it definitely did identify to me is that longevity at the moment appears to be a very emerging field within kind of the, the. General public or becoming more of a general public concern.

• 17:52Speaker 04

  Yeah.

• 17:53Chris Williamson?

  I mean, everyone's aging, right?

• 17:55Speaker 04

  Right. Well, we've always been aging as a species for ever since we were, you know, primordial cells in the soup of four billion years ago. And we've always been conscious of our mortality. But I think there are two things happening because one is that the science is mature and it's no longer an if, it's just a when. We have the technology, we understand how to slow down aging, maybe even reverse it. And the other is that the world I see is bifurcating into two types of people. Those that want to understand a topic in detail, so your listeners are those type of people. And God bless them. This is the level of detail that typically members of the public would never know about. And then the rest of the world watches cats playing pianos and stuff.

• 18:38Speaker 04

  But thank goodness, there are people who really care about the world and what's happening and want to learn in detail beyond what typically a newspaper used to tell people.

• 18:48Chris Williamson?

  I agree. I think that we've emancipated the ability for people to to learn in as much detail as they want. And there is a there is a horse for every course with regards to what people want to learn. You're totally right that for myself, I we get comments all the time on the YouTube videos and stuff like a too long didn't read, like can someone do a TLDR of this particular podcast? And I'm like, if you want a shortened version of this, there's someone or if you want to watch something which is short, YouTube is awash with three and four minute videos. Like, feel free to go and watch that. I particularly, and I know that the listeners do as well, they enjoy the nuance and the subtlety

• 19:29Chris Williamson?

  and the detail and and deconstructing things down to its component parts over the course of one, two hours. That's what I think is important. And it definitely sounds like that's helping people to buy into more difficult topics potentially like this.

• 19:44Speaker 04

  Oh, for sure. Because when a newspaper reporter, not all of them, but many of them over my career, which now spans twenty five, thirty years, they latch on to this and it's always hyped. Oh, we're going to live forever. You should drink more red wine, blah, blah, blah. And I can tell you, as a scientist who's spent his career working on the cutting edge of research at Harvard Medical School, publishing in the world's best scientific journals, it's really frustrating and it's actually taken a lot of willpower to make it through those times because the now, almost every time what I say comes out changed.

• 20:19Chris Williamson?

  You get the bastardized version of whatever it is that you've said.

• 20:22Speaker 04

  And no wonder the public says, yeah, this is another stupid story. It can't be true. But if you listen to two hours of someone like me talking, you really do realize that the science is way more advanced than people ever knew about. And as a scientist, I just, you know, thank heaven. Thank people like you who can actually allow people like me to reach many people at a level that never was possible before.

• 20:47Chris Williamson?

  I totally agree. Um, how much, this is a question that's been percolating around in my head. How much do you think the increasing interest in longevity with the general public is due to a fear of death?

• 21:02Speaker 04

  Uh, probably most of it, most of it. Deep down, I think we're all afraid of dying. And maybe not that actually the day we die, we're not afraid of, I'm not afraid of dying. I've looked to death in the face a few times in my life. It's not that scary, but I think we're all fearful of, of not being around. It's gonna be pretty boring. We're never, probably never going to see our loved ones again or our friends. That's pretty sad if you really think about it. And it actually takes a lot of courage to think about our own mortality. Mostly by the time we're age six, we forget about it and don't think about it again till we're about fifty years old. Uh, and that interim period, we assume we're immortal. Of course, we're not, and I don't think we ever will be.

• 21:47Speaker 04

  Uh, but I think what's going on is that, that once you realize that something can be treated, potentially, then it gets exciting. A hundred years ago, people used to say, you know, cancer and gangrene, dying from a splinter, childbirth, these were things that were just the way life is or was, just the way it goes. And so people didn't really care that much about it. Once antibiotics were developed and other medical treatments, people actually were okay talking about it. And the same is happening with aging right now. Uh, the best analogy I could give in terms of human history, it's like the Wright brothers where in nineteen oh two, they built their Wright flyers and we're strapping on engines and seeing where we can fly.

• 22:28Chris Williamson?

  Yeah, you are right that the frame is moving with regards to the fidelity and the resolution with which we see life, that a splinter could have killed you a hundred years ago, or that I've read an article not too long ago about the fact that so many prehistoric people died from issues with their teeth, that they had mouth infections, that was one of the, one of the main things, because they had no way to be able to comprehensively clean their mouths. And you are right, as, as time begins to move forward and as the public perception hasn't yet caught up with the technology that's available, the status quo as it is at the moment, well, aging is always going to be there. We've always got

• 23:12Chris Williamson?

  older and now we, we will forevermore, was the same as a hundred years ago. People have always died in childbirth, or people have always died from gangrene, or a splinter, or scurvy, or whatever it might be.

• 23:22Speaker 04

  Exactly. That's exactly right. And that's why I think that especially younger people who tend to listen to this kind of show more than older people, really get it. They get that we're going through a scientific transformation and that the future that most people think is coming, that's not going to happen. The future is something quite different. And people who were born today, or people in their twenties and thirties, are going to see radical changes that are far bigger and far more important than the iPhone. Does anyone really care about the next, you know, additional memory in an iPhone? I think we reached a point where a lot of that technology, frankly, is, is being, you know, quite disappointing with the new releases.

• 24:04Chris Williamson?

  I would agree.

• 24:05Speaker 04

  So what's the next big thing for humanity? Well, some of it's artificial intelligence. I just had one of the world's leading AI people visit the lab this morning. Just, that was one of the reasons.

• 24:17Chris Williamson?

  Wow. So that was the reason that we were running half an hour late?

• 24:20Speaker 04

  Tight up a bit.

• 24:20Chris Williamson?

  If Elon Musk's in here, then it's fine. Like, Elon, mate, I'll forgive you. I would like a Tesla Roadster, please, if it's available. But, yeah, it's okay.

• 24:33Speaker 04

  Well, yeah, I, I agree with Elon about a lot of things, but on AI, I think he's wrong. I, I think that we can build AI systems and enough checks that we, we will not be overrun by evil.

• 24:46Chris Williamson?

  Have you read Superintelligence by Nick Bostrom?

• 24:48Speaker 04

  Not yet.

• 24:49Chris Williamson?

  Highly, highly recommended. You know who Nick is? The head of the Future of Humanities Institute.

• 24:56Speaker 04

  Where's that?

• 24:57Chris Williamson?

  Over in London. It's Kerg, I think it's Oxford, Oxford University. He's recently done a podcast with Sam Harris, which is absolutely fantastic. I would recommend checking out. It will be in the show notes below for anyone who wants to to find out what I'm talking about. I don't want to segue on AI, but we've touched on it, so I'm going to do it anyway. The control problem for AI is something that's difficult, I think, not allowing our

• 25:23Chris Williamson?

  creations to get out of hand. Is there a similar concern with regards to developing these tools for longevity that you could

• 25:35Chris Williamson?

  nefarious group could get a hold of the technology and then weaponize it or do something really, really sort of untoward?

• 25:43Speaker 04

  Well, yeah, always. You can turn technology against humanity. I'm not worried about that so much with what I do because even though we have the technology to make mice and probably people age rapidly, it'd be about the slowest way to to damage your enemies. There are much more efficient ways.

• 26:02Chris Williamson?

  Shooting someone in the head has been created as a pretty efficient way to.

• 26:06Speaker 04

  There's that and somewhere in between. You know, we could pretty easily unleash a deadly virus. That wouldn't be too far beyond what we could even do in this lab. Not that we would, but but in terms of making people age prematurely, we can certainly do it. And I could take you downstairs or maybe somewhere I shouldn't say, and there are mice that we can control their aging process forward and backward. So that's doable. Where I think people get uncomfortable with this technology is, so we now understand that there are genes that control how long we live. There's one, for example, called FOCSO, which is turned on in whales and longer-lived animals than us. There are even human variants.

• 26:47Speaker 04

  My children were lucky enough, two of them out of three, to inherit two really good copies of this longevity gene. And so they're probably going to live a lot longer than than my wife and I will. So we know a lot about that. So why does this get weird? Well, now that we can CRISPR engineer babies. What's gonna happen when the world's most intent helicopter parent wants a kid that can live two hundred and twenty? That's probably doable right now. Whether or not we should is another question. Whose job is it to work out whether or not we should? Well, right now, there's a worldwide debate amongst scientists about whether we should come out against it.

• 27:27Speaker 04

  Interestingly, when when human stem cells were first discovered and that you could reprogram cells and clone animals. There was a much greater backlash. You probably remember the the Blair Bush days where there were all these these committees set up and it was banned here in the US, blah, blah, blah.

• 27:48Speaker 04

  We had something just as big happen last year was that the Chinese researcher professor, he

• 27:55Speaker 04

  had a couple of, well, engineered a couple of twins, twin girls who were resistant, going to be resistant to HIV infection, and he engineered engineered those genetically. Now, there was a little bit of upset. A lot of scientists got upset because this was announced without any warning at a scientific conference. There was no oversight. There was no consultation with governments or other scientists. So the shock really took us all by surprise. But there was no major backlash. There hasn't been yet. There hasn't been any outlawing. You certainly don't hear a lot of backlash at the high levels of government, over here in the US at least.

• 28:34Speaker 04

  I think that's healthy. I think that what we've got is a very rational debate. And that we shouldn't just overreact just because something feels weird or isn't, has never been done before. Now, we need to discuss not just the ethics, but is it safe? And I think safety is more important than than ethics, actually.

• 28:53Speaker 04

  And what I mean by that is someone's ethics might be different than yours. I mean, usually I come down on the side of freedom to to do things as long as they're safe and that they're beneficial and there's some consent. But in this case, what's tricky is that your children don't have consent. So that's why I think it's it's a hard one. But what if your child was definitely going to get? Say a dominant genetic disease and there was no way to get around it except um either have new parents

• 29:24Chris Williamson?

  Uh huh.

• 29:24Speaker 04

  Or don't breed um or to uh have an abortion.

• 29:28Chris Williamson?

  What would be an example of a dominant genetic disease?

• 29:31Speaker 04

  Uh so Huntington's, for example, if both parents have Huntington's, you can, or even one, you can have a a child with Huntington's. Um I mean, you can always select the embryo, but maybe you don't wanna kill embryos, so maybe you could create uh an embryo that you go in with this CRISPR editing system and chop out the bad Huntington's gene and create a healthy child. That should be doable.

• 29:56Chris Williamson?

  It's a big ethical question there, isn't it?

• 29:59Speaker 04

  Uh, well, there there is, though i- if you're making people healthier and not suffer. I always say that that's what we humans have always done. That's why we invented aspirin and antibiotics. We're just going into a new era where we can really have a big effect. Because it's not just on one person's life, it's generations forever

• 30:22Chris Williamson?

  Hmm.

• 30:23Speaker 04

  beyond that person.

• 30:24Chris Williamson?

  What's the second order, third order, fourth order effect of this particular decision?

• 30:27Speaker 04

  Yeah.

• 30:28Chris Williamson?

  I guess the the most subtle, the most subtle question is uh between Huntington's disease and a a healthy uh human baby, the line appears to be quite clear uh as what is preferable. But as the fidelity of that becomes, well,

• 30:46Chris Williamson?

  I've got two ginger parents and my dad got bullied at school for being ginger, like, I don't wanna have a ginger child, I, you know, where do we begin to draw the line here? Because in essence, all we're talking about at the lowest or the highest resolution is preference.

• 31:01Speaker 04

  It is, and then it gets really crazy when parents say, I want the smartest kid I can have uh or the best looking kid.

• 31:07Chris Williamson?

  Can we identify the uh contributing factors to that?

• 31:12Speaker 04

  Well, there there was a gene published last year that is thought to contribute to human intelligence and speech that differentiate differentiates us from the chimps. And perhaps having more copies of that gene could make us smarter. We don't know that yet. So I think that that's still in science realm of science fiction. But, you know, looking ahead thirty years from now, you could probably engineer your child to have these traits of certainly height, disease resistance, we can protect against cardiovascular disease. And what about intelligence and longevity? And then we also it gets into a crazy zone where imagine a hundred years from now that

• 31:53Speaker 04

  you can have an army of clones or of people who are robust, who heal better, don't bleed out, they don't get diseases.

• 32:01Chris Williamson?

  Super soldiers.

• 32:02Speaker 04

  Yeah, I mean, this is not beyond possibility in terms of technology today, here in the the second decade of the twenty first century, twenty second century, it's going to be quite something to see. And biology, getting back to the iPhone, I think biology is going to really make a much bigger difference to our lives than any electronic technology.

• 32:22Chris Williamson?

  Wikipedia.

• 32:23Speaker 04

  Yeah.

• 32:24Chris Williamson?

  I do love Wikipedia. Did you listen to Alex Jones on Joe Rogan, the most recent one?

• 32:29Speaker 04

  I did, yeah.

• 32:30Chris Williamson?

  Um, I mean, I don't really even know where to start with that, but the the trans human animal hybrids in the flesh farms, wherever it is, like, is is that the sort of thing that's doable at the moment with current technology?

• 32:44Speaker 04

  Oh, yeah, we we do create chimeric animals in the lab.

• 32:53Chris Williamson?

  Yeah.

• 32:54Speaker 04

  And so that the island of Doctor Mar.

• 32:56Chris Williamson?

  Can you define chimeric, please?

• 32:57Speaker 04

  Well, it's a it's a an organism that's comprised of cells with different genomes. And so it's a it's a mixed organism. And, yeah, we we could do that, but.

• 33:10Speaker 04

  I mean, that, that to me seems highly unethical and even unnecessary.

• 33:14Chris Williamson?

  Well, I, I think everyone would, would agree that that's the case, but it doesn't necessarily stop the technology from occurring. And I suppose the line between how do you, what if you had to do a lot of iterations of Chimera proliferation? And X number of years from then, you would develop this unbelievable new solution to something you've been looking to work on. Does the cost outweigh the, the benefit?

• 33:48Speaker 04

  Right. Well, I think we all, we all have personal views on that. One area that I think is really interesting in this building right here at Harvard Medical School is whether or not you think it's okay to use animal organs for humans. And so one of the reasons we don't use pig livers for transplant is they're full of pig viruses. But George Church and his spin out company are actually removing those viruses, cutting them out of the pig genome so that these livers might be useful. And you might say, well, we, we shouldn't be breeding pigs to, to have transplants. But if we're eating the rest of the animal and throwing away the livers, why not?

• 34:28Chris Williamson?

  That's a very good question. I'd be interested to hear what the listeners think about that particular ethical dilemma about, I suppose the vegans and the vegetarians might be firmly on one side of that already. They don't need, it doesn't matter whether or not the liver's going into someone's body. I think that they've already made their stance on that.

• 34:44Speaker 04

  Yeah, I, I would charge the, the listeners with the following thought. What if it was your mother or your child who needed a liver transplant and there were none available? Would you sacrifice a pig?

• 34:58Chris Williamson?

  That is a difficult question to answer, isn't it? So moving back on to the questions that you get all of the time ringing through the phone. What are the?

• 35:13Chris Williamson?

  What would you say are the foundational strategies that people right now should be looking to incorporate into their lives to improve longevity?

• 35:23Speaker 04

  Right, well, one of the reasons that this field is taking off also is because there are things that people can do right now that we've learned are actually helpful for turning on these longevity genetic pathways. If I could give one piece of advice, only one, and I will give more, but if I could only give one, the most important thing would be eat less. Eating less has been shown for centuries, but also in labs for the last 70, 80 years, to be extremely effective in extending lifespan of everything from yeast cells to worms to flies to mice to monkeys. And if humans don't live longer for fasting and calorie restriction, then we'd be the exception on the planet. And I don't believe that we're an exceptional species, biologically speaking.

• 36:08Speaker 04

  So eat less, what does that mean? Well, nobody knows what the perfect diet is. I get a lot of those questions.

• 36:14Chris Williamson?

  What should I eat?

• 36:15Speaker 04

  What should I eat? Well, what you eat is important, but when you eat and how much you eat are just as important as well. So why don't I give you an example of what I do? You know, I do a fair bit of research and I've come up with my own best practices. So I do intermittent fasting. Now, there are a variety of those, and I think many of your listeners probably know them by name, but there's fast every other day, there's fast two days out of five, there's skip breakfast and perhaps have a late lunch and don't have a late dinner as well. That's the one that I prefer. I find it easier to skip breakfast and have a late lunch than to really go through days of being hungry.

• 36:58Speaker 04

  I can't tolerate it for too long, but I don't mind hunger pains for a few hours. Um. On top of that, uh, I take a drug called metformin, which is prescribed for diabetes, type two diabetes, age associated diabetes, which has two main effects. First of all, obviously it lowers blood glucose. That's what it's prescribed for for for patients. Uh, but it also is is quite rough on people's stomach and I find that it actually stopped me from being hungry.

• 37:28Chris Williamson?

  It curbs the hunger pangs.

• 37:29Speaker 04

  Yeah, it really is effective. And so I have the kind of biology, uh, and so does my son, uh, that we like to eat. We feel hunger more strongly, apparently than other people. We're kind of like labradors of the human world. Uh, but we also gain weight rapidly. We put on muscle, we also gain weight pretty quickly. And so I would, if I was allowed to eat what I wanted to, without a lot of mental power and a little bit of help from metformin, I would be quite an obese person. And and my son, uh, God bless him, he hopefully is not listening to this podcast. He's put on a lot of weight. Uh, he's eleven years old and we're going to the gym. But, uh, you can see that it's it's pretty hard for people without genotype to, uh, keep the weight off. And so.

• 38:09Chris Williamson?

  Body's raring at the, jumping at the bit to get bigger.

• 38:12Speaker 04

  Well, it is, it is. And so he's he's getting strong, but he's also covered in a layer of fat. And so my point is that if I can do it, and you know, I'm I've got a BMI of about twenty one, twenty two. If I can do it, anyone can.

• 38:25Chris Williamson?

  Cause you are genetically predisposed to have a a poor, thin person, uh, body type.

• 38:33Speaker 04

  Yeah, well, you know, my my father, uh, it was prone to obesity, has diabetes and his grandmother, well, my grandmother, his mother had a stroke in her thirties and had type two diabetes. So my, I I have half Ashkenazi Jew genetics coming out of Hungary. Sinclair is not my real family name, it's Sigerty. Uh, those genes are pretty crap when it comes to longevity. And, uh, so we're fighting it. My my father, my son, myself, trying to live at least a normal lifespan.

• 39:01Chris Williamson?

  I understand. So you mentioned that fasting is effective due to calorie restriction. What's the mechanism that that works on?

• 39:09Speaker 04

  Right. So we didn't know how calorie restriction worked until recently. And it's exciting. We understand it. So how does it work? Well, this is partly what we've discovered in my lab, so many others in the world as well, but we can put a little. Brick in the wall for that. We showed that there are longevity genes. They've got the name Sirtuin, actually named after a yeast gene called Sirtu. And that gene controls which genes are switched on and which genes are switched off. It's called a silent information regulator. That's what Sirtu stands for. And this gene really gets back to that clock of aging that I started talking about earlier. It controls which genes should be off to maintain youth.

• 39:53Speaker 04

  But over time, it actually gets distracted and goes to other places to repair broken chromosomes, for example, and ends up causing a yeast cell to lose its identity. It actually loses its sexual identity, becomes sterile, and that's a hallmark of yeast aging. So what that tells us is that there are genes in a yeast cell that control its longevity. Turns out if you give a yeast cell more Sirtu genes or more copies of Sirtu, it'll live longer. Take it away, it'll live shorter. Okay, so that's the fundamental knowledge that you need to understand what I'm about to tell you. Sirtu makes a protein that controls the epigenome of these genes.

• 40:37Speaker 04

  But it doesn't work well unless it has a molecule in the cell called NAD. The long term, the long word for that is nicotinamide adenine dinucleotide. But let's call it NAD.

• 40:50Chris Williamson?

  NAD is much better, yeah.

• 40:51Speaker 04

  Yeah, NAD or NAD, some people call it. It should be called NAD.

• 40:54Chris Williamson?

  Let's not call it NAD.

• 40:55Speaker 04

  Don't call it NAD.

• 40:56Chris Williamson?

  I'm British and NADs are not what I want to be taking.

• 40:59Speaker 04

  No, we, well, you know, some people want larger NADs.

• 41:02Chris Williamson?

  That's true.

• 41:03Speaker 04

  We have, we have NAD boosters in the lab. That's what, that's what my dad takes. So these NAD boosters, the relevance of that is that these Sirtu proteins, these Sirtuins in our body, they don't work well unless they have a lot of NAD in the cell. As we get older and even as yeast cells get older, they lose their NAD. So that by the time you're 50 years old, like me, you have about half the levels of NAD that you had when you were 20. Without the NAD, the Sirtuins are lazy. They don't control the genes of youth well, and they don't repair broken DNA well. And that leads to aging in organisms, we believe, among other things. But that's one of the main causes.

• 41:46Speaker 04

  So what does calorie restriction and fasting have to do with it? By fasting and calorie restricting, we actually boost the levels of NAD in the cell. So that those repair genes and those protectors of the genome, sirtuins, are more active. That's one of the explanations for calorie restriction. There are other genes that control aging. There's one called mTOR, there's one called AMP kinase. And all of these longevity pathways that I'm telling you about are boosted by fasting. And so we think that by being hungry, what you're really doing in a general sense is telling the body, I'm under threat. I might be dead in a month from now. My food supply is running out. I'm gonna hunker down, I'm gonna build a stronger body, I'm gonna survive, I'm gonna

• 42:31Speaker 04

  breed less. Remember, the yeast cells become sterile. We become less fertile if we're starving as well, by the way, especially women. And that's a survival response that we kick into action just by being hungry or by exercising, for that matter.

• 42:45Chris Williamson?

  Is that one of the reasons why bodybuilders, when they diet down for a show and they're at super low body fat, will have trouble with maintaining erections and sex drive and things like that? Is that likely to be the same pathway?

• 42:57Speaker 04

  Well, so I didn't know that for a fact, but it perfectly makes sense that it's a balance between growth and reproduction and hunkering down and surviving. And we call this the disposable soma theory. So this is actually a, a brick, Tom Kirkwood just proposed this back in the 1970s. And the idea is that species as a whole and individuals also are exercising a trade-off between growing fast and reproducing and hunkering down and building a body that lasts a long time. So by stimulating growth and reproduction, so if you take a lot of testosterone, that triggers a lot of growth, take a lot of protein, amino acids, it's great, bodybuilding, you'll repair things better.

• 43:41Speaker 04

  But it's probably at the expense of building a long-lasting body eventually that may run out. So you might wanna pulse between growth and reproduction and then shut it down a little bit by fasting. And so testosterone is one of those molecules that tells the body, grow muscle, which is shut down by being hungry so you'd survive.

• 44:03Chris Williamson?

  So the the actual hunger itself, is it the sensation of being hungry that causes this beneficial effect? Or is it the fact that the blood glucose is low, or is it what's the actual mechanism that it's working on?

• 44:20Speaker 04

  Well, it's actually thought to be both, based on mouse experiments. If you cut back on calories but still fill the stomach with cellulose, that is sufficient to extend lifespan. So part of it is the biochemical response to low calories and low amino acid.

• 44:38Chris Williamson?

  Okay.

• 44:39Speaker 04

  But it's not everything. So the you can be full and you can still get the benefits of low calories.

• 44:49Chris Williamson?

  That's interesting.

• 44:50Speaker 04

  But on the other hand, some people have done the opposite, which is give a lot of calories but simulate hunger. And you can do that by tweaking the brain in ways.

• 45:00Chris Williamson?

  Increasing ghrelin release and stuff like that.

• 45:02Speaker 04

  Exactly. And people can also tweak the hypothalamus, which in itself can extend the lifespan of an animal.

• 45:11Chris Williamson?

  I mean, tweaking the hypothalamus sounds like a terrifying thing to do. It's not taking your car in to get the MRT done or have a service. It's like poking your brain.

• 45:21Speaker 04

  Right, it's changing glucocorticoids, which signal to the body that it's hungry or it needs to grow. And that also extends lifespan.

• 45:29Chris Williamson?

  Does anything not extend lifespan?

• 45:31Speaker 04

  Plenty of things.

• 45:33Chris Williamson?

  I feel like I feel like everything that we've talked about today, I should just live to 120 just by pretending, just testing stuff. I'll open that drawer, I'll see if that drawer extends lifespan, I'll like use the use my left hand to to put that coat on, that'll extend lifespan.

• 45:48Speaker 04

  Well, obviously, we don't we don't read about those studies that failed.

• 45:51Chris Williamson?

  Yes.

• 45:52Speaker 04

  So there's a lot of things in my lab, for example, that never extended lifespan.

• 45:55Chris Williamson?

  Are there any notable examples of that, that you thought, or was there anything that you thought would really was a real winner and then it turned out to not be a winner?

• 46:04Speaker 04

  Well, let's see. So usually we don't embark on a mouse experiment that'll take three or four years without some pretty good science behind it.

• 46:14Speaker 04

  We've tried some plant molecules that didn't extend the lifespan of some species. Gee, let me think.

• 46:22Speaker 04

  We tried some versions of rapamycin, which turned down this mTOR pathway, one of those longevity pathways, and that didn't extend yeast cells very much because we think there was some side effects of toxicity.

• 46:39Speaker 04

  Let's see. Oh, we overexpressed the Sert1 gene, one of these mammalian Sertuins, and that didn't work, and we figured out why. Turns out that in the brain, Sert1 actually has a negative impact in the pituitary. We haven't published this yet, but even though Sert1 made a robust mouse, and it was protected against pretty much all diseases we could give it, diabetes and heart disease, it didn't live longer, and we found out because in the pituitary, it needs to be off rather than on.

• 47:09Chris Williamson?

  So you've got this physically incredibly robust mouse, but it's actually suffering with dementia and it's like super old and super wise?

• 47:17Speaker 04

  Well, what happens with the pituitary is it controls growth hormone. And so by turning it down in the pituitary rather than up, we actually created small mice that lived a long time if we just tweaked it in that part of the body. But by turning it on in the whole animal, that turning it on and gave the mouse a lot of growth hormones, we got a bigger, more robust mouse, but it didn't live longer, unfortunately.

• 47:44Chris Williamson?

  You touched on growth hormone there. I remember watching "Bigger, Stronger, Faster", Chris Bell's documentary a long time ago, where he was talking about recreational steroid use in America, and said that amongst that, one of the commonly used compounds is human growth hormone. The UK is very different to the way that it is out here in terms of getting a prescription from your doctor and all that sort of stuff. One of the places that he went to was an anti-aging convention, and he made a joke about there being loads of old people there walking around, and pretty much every single stall was offering human growth hormone, I think exogenous human growth hormone, as a solution.

• 48:29Chris Williamson?

  What's the truth in that, if there is any?

• 48:33Speaker 04

  Well, I don't think there's any evidence in humans that it extends lifespan growth hormone.

• 48:38Chris Williamson?

  Does it shorten it?

• 48:39Speaker 04

  Well, that's the debate. It's really not known. Anyone who says they know the answer really doesn't doesn't know what they're talking about. But theoretically, it could it could shorten lifespan for a couple of reasons. One is testosterone and growth hormone could make pre-existing tumors grow faster, potentially. But there've been a lot of studies where it's seemingly safe, at least over the course of a year or two. And so I think that, I hate to say this because we all want perfect answers, but the jury's still out about the long-term safety. I think replenishing testosterone and growth hormone to levels that are natural in in young people, I think, should be okay. That's my personal view. Testosterone has been studied quite a lot in the elderly.

• 49:24Speaker 04

  And even though there were some benefits in terms of strength and muscle maintenance, there was apparently no change in mortality. So we need to do more than just raise testosterone, I believe.

• 49:34Chris Williamson?

  Interesting. I guess there's a balance as well between quality and length of of life as well. That you could potentially take something which may shorten your life, but if it only reduces your life by five percent, but doubles your mobility or quality of life, however it may be. I suppose that there's a very big balancing act that you guys constantly need to play when you're looking at these.

• 49:57Speaker 04

  Well, it's not as hard as you might think. By turning on these sirtuin genes and changing mTOR and the same the kinase, the forman pathway, we actually find that we lengthen the health span of the animals. And so what that means is they don't get cancer, heart disease, Alzheimer's, diabetes until much later in their life. That's why we call it the health span. And you know what happens when animals don't get sick? They live longer. That's a nice side effect, right? Animals don't die if they're healthy, same with humans. And so it hasn't been a hard thing to balance. In fact, if you focus on health span, lifespan is a nice byproduct of that.

• 50:37Chris Williamson?

  That's a very good way to look at it. So you've mentioned fasting would appear to be the the Pareto, the eighty twenty of of what we're looking at here for the vast majority of people. It's free. I mean, it's actually better than free. Like, it's it's cheaper than what you're doing at the moment.

• 50:55Chris Williamson?

  What else would you?

• 50:58Chris Williamson?

  As a disclaimer, we are not your doctor. This is not medical advice. Please seek a physician, et cetera, et cetera. Disclaimer, disclaimer. What else do you think is an optimal strategy that some people, if they chose to, would be able to undertake?

• 51:11Speaker 04

  Sure, well, what I do is I, besides intermittent fasting, I also exercise. Exercise is the other thing that raises NAD and boosts these longevity pathways. And we've also known for centuries that this is healthy, right? So we're not discovering anything that new other than what types of exercise seem to activate these longevity pathways the best. And what seems to work best is the high intensity interval training is to get the body stressed. So just as intermittent fasting tricks the body into thinking your food's running out, exercise is tricking the body into thinking I might have to run a marathon. Or, yeah, exactly, there's a saber-toothed tiger in town, or cat. So that's exactly right.

• 51:54Speaker 04

  So the high intensity seems to really stimulate the body's defense networks even more than just a long walk or a steady long run. It's all about varying it, right? The high, the low. So intermittent fasting, it's food, no food. And intensity training is running, stop, running, stop, hypoxia, oxygen, hypoxia. And it's that up and down that seems to work really well. That's why whatever you're doing, do something different and get your body into shock. So the thing to think about is, the concept is called hormesis. But really, the concept of hormesis is just whatever doesn't kill you makes you stronger and longer live, by the way. So keep your body on edge.

• 52:39Chris Williamson?

  It sounds like all of the things that are good for you are really uncomfortable. Or a lot of the things that are good for you.

• 52:46Speaker 04

  Well, that's the sad thing. People say, oh, why is cake taste so, why does it taste so good? And why doesn't sitting on the couch feel good? No, other way around. Why doesn't exercise feel good? And why is sitting on the couch bad for you? I mean, that's exactly the reason is that you've got to put your body in this slight painful experience to get it to react. Otherwise, it becomes complacent and your body just falls apart.

• 53:10Chris Williamson?

  It would be nice if cake extended your life though, wouldn't it? It would be fantastic if that was the case. So what else, what else is it that you're doing?

• 53:17Speaker 04

  What else? Well, so I mentioned Metformin, that's been a recent change.

• 53:21Chris Williamson?

  Is that, some of this, some of this is available without prescription, but I think Metformin is something which you do need a prescription for, is that right?

• 53:30Speaker 04

  In western countries, yeah, in eastern countries less.

• 53:34Chris Williamson?

  Over the counter?

• 53:35Speaker 04

  Well, yeah.

• 53:35Chris Williamson?

  You get everything in Thailand over the counter?

• 53:37Speaker 04

  Yeah, you can, and actually it's smart of them, I think, because they have rampant diabetes like we do, and Metformin is one of the safest drugs in the world. You'll get an upset stomach, it's extremely rare that there's anything more serious than that. It's not perfectly safe, no drug is. But in terms of drugs, this one's pretty safe. It's a derivative of molecule from the French lilac. It's basically a version of a plant molecule. So anyway, so I take Metformin every morning.

• 54:08Speaker 04

  Sometimes I vary it, you know, I'm not strict with everything, but sometimes it's half a gram, sometimes it's a gram. A typical diabetic will take somewhere between a gram and two grams, so it's a bit below that. What else do I do? Let's get this all on the table.

• 54:22Chris Williamson?

  Throw it out there, come on.

• 54:23Speaker 04

  All right, again disclaimer, I'm not recommending it.

• 54:25Chris Williamson?

  The internet is waiting to find out what you do to make yourself live so long.

• 54:29Speaker 04

  Well, no, I don't know if I'm gonna live longer. I'm fifty, people can judge, how am I doing?

• 54:34Chris Williamson?

  You look fantastic, man. Don't listen to, don't listen to the general public.

• 54:38Speaker 04

  Well, see, let me know if I have a gray hair, that's been one thing that's going all right. Anyway, okay, so let's lay it out. So, an NAD booster.

• 54:47Chris Williamson?

  Yep, how much?

• 54:48Speaker 04

  I take a, a gram of an NAD booster every morning. And it's water soluble, so I just take it with a drink, with a coffee, along with the Metformin. I also take a gram of resveratrol, which isn't a strict amount, I actually just shake some powder into a yogurt and mix it up, a few spoons of yogurt. I've also been asked over the internet, on Twitter, that asked, don't you think that that's breaking the fast? It's no longer fasting, I thought you said Sinclair that you'd...

• 55:20Chris Williamson?

  Because you're having a yogurt on the morning.

• 55:21Speaker 04

  Yeah, well, it's not actually a yogurt.

• 55:23Chris Williamson?

  Your petty fallu has ruined the fast.

• 55:26Speaker 04

  I don't regard that as as a lot of calories. I I actually make my own yogurt. It's it's one made out of special bacteria.

• 55:33Chris Williamson?

  Are you considering marketing it? I bet people will buy it. If you if you released Sinclair yogurts.

• 55:38Speaker 04

  It's not mine. It's actually commercially available.

• 55:40Chris Williamson?

  Okay. Where?

• 55:42Speaker 04

  Where? Well, I don't know the people who make it, so this is not an endorsement, but it's called Bravo, and I know it's in America and Europe.

• 55:50Chris Williamson?

  Okay.

• 55:51Speaker 04

  Uh, but it's works out great. Uh, I don't follow the instructions. I just get full cream milk. I get a jar about that big. Uh, and I just pour it all in, shake it up, put it in the oven on on defrost or whatever it is. I think it's it's it's body temperature. Leave it for about twenty four hours and it's beautiful, thick yogurt. And for breakfast, I I take a couple of spoonfuls.

• 56:13Chris Williamson?

  I'm gonna guess that's probably not super calorie dense anyway.

• 56:17Speaker 04

  Probably is. High full fat yogurt.

• 56:20Chris Williamson?

  Full fat milk, though?

• 56:21Speaker 04

  Yeah.

• 56:22Chris Williamson?

  How how much are you having? Like, is it a big bowl?

• 56:24Speaker 04

  Well, I make it in a jar.

• 56:26Chris Williamson?

  How much you eat?

• 56:27Speaker 04

  Two spoonfuls, two or three. It's nothing.

• 56:29Chris Williamson?

  Not breaking the fast. I don't want to say you're breaking the fast.

• 56:31Speaker 04

  Chris, thank you.

• 56:32Chris Williamson?

  They need to leave the they need to leave the room. Don't worry. Um, so what else you doing? What else do you do? You're exercising, you're fasting. You've got your N A D, you've got your resveratrol, you've got your metformin.

• 56:40Speaker 04

  Right.

• 56:41Chris Williamson?

  Is that?

• 56:42Speaker 04

  That's the main thing. I mean, um, my doctor gives gives me a statin because I've had high cholesterol since I was in my twenties. So that's another, you know, thanks Jewish genes, I'm kind of screwed there. Um, I take a uh, still take a baby aspirin a day, even though the.

• 56:57Chris Williamson?

  A baby aspirin?

• 56:58Speaker 04

  Well, it we it's it's eighty one milligrams of aspirin.

• 57:01Chris Williamson?

  Okay, what's that? For blood thinning?

• 57:03Speaker 04

  Right, right. And the the current recommendation in general from the Medical Association, just so we're clear. I I'm not a doctor, but I read the literature, is that if you haven't had a heart attack, maybe, maybe not take it. Uh, I haven't had a heart attack yet, but I'm I'm convinced that it will help with my blood flow.

• 57:24Chris Williamson?

  I thought you were gonna say I'm convinced it's gonna happen soon.

• 57:27Speaker 04

  Gosh, I hope not. That would be a a bad look.

• 57:29Chris Williamson?

  That would be a really bad look, wouldn't it?

• 57:31Speaker 04

  Yeah.

• 57:31Chris Williamson?

  Um, one question that did come out of the Reddit furor, which I think was actually pretty pertinent, was when do you think that people should begin thinking about longevity? Obviously, we think about health our whole lives. Like, we don't just let the kids go loose on a like a bag of sugar. But is there, you know, should people be taking N A D at eighteen years old?

• 57:53Speaker 04

  I love that question because I have new answers to that based on new research, partly in this lab.

• 58:00Chris Williamson?

  Unleash it, unleash it on the world, the internet is waiting.

• 58:03Speaker 04

  Here is something that almost no scientist, let alone in the public, understands. The clock of aging, the epigenetic clock that we measure, and other scientists have published now, just a few months ago, begins even before birth. We are aging constantly.

• 58:20Chris Williamson?

  Oh shit.

• 58:21Speaker 04

  Yep. And it actually tracks with development. Girls who go through puberty early have a faster aging clock.

• 58:30Chris Williamson?

  So they're older?

• 58:31Speaker 04

  They're older, they're literally older. So even though you think you look old, you're actually getting older. And you might age faster than others. It'll show up later in your life, but it's pretty scary, right? So the other thing that we know is that if your mother, while you were in her uterus, ate certain foods, you can be predisposed either to obesity and diabetes or to health and longer life, which is crazy. So you might, one answer could be the earlier the better. Even before you're born, you should be working on this.

• 59:03Chris Williamson?

  N A D is an embryo.

• 59:04Speaker 04

  Yeah, right. If you've got, you know, helicopter parents, they'll genetically engineer you and feed you the right food anyway. But I, the other, the other answer is, this is a really important one, is that in, in animal studies, in mouse studies particularly, the earlier we start, after development, of course, we're not gonna calorie restrict or interfere with these pathways before an animal reaches adulthood, let alone a person. But after adulthood, say twenty-four, twenty-five, equivalent of a mouse, we put them on these regimes of molecules or genes, and that's where you get the biggest bang for your buck, start early.

• 59:45Speaker 04

  If we start midlife, let's say on a fifty-year-old equivalent of a mouse, you get about half the effect of, of when you start early. And that's why, actually, I've been, I started way early compared to my peers, my scientific peers. I started resveratrol when I was in my early thirties. And I probably would have started earlier knowing now. If I knew then what I know now.

• 1:00:08Chris Williamson?

  Well, I guess when you're talking maybe ten, twenty years ago, it's this experimental drug. No one really knows what the effects are and you're just like, fuck it, might make me live longer. I better just take it like that's a big risk to take.

• 1:00:19Speaker 04

  Well, it wasn't that risky. We we had fed it to mice. I knew that it didn't kill them. Uh, and it was in red wine, so I was just taking an overdose of the red wine molecule. But um, I'm prepared to to to die for my science. I've never said that publicly. But I I believe so strongly in what I do and the benefits for humanity. If I had died, I would have been pissed off, but I would have.

• 1:00:42Chris Williamson?

  It would have sucked.

• 1:00:43Speaker 04

  Yeah, but but I I did it knowing that there were risks and everybody who's listening um should know that what I'm saying I do comes with risks, right? I don't know if this gene of this molecule combination with exercise and all this is shortening my lifespan. So far, it's okay. I'm not dead yet. My cardiovascular system and everything else that's been measured comes out pretty healthy. Uh, but there are risks and especially when I was in my thirties. It could have been toxic over twenty years or even toxic for a few months, but I didn't. I wasn't scared of the consequences. I was more scared of not knowing than actually finding out the truth.

• 1:01:19Chris Williamson?

  Well, that's the true uh inquisitiveness and I guess the ex- exploratory nature of someone who is a a scientist at the kind of the cutting edge of this sort of stuff. Um, one of my favorite podcasts that's ever been done is Matthew Walker, the guy who wrote Why We Sleep on Joe Rogan. And I think that the topics that particularly resonate with people are the ones that the um broadest cross section of people can relate to. Everybody sleeps, everybody's aging. And I think that that's one of the reasons why there is such a such an interest in this particular subject. Um, I uh I I I'm was totally unexposed

• 1:02:03Chris Williamson?

  to the whole topic area before your podcast with Joe. And I'm super excited now, knowing about this whole new subdivision of science that I didn't really even know was was this big. I'm super excited to see what happens, the same way as I read Superintelligence by Nick Bostrom. And now I wanna know, I'm super excited to see what happens. I'm terrified. But what might happen with AI? And it's the same for that. Um, do you feel like? A very, in a very fortunate position to be, have your finger in so many different longevity pies.

• 1:02:34Speaker 04

  Yes, there's no question that I wake up every day and most days I pinch myself that I'm in this position.

• 1:02:43Speaker 04

  It hasn't been easy and it's been not just hard work, I don't mind working hard, I love what I do. But it's been, there's been criticism, there's been ups and downs, getting.

• 1:02:53Chris Williamson?

  There was nearly a bankrupt company at one point, wasn't there, and you took a big risk at some point, I think there was a.

• 1:02:58Speaker 04

  Ah, sure, I mean, there's, there's been so many things, so I've helped build about fifteen companies and they all go through strife and running out of money and a lot, most of the money that I make, I pour back into companies. You know, I've made more money than I would ever know what to do with, but what I wanna do with that is, is pour it back in and so my, my wife chews her fingernails because, you know, we're, we're multi, multi-millionaires for about a month until I find a way to get rid of it.

• 1:03:31Chris Williamson?

  The next kill.

• 1:03:32Speaker 04

  I don't want the money, I wanna see that humanity progresses. I wanna see what the future holds, I want us to get to the future faster and that's my way of doing it. But anyway, the adversity, all scientists get criticized if they stick their neck out to do something that's different, whether it's discovering a longevity gene or saying that we could live longer or saying that aging is a disease, which I truly believe it is. All of those things have been tough, but fortunately I, I'm very stubborn and I, I'm not taking my eye off, off the prize in the end, which is that we all get to live, hopefully all of us get to live longer, more productive lives and when we do that, we'll look back at today and think, what were we thinking, why weren't we doing

• 1:04:12Speaker 04

  a Manhattan Project or maybe, maybe I should call it the, a moonshot on this because it's so important. One of the things I truly believe is that we look at all the problems on the planet, it's global warming, there's poverty, there's bankruptcy for countries or at least economic burden of people being sick. All of these are real problems, social security, welfare in, around the world. I think the biggest solution to that, and admittedly I'm somewhat biased, but I do crunch the numbers on this, is if we can solve people's health and make them more productive for another ten years, maybe even longer, but ten years would be enough to save trillions of dollars every year across the planet, even in the US it would be a saving in the tens of trillions of dollars.

• 1:04:57Speaker 04

  This is money that can be put to work, saving the economy and working on other big problems that we need to solve, like the saving the environment, saving species, preventing global warming.

• 1:05:09Chris Williamson?

  Would there be an issue of overpopulation with that?

• 1:05:11Speaker 04

  Yeah, good question. There's no question that if people aren't dying as fast as they would, there will be more people, but it's not as many as you might think. If we stopped everybody dying today, and which we can't do that, but if nobody died again, the rate of population growth would be less than the rate of immigration here in the US, which the government's trying to limit that as well.

• 1:05:34Chris Williamson?

  Yeah.

• 1:05:35Speaker 04

  But it's not as though suddenly there's five times as many people. And the good news is that we're not going to stop aging anytime soon, we're just going to hopefully live another five to ten years. What that means is though that we'll probably plateau around ten billion, maybe up to thirteen billion, but most of that problem is not driven by people living longer, it's driven by the birth rate. And over the last decade, we've seen an extraordinary change in our birth rate as a species, and it's going down all the time and going to plateau. The World Health Organization and the UN have agreed, and Bill Gates has given a wonderful podcast on this, that we're going to plateau out over the next thirty years, and we're not going to be overrun with humans.

• 1:06:19Speaker 04

  In fact, places like Europe and Asia are, especially Japan, are struggling with not enough

• 1:06:25Chris Williamson?

  Need some more humans.

• 1:06:26Speaker 04

  Babies. Exactly, more humans. But what you want to do is also preserve the productivity of the older people. So when we look at a seventy-year-old now, we think that's an old person. Ten years from now, twenty years from now, seventy will be middle aged. Uh, we certainly see that happening already. Look at Tom Cruise, he's, what's he now, in his mid fifties? He's riding motorcycles.

• 1:06:47Chris Williamson?

  Hundred and five and he looks.

• 1:06:48Speaker 04

  Looks great.

• 1:06:49Chris Williamson?

  Fantastic, straight out of Cockpit, Top Gun. And I couldn't agree more. That was the, the question that I wanted to finish on was, um, well, two parts. Firstly, would it be possible to make someone live for a really inordinate amount of time, like a thousand years? Is that possible? Presuming they don't, you know, get shot or one of the easier ways of, of killing someone that we identified earlier on. Is there, is there a realistic upper limit on the amount of time that an organism could live?

• 1:07:18Speaker 04

  Well, we know that there, there isn't. There are immortal organisms on the planet. There are trees that live for thousands of years. There are jellyfish that go on Hydra, these little jellyfish like things. They live for, for seemingly immort- immort- uh, go for immortality. The, the mistake that, that most people have is that they think that there is a biological limit to humans. And they look at human history and they say, looking back in time, there's never been anyone who, as far as we know, has lived beyond a hundred and twenty-two, and even that's doubtful. That's been, that's been challenged.

• 1:07:54Chris Williamson?

  I was in the Guinness Book of World Records, uh, store on Hollywood Boulevard a couple of days ago. And they had the photo of the guy that was a hundred and twenty, that was the oldest certified, I think. But I mean, I'm going to guess that the standards to which you hold your research may be a little bit higher than that, that the Guinness Book of Records does.

• 1:08:15Speaker 04

  Well, whether or not Jean Colme in France lived a hundred and twenty or no, or not, doesn't matter. There are still plenty of people who make it to a hundred and fifteen, a hundred and seventeen. So let's say that's the, the, the current limit, but looking backwards doesn't tell you the, the future when it comes to technology.

• 1:08:34Speaker 04

  When you looked at the Wright Brothers, looking backwards from nineteen oh two doesn't really tell you that we're going to go to the moon within sixty years. So that actually happened. Um, so what I, I think is that there is no biological limit to human lifespan. We are living things. We fix ourselves, we repair ourselves. Uh, we succumb to entropy, no question. We, we lose information over time. But what we've discovered with this reprogramming stuff is that we can regain information that. Is still there. As we get older, we just need to access it. Those genes are still there to make us young. We just need to tell the cell to read the right genes at the right time. And we can reverse aging. And we don't know how many times you can reverse aging.

• 1:09:19Speaker 04

  But it's possible you could. So let me tell you a bit of a story, but it's based on results in the lab. You know how I was telling you we can reprogram neurons to grow again? We can actually use that same virus to infect an entire mouse and turn on these reprogramming genes and get the mouse, we think, to be younger. That's what we're working on. So imagine a future where you could have your genome changed so that you have these reprogramming factors injected. So I'll come along, Chris, today, we can go to my lab if we wanted to. Literally, I could take a vial of the virus, I could get, give you an injection, and it would be compatible with your body, and you would be genetically modified to

• 1:10:00Speaker 04

  be able to be reprogrammed. Now, we've engineered that virus, literally, we have done this, to be turned on by an antibiotic called doxycycline, which you can go get from your doctor.

• 1:10:11Chris Williamson?

  I've been on it for a while. I've been on and off it for the last few years. Yeah, it's used as a, doxycycline is used as an acne drug.

• 1:10:21Speaker 04

  Yes, or antimalarial, or if you have Lyme disease here in the US, it's pretty safe. I mean, you wouldn't want to take a long time.

• 1:10:27Chris Williamson?

  Be careful, you don't accidentally take that when you've got this super gene that's potentially active inside of you.

• 1:10:32Speaker 04

  Well, so here's the thing. We, imagine a future where you now have this virus in your body, and it's switched off, you've, nothing's happening to you, but you start to experience aging. Let's say you're starting to build up cardiovascular disease in your veins, or you're losing your memory. How about you just take antibiotic for a few weeks? Your reprogramming factors come on, your body gets rejuvenated, it finds the youthful information, your nerve cells remember how to be nerve cells again, and you get rejuvenated, you go back another decade. You don't go too far, you stop taking the antibiotic before it causes a tumor or something really bad, and you get reset. And then you wait another 20 years, and...

• 1:11:18Speaker 04

  You turn it back on and you get rejuvenated time and time again. And maybe that's the path to to living for a thousand years. But for the first time in my career, I can actually see how it would be possible to do that.

• 1:11:32Chris Williamson?

  It was just conjecture before, whereas now there's there's an actual mechanism, there's a pathway.

• 1:11:38Speaker 04

  It wasn't even conjecture, it was insanity to think that it was possible. And anyone who would say that we could live a thousand years was considered crazy. And I I'm on record saying that the first person who's born today could live to one hundred and fifty. And I get criticized by a lot of people for saying that because it sounds outrageous. And I don't know if that's true, but I do know that someone who's born today is most likely going to make it to the year. What twenty two, uh twenty at least. What kind of technologies will they have then?

• 1:12:11Chris Williamson?

  You are totally right, and I suppose as well, if, as you've suggested today, aging is a

• 1:12:20Chris Williamson?

  not only something which can be paused at its current point and kind of held where it is, but can also be reversed. It means that as soon as sufficiently sophisticated technology becomes available, everyone who is alive at that time is potentially brought back to wherever they need to be.

• 1:12:38Speaker 04

  Right, and actually, the longer you live, the longer you get to live.

• 1:12:41Chris Williamson?

  Yeah, which is very bizarre. So everybody should be working on not getting shot and not stepping out into open traffic and not eating cake, not sitting on the couch.

• 1:12:52Speaker 04

  Yeah.

• 1:12:52Chris Williamson?

  Because the longer that you live is the potential that you'll get towards being around when we do have this particular solution.

• 1:12:59Speaker 04

  Yeah, I I think the number is every year you live, you get another three months extra of life.

• 1:13:04Chris Williamson?

  That's so crazy.

• 1:13:07Speaker 04

  Yeah, uh it gets kind of weird when you when you get to technology where every year you live, you get another year to live.

• 1:13:14Chris Williamson?

  Wow, that's like the um.

• 1:13:18Chris Williamson?

  It's not Dunbar's number, what's the one that talks about processing power doubling every three years for computers, it's the equivalent but for lifespan?

• 1:13:25Speaker 04

  Yeah, Moore's Law based for lifespan.

• 1:13:26Chris Williamson?

  Moore's Law for human beings?

• 1:13:28Speaker 04

  Yeah.

• 1:13:29Chris Williamson?

  That's fascinating. Well, I mean, I really appreciate your time. I appreciate you kicking Elon out so that I could come and sit down and sit down in your office. Hopefully I'll be back in, you know, five years' time, looking at the same age that I am now and you will be as well. And we can discuss about how far the research has moved from that. If any of the listeners, and I'm sure that there will be, as you've been inundated with requests over the last few years, if they want to do some further reading or look at some things online, have you got any resources or blogs or books that you would recommend?

• 1:14:07Speaker 04

  I do. So I tweet out new discoveries and new things that I'm thinking about and things that other people have discovered. So my Twitter handle is David A Sinclair, no E at the end. And so that's the main way I get daily information out. But I've also poured everything that's in my brain into a book that's coming out later this year in the US. It's coming out in September, early September. It'll be out in the UK and then globally. It's called Lifespan: The Revolutionary Science of Why We Age and Why We Don't Have To. And I'm pretty excited about it because it's going to answer pretty much all of the questions that people have been asking me over the last couple of decades.

• 1:14:50Chris Williamson?

  That's so fascinating. It must feel, I once said this, I did a podcast that was essentially me answering a bunch of questions I get asked all the time. Will you look forward to receiving all of the emails about how much NAD should I be taking, when should I start doing it, is my testosterone out of optimal? And all that you ever need to do is just send them one Amazon link. That's like, that's the panacea answer, right? Just there you go. Read the book, read the book.

• 1:15:15Speaker 04

  Well, that, that, yeah, it's all in the book, plus more. What I want to do with the book is to give readers a front row seat on this world that I'm experiencing every day, which is blowing my mind and making my head spin off. In terms of the input, I try to answer most emails. It gets pretty hard sometimes. I do also do a LinkedIn blog, so also that's a longer format of things that I think about and answers to questions like this. I want to do more Ask Me Anything AMAs on Reddit too, but I look for that.

• 1:15:47Chris Williamson?

  The number of requests, I'm sure that the, the people on Reddit who are currently writing nasty comments about the fact that I can't pronounce the words that they sent me to give to you will be very happy to hear that you will go and do an Ask Me Anything. Guys, if you do want that, don't forget, make sure that you comment below on YouTube or Hassel David, I'm sure that he'll have some, some form of Hassel. Tweet him, tweet him and annoy him and then he'll go back on and he'll do, he'll do another Ask Me Anything. David, it's been, it's been absolutely fantastic. I really appreciate you, you coming on today and having me in your beautiful office. And I'm looking forward to the book coming out, really excited.

• 1:16:23Speaker 04

  Well, thanks, Chris. It's been great to be on here.