AI Just Compressed 160 Years of Aging Research — Here's What They Found | Dr. David Sinclair

You are at the intersection of my absolute fascination with health, which is where it's intersecting right now with AI. I've heard you say that AI is making things possible in human longevity that previously weren't. So, what specifically has AI put on the table that wasn't possible before? Well, so the the big thing is the speed that we can do things. Um we currently have technology that can reverse aging in animals and we'll find out this year if it works in people. But it's it's an expensive technology. It uses genes and we have to introduce genes into the body or the eye in this case. Um that that's potentially hundreds of thousands of dollars to do that. So, what we wanted to do in my lab was democratize this technology. So, how do you do that? Well, AI is helping. We've now screened probably about 8 billion virtual chemicals for one that will reverse aging. So, then instead of introducing genes, which is expensive, we could take a pill or rub it on our hair or our skin. And I asked one of the AI uh sites, how long do you think this would have taken uh in a normal world uh pre-AI? And it estimated it would have uh taken about 160 years for my team to have finished that experiment. And the cost would have been in the many billions of dollars. >> Why is that? Is AI just Is Is it crunching numbers, pattern recognition? What is it that makes AI able to shorten the timeline? Yeah, well, a big one was we we need to thank uh Demis Hassabis for his uh and his team, of course, uh for elucidating the structure of all of the proteins in the body. We didn't have that until uh what was about four or five years ago. And now that we have those structures of those proteins, we can virtually dock billions of molecules into each of one of the each of those proteins and find ones that modulate those proteins either >> Is this based on shape or >> Yeah, mostly and charge. So, we we know the behavior of atoms and small molecules and now we know proteins and proteins are vibrating, so it's a little complicated. >> we know, so one of the things I want to know about AI, is AI getting to the point where it understands the fundamental rules that govern biology or is it just learning all of the patterns in the literature? Oh, it's it's more than in the literature. It's understanding the patterns in biology and how to extrapolate from atoms to molecules to proteins. That's a big jump. We couldn't do that uh more than five years ago. And now AI is really using that. I mean, it it's partly AI, it's partly brute force. Uh just uh mathematics. Uh but on top of that you can add now intelligent agents that can take the results from those screens, as we call them. And we typically get hundreds of thousands of hits, as they're called, And the hit is this shape matches this shape and allows the chemical reaction to transpire. Exactly. And we In this case, what we're doing is is virtually impossible uh at least five years ago it was impossible. And that is that we're trying to find one chemical that does the work of three that we currently have. So, when we reverse aging in a mouse, we give it a cocktail uh down its throat of three chemicals. And in drug development, finding one better chemical can cost hundreds of millions of dollars and years of work. And I'm asking my team and and our collaborators, find one molecule that does what those three do and even better. And then once you found those hundreds of thousands, which ones are most likely to work? Cuz in in the lab, it's not that easy and it's very expensive to order and synthesize thousands and especially hundreds of thousands of molecules. Order meaning online? Like I need to get some of these molecules in the lab so I can get the mouse to eat it. Well, we don't test it on a mouse initially. That would be prohibitively expensive. What do you test it on? Uh cells. And that's also where AI comes in. We've got an AI system we developed. It's machine learning um with a layer of AI that can look at cells from humans that we grow in the lab. And we paint them, so they've got colors and so we can see different shapes and things that are happening inside the cells live or we kill them and stain them. And then the visual we use visualization to say, is that cell from a 92-year-old going back to look more like the 20-year-old cells from a 20-year-old? And we've been working for about three and a half, four years on that. Did you guys have to train your own model or >> we absolutely did. So, we got the cells from these people who are young and old. Yeah, and we trained the model and it took a long time to get that right. >> was just like, this cell young, this cell old, this cell young, this cell old. And then it gets to the point where it's like, you don't have to tell it anything, it just looks at it, it knows the patterns and it says, "Ah, that's an old cell, young cell, whatever." Yeah. Fascinating. Okay, how much so when people talk about um large language models, they're talking about billions of parameters. How many cells did you guys have to feed it in order to get it to be able to discern a cell? Uh we looked at millions um but these days we can actually train very quickly. The the models have gotten better at at learning. Who's doing the underlying models? Uh my lab at Harvard. >> You guys are starting from scratch. Damn. That's why it took a few years, but we're there. We're there now. So, my team used to be just biologists who wrangled a yeast cell and now a mouse, but um I've had to build up my team with uh real uh bioinformatics and AI expertise. Okay, you just gave me the chills. Uh so, here's the thing I'm trying to get people to understand that we're living through the weirdest moment in human history ever and that when we think about the direction of travel and I'll press you on timelines, but I know they're going to be wrong, don't worry about that. I just want people to understand that things are moving faster than they realize. Um I did not realize that individual labs were able to train this from the ground up, which uh is utterly fascinating. But okay, so I'm going to lay out, so I've done a bunch of research on you, obviously. Uh I'm going to lay out what I think are the presuppositions that will make this interview make sense to people. I want them to understand the perceived direction of travel as of today. Of course, it's going to be wrong in fullness of time. I understand that, I'm sure you understand that. But it gives people a direction of travel. So, I'll give you what I think you're saying. If any of this is wrong, let's correct it now so that as we go through the interview, people can understand what you're actually trying to achieve. Okay, so this is me trying to channel what I think you're saying in a very simple, direct uh way. So, biology abides by a set of rules, which means that AI is going to be able to understand it. So, like the laws of physics, we may not know what they are, but there are rules. Those rules are ultimately going to be knowable. So, same thing with biology. Uh AI is ridiculously good at identifying the patterns inherent to these rules, giving AI predictive powers over biology. So, uh if you fold a protein this way, then it will do this. Okay? Uh next is aging is a disease caused by information degradation over time. But cells store the original healthy information in a kind of backup. So far, so good? Yes, uh with a with a little footnote, which is that's the theory that my lab works on that we came up with. It's not universally agreed upon that there that it there there is a backup copy, but it has to be there cuz we use it every day to achieve what we do in the lab. Okay. Uh so, that one may be a little bit controversial, but this is the point of science is we're going to find out. Okay. So, next, any disease tied to a breakdown in information integrity, theoretically, can be effectively treated if you can get the cell to start reading this That's correct. >> Okay. Therefore, AI is going to dramatically accelerate the effective treatment of many, if not all, information-related diseases, including aging. Um I would say that's as close to a fact as we could get right now. Th- This is the the presuppositions that you're operating on. So, presumably, in time some of this will end up being true, some of this will need to be modified, whatever. But these are the things that give you the courage and momentum to go down this path. Yes, and and it even if some of it isn't 100% true, we're still going to achieve the goal cuz we can do it. We're just trying to figure out how it how the heck it's working cuz we're getting results that are nearly unbelievable. And we have to figure out, how's that possible? So, what the nuances will argue probably for the next 50 years, but it doesn't change the fact that we're doing it. Yeah, that makes sense to me. I have a I'm haunted by and I can't remember if it was Max Planck who said it, but whoever said the quote that science advances not one insight at a time, but one funeral at a time. That winds me up. It drives me absolutely crazy that people cannot go, "Well, there's obviously something I don't understand. I'll figure it out." This is the whole point of the scientific method. In business, I literally teach this. I call it the physics of progress. The physics of progress is, make your best guess, you're going to be wrong to some degree, run the experiments, figure out in what way you are wrong, adapt, get a little bit better, and then you just run that cycle over and over and over. So, I presume that's what you're doing as you march down this path. Yes? Yes, with the scientific method, which is fail, fail, fail, and then something works. Okay. So, we know what we believe and what we're pursuing. It's the things that I just ran through. What would be the falsification? How would we know if we're like, oh, we just proved that this doesn't work? Well, we we've been doing those experiments trying to disprove our theory. That's what we do as scientists. Very What's the what would be the kill shot though? There are two main tests. One is if we degrade the information in the cell in an animal for instance or take a mouse and the mouse gets sick and dies, but it doesn't get old. Then that's not aging. That's just sick. But we did that experiment and the mouse got old. Mhm. And we published in 2023 that information loss is a cause of aging in mammals, in us. Then the next test is can you reverse that process? Can you bring back the information like my hypothesis says we should be able to do even if we don't know where it's stored. Um and in 2020 on the cover of Nature magazine, which is as as good as you can get as a scientist, we published that we could do that, that we could get back that information somehow using three genes that embryos usually use to reset their own age from their parents' age. And so those if they had failed, if we couldn't reset age, if we couldn't age a mouse forwards, uh then okay, we'll move on. We'll do something else. But the fact is now time that in my lab we can drive aging in either direction at will using the technologies that we've developed and it's only going to get better. Okay, in mice? In mice and we've done it in monkeys. Um we've cured As effectively or is that more complicated? Um it's actually not that not more complicated uh in a monkey. If you want to get into the details, it's there's a there's a membrane in the monkey that the mouse doesn't have that might have inhibited the genes getting into the back of the eye, the retina. But it worked fine and the monkeys they got their electrical signals back in their optic nerve and we believe that that is good enough signal to go into humans to treat blindness, couple of diseases in humans. And if all goes well, we'll get ready to start the trial. We'll get back to the show in a second, but first let me brag about someone on my team. G, one of our guys here at Impact Theory, just ran his first marathon. Was very impressive. He finished in 3 hours and 31 minutes. >> [music] >> G, if you're listening, I am super proud of you, man. And Ketone-IQ is what fueled him through all of his training and the race itself. Now, think about that. A marathon is 26.2 [music] miles of sustained output. Your brain does a version of that every [music] single day. That's where Ketone-IQ comes in. It was originally developed through a $6 million Department of Defense contract to support elite cognitive performance. Ketones deliver clean, stimulant-free energy directly to your brain. They cross the blood-brain barrier and fuel your neurons at the cellular level. No sugar, no crash, just calm, sustained mental clarity. >> [music] >> I take half a shot when the afternoon slump hits or I have something important coming up and I need to power through and I'm telling you this stuff works. If you're ready to fuel your brain properly, visit ketone.com/impact for 30% off your subscription >> [music] >> or visit your local Target to get your first shot for free. And now, let's get back to the show. Okay, uh so membrane was a concern, but just didn't end up in practice being a problem. Right. Um but the fact that it worked in monkeys where a lot of things in mice don't translate into primates was a big deal. And so that raised my confidence level from 50% to about 80-90%. >> Okay, but the big question mark right now is you're reaching into a black box that we don't quite understand why it's working because you're you know the effect is that using those three chemicals? The genes? Genes? >> Well, we we got we've got three genes and three chemicals. Okay. Um I don't know why it's three, but that's just what turned out. Sure. The three genes have a name. Um Oct4, Sox2, Klf4, OSK we call them. And they were we can talk about how they were found, but essentially those three genes now we mimic those with three chemicals. And hopefully, as we discussed, get down to one pill that we can take. Okay, we'll get to the pill in a second, but uh so we administer the genes and the chemicals which we don't have to get too specific. I think people will uh not be able to track, but we've got those things. We get them into the system somehow, some way, whether it's injecting, pill later, whatever, whatever, but we get them into the system where they need to be. >> Yep. But we don't know exactly how we're then able to get the cell to de-age. I don't know if we're comfortable with that word. But we know that it happens. And so your best guess is that there is somewhere in there the storage of the youthful, healthy cell, like a backup. Mhm. And that is somehow getting the cell to reread off of that versus the whoo, I might be jumping ahead here, but the methylated cell that's sort of gotten the scratches on the CD of the DNA, if you will. Right. Over time, which is causing it to again, I worry about getting too far ahead, but I'm going to say it anyway, the cells begin to dedifferentiate. So an eye cell stops being just an eye cell, maybe it's a little bit of a skin cell or a brain cell, whatever. And so it starts getting confused. >> Yeah. Uh How did we do so far? Uh brilliantly. Um yeah, I couldn't have said it better myself. >> You can and have, but that's very generous. Uh okay, but we now, at least hopefully people following along at home, understand what we're trying to do when we say that we want to take this we want to take a view of aging that it is an information integrity problem. That there is something akin to a backup copy of what the cell should look like. But aging is basically, oh, we stopped checking the original work and we just start going off of like the repaired house, if you will. And it's like, well, the repair starts to get weird unto itself. And so now it's we're not replicating properly. Okay, you guys have a mechanism to somehow, some way get it to build as if it were a young cell again. Well, build isn't the right word. It's to read the right genes at the right time. >> you say build isn't the right word? Well, when you reinstall software, I guess you could call that a build, but I don't mean it's not physically building. >> is being built, which is why I think of it as building. Oh, well, you're you're putting together two theories. My theory is that the cell and aging is information and the old theory is that the cells just break down, wear out. And so you're thinking rebuilding that repair, right? Restore and so >> Interesting. The way I'm thinking of it, which is probably um messy because I've not thought about it like you have, uh goes something like this. I I'm not playing a song. I'm building a house. And so the cell is physical. So when the DNA gets uh we're going to have to explain methylation. Um do you want to give people a quick primer on exactly what is breaking down? Like what methylation is? The tight winding, all that. >> Yeah. Uh and then we can get back to why I say building. Sure. And I I think where you're going is that when we restore the information, the cell can now rebuild itself in a youthful way. >> when it builds the next one, will build it better and it will be a truly differentiated cell and a truly differentiated eye cell. >> the health and the youth of nerve cells in the eye and elsewhere that don't divide. The cell itself gets healthy. Doesn't need to even grow. It can just reinstall the software. Then it makes new proteins, makes new lipids, makes new uh come out >> were cells that didn't divide. So there are cells that don't divide, full stop. Oh yeah, your heart, your brain. Mostly that's the same cells you had when you were a teenager. >> wild. Okay, didn't know that. Thank you. Yeah. Okay, so sorry. Uh explain to people methylation just real fast. Yep. All right, so that we've got 6 ft of DNA in our cells. Every cell gets wrapped up. Um and there are 20,000 genes, but not every gene gets turned on in every cell. The cell wouldn't function. So we need a certain set, let's say 10,000 nerves nerve genes and then a different set for skins skin genes. So it's like a piano. You got lots of keys. Every piano has the same set of keys, but how you play them makes the difference to the music. The cell works the same way. Same genes, play them differently, you get different cell types, you get a different >> What is the play just to not be analogy? Is it um the creation of proteins? Mostly. Mostly. Not all genes make proteins. Some of them make other things like RNA. Um but yes, mostly it's we're talking about those proteins that become enzymes that do the work of living and repairing. Okay, so we are even in a cell that isn't dividing. So I was wrong about necessarily what is being built. But the thing that we're fixing is the building mechanism itself. So we're building enzymes, which by the I had to look all this stuff up. Uh enzymes like do a thing. They like move around. They're machines, for sure. They're really super interesting machines. They all there's tens of thousands different ones. Yeah, and they do cool stuff. It's so wild. >> Including reading the genes themselves. So the DNA is a is a string of chemicals, right? And the cell has to open up the DNA strand. It's double-stranded. It's a helix, like a think of it like a um a spiral staircase. It looks like that. But to read it, you have to open up the stairs. Each stair splits in half and the cell can read that half of the of the stair. And a gene is about a thousand or more of those steps. It'll read that and it and the a set of three of those steps determines which amino acid goes next in the protein. There's a what's called a start set start codon and it always starts with the amino uh methionine. So, every protein has a methionine almost every protein has a methionine. But, what comes next is dependent on those three steps in the rung of that staircase. Or, in this case, the letters on the DNA ATC or G. Now, that's a gene, right? A thousand of those steps in that chemical. And, there are 20,000 sets of those that are all encoding proteins at the amino acid level. That's your blueprint. But, the problem with aging is the cell forgets which genes to read. It actually turns off some genes and for the most part turns on other genes and now instead of having skin genes turned on it's some skin genes and some nerve cell genes and kidney genes start to look more like liver genes that are coming on. And, that inability to read the right music of the cell I think is the major reason why we get sick and get old. And, that that's reversible. These methyls are little chemicals that get attached to the rungs of the staircase the the steps. And, if you have lots of them on the steps the cell doesn't read the gene anymore. Shuts it down and you don't make protein. So, that's why a nerve cell isn't turning on skin cells genes because they've got a lot of these methyl chemicals on the ladder uh on the steps. They basically say to stop reading or only read this. Yeah, don't read this one. Go and read the one you need to go read. But, those methyls including more complicated structures larger structures um are what determines when we're developing in an embryo go over here and make some skin, but go over here in the skull and make some more brain cells. Okay, and the methylation has to be redone every time a cell divides or takes damage? Yes, um every time a cell divides you should be getting an identical methylation pattern Mhm. between daughter and the parent cell. Uh and there are copying mechanisms we understand how that works. Uh it changes during development of course cuz we're starting from one cell that has to become hundreds of different types. The problem is as we get older through things that we believe are uh largely due to cell damage and stress in the cell those chemicals on the ladder on the stairs they get misplaced. They get taken off where they shouldn't be and put on where they shouldn't be. Mhm. And, now the cell doesn't know what to do. It's reading the wrong music and uh it's a complete disaster. We get gray hair, we get wrinkled skin, we get disease, we die. Do you have a hypothesis as to what is making the methylation be imperfectly um replicated? We do. Um and the the history's not well known. Um when I came to the United States you probably noticed I don't have a strong American accent. Not yet. Um I went to MIT and the goal was to figure out why the yeast cells that make things like beer Vegemite uh which I really like. Tom, I'm going to get you some. The the uh the yeast cells they're microscopic, but they have chromosomes just like we do. And, so I I figured if we if we can't figure it out for yeast cells we'll never figure it out for humans. So, for 4 years I worked under the tutelage of a professor who deserves a lot of credit, Lenny Guarente. And, we worked together he and I and a a team. And, we put out a paper he and I just on on my first big paper in my life um the cause of aging in yeast cells. And, that was the blueprint excuse the pun for the rest of my career including the information theory of aging which we're talking about now. And, in that I said that what's largely changing these patterns of gene expression what we just called the process of aging is that proteins that should be turning genes on and off we call them regulators protein regulators of genes. They get distracted by doing other things. And, there's one set of enzymes and proteins that I've worked on my whole career that came from these studies called sirtuins um based on the gene called Sir2 in yeast. Sirtuins they actually go to the DNA and they tell the cell shut this gene off. They they see the methyls. They see those chemicals. And, those chemicals are really simple by the way. They're just a hydro uh carbon with three hydrogens. These methyls are recognized by the sirtuins. They And, these proteins go in and help shut off the gene and stop the cell from accidentally reading it. They bundle it up. They actually bundle up the DNA like a little package. Mhm. Um versus a big loop of open DNA that gets read. So, it's a bundling sirtuin. And, there are a few breakthroughs. One was that uh the sirtuins get distracted and one of the major distractions that they have is broken chromosomes. They hate broken chromosomes. Yeast cells and our cells they can die if they don't repair a broken chromosome. Mhm. Or, in our case you get you can get cancer. So, a cell panics when there's a even one break on a chromosome. And, it often happens when cells are dividing and they're trying to separate the chromosomes. They get caught, tangled up, break. Now, you're screwed if you don't fix it. So, the sirtuins have an have two roles. One is to control these methyl patterns and genes. But, they also go repair DNA. And, they'll prioritize repairing the DNA. >> They do. Otherwise, there's no cell. Okay, and so if you're doing something that breaks your DNA frequently you're going to age fast. Presumably cuz it's going to be so distracted repairing that that it's not doing its job with the methylation. Yes, and remember how I said there was a test of the theory which was if we cause aging Mhm. do we get an old mouse? So, you just go up their DNA basically to cause the sirtuins to run over to have to fix it. Well, we did I wouldn't use the word F. Because we were very precise. We were surgical about it. We we found an enzyme that is in a slime mold found in the forests around here. And, there turns out there's an there's an enzyme that cuts DNA rarely in mouse and human cells. Mhm. Um Yeah. a dozen or so sites maybe couple of dozen. But, not thousands. And, cuz you'd kill the mouse. So, we surgically uh inserted that slime mold DNA into the mouse itself at the stem cell stage and then we turn that stem cell into a mouse which is standard procedure for students these days in my lab. Damn. And, uh that mouse now we could turn on this cutting enzyme from the slime mold and surgically create a few of these broken chromosomes. Uh not a lot not enough to kill the mouse, but it just enough to distract the sirtuins from their normal job make the cells panic and see what would happen. And, we did that for 3 weeks in these young mice and nothing happened. It's like oh goodness the the experiment's not going to work. Nothing happened. But, then I thought you know when you get an X-ray you get a lot of broken DNA, but you don't feel it. So, let's just wait to see what happens. And, I went to Australia uh and this was the year 2012. And, I got a photo on my old iPhone. And, it was a photo of a sick mouse and the text was should we kill the mouse cuz it's looking really sick. And, I said tell me which is this mouse. They said oh that's that's the one we treated with the slime mold cutting enzyme. Mhm. And, I said that's that's not a sick mouse. That's an old mouse right there. So, that was the first evidence that by distracting sirtuins to broken chromosomes it leads to an acceleration of aging. We published that it took another decade to publish. And, this was this uh big paper I mentioned was in the um in the journal Cell which again is pretty hard to get into. Mhm. And, this was the one that said uh that the change in information loss of information was the cause of uh aging in mammals. What's the difference in phenotypical expression between something that's naturally old and something that ages due to the breaking of the DNA? Nothing. Literally nothing you wouldn't be able to tell. Right. That was the coolest part. Except that they were 50% older and we can measure and we did. We measured the methyls across the chromosomes. And, we can use those changes as a clock. Um and in fact you you probably know you can get a DNA methylation clock done these days commercially. So, we did did it on the mice and the mice were 50% older those methyl changes Mhm. were the same as an old mouse just happening 50% faster. Yeah. Okay, wild. So, that sets us up well for understanding the thing that we're chasing. Now one thing I've heard you say about AI is just the timeline speed up that we get here. So, what is the where are you injecting AI into this process? Is it simulating biology and simulating cells and just like running thousands of experiments in the amount of time that we can normally run one or where's the real advantage? Uh it's simulating experiments. So, normally we would in the case of finding chemicals have to get make the chemicals which can take weeks for each one. Imagine trying to do 7 billion or 8 billion. Uh so, we don't have to make them anymore. We can actually we're now at the point and this is this is new news I think everyone would be interested in hearing. We started doing 8 billion which we thought 2 years ago mind-blowing 8 billion. Normally, a pharmaceutical company might screen couple of million, right? That's physically. We can now do an infinite number of molecules. We believe that we're going to cover all possible chemicals. Woah. Which is an orders of magnitude bigger than what we've been doing. And, that's that's only happened in the last year that we could do that. Um but, what's what's speeding it up is the ability to turn physical world into synthetic virtual and instead of it taking a year to figure something out that it can be milliseconds in some cases. And what's the most complex thing we can simulate? Is it the cell? Can we simulate a liver? Like No, biology is so much more complicated than most engineers understand. Um we're we still probably only know about 3% of biology. So trying to trying to model it is pretty hard. And then the complexity I mentioned that it took all of DeepMind and uh and those guys until recently to figure out how to just model a protein of a thousand amino acids. Even 20 amino acids was a challenge. Trying to model a cell is going to take a lot more work. It's not impossible cuz you will make assumptions, but there's there's no way in my lifetime that I I believe that a cell can be modeled from the ground up looking at every molecule. Really? In your lifetime? Right? And I'm an optimistic guy. >> I was going to say you don't plan to die too early. That's wild. So you're saying we're what more than 50 years away? That's crazy. To model a cell with every molecule? No, I mean you can make assumptions. You can say okay generally these proteins are around in this cell and these proteins are around in that cell, but to say to if if you're right, well if if they can do that what they should be able to do one day is to take an egg Mhm. and the genome and what we call the epigenome those methyl marks and predict what the human looks like. Yes. We'll get back to the show in a second, but first let's talk about the thing your business just can't survive without. I go live three days a week at 7:00 a.m. [music] And every single morning you guys show up. You're there, ready, and if my connection drops in the middle of that live stream, the moment's gone forever. You do not get a second chance [music] with live content. When you're a digital media company, your internet isn't a utility. It's your entire operation. Every live stream, every interview, every piece of content flows through that connection. One drop and I lose you. I lose the momentum and I lose the trust that I've spent years building with this community. And I know a lot of you are in the same position. Your business depends on staying connected. That's why I trust AT&T Business. They're built for business owners who cannot afford downtime. Reliable connectivity, simple setup, and the kind of dependability that helps you stop worrying about your infrastructure and start focusing on your people. [music] Impact Theory is powered by AT&T Business. Built to work. Get AT&T Business at business.att.com. And now let's get back to the show. I suppose this is where I confess my base assumptions. My base assumption is that our current um quest for intelligence shows no signs of asymptoting. So it's going to keep getting better. And so as we come up with more efficient algorithms, as we're able to make bigger and bigger data centers, that AI will get smarter and smarter. Uh if you can believe that in very narrow ways we've had AI achieve something like 147 IQ uh and that's I mean what are we you know 50 years into like real AI development. So it's like in the next 50 years given where we're at, no way. Like you will uh this is going to be ignorant and wrong, but it will give people certainly how I view this. Um 10 years? I can't fathom a universe in which 10 years we don't hit artificial general intelligence. Ray Kurzweil has been right with his predictions I think 87% of the time. Uh says 2030 that's four years for anybody keeping score. He says we'll hit AGI. The question becomes is artificial general intelligence given that at that point it will be able to improve itself uh is artificial super intelligence four years and one day? Like or does it take longer? But I don't I cannot fathom a universe in which we don't hit artificial super intelligence in 50 years. I agree. But you just said that we won't be able to map a cell. And so what I'm saying is you'll get into a an upward spiral of intelligence where we can't imagine doing it now because being locked into in my case very low IQ and your case better, but like as you start pushing this into the I mean what does uh the smartest guy ever clocked I think is like 225 IQ or something, but I've seen his tweets. I don't buy it. Uh so 250, 300, 400, 500, a thousand IQ like what does that start looking like? Well, it's not IQ that's the problem. Mhm. >> The the problem is the compute. Now maybe with quantum computing we're going to get there. But using traditional computers to model the interactions in a cell even for a millisecond would be more calculations than I've ever been performed in a computer to this point. Yes. Um so you don't believe you think that um advancements in computation are going to stall out. Um even if they don't it probably would take more molecules than exist in the universe to without quantum computing to calculate what happens in a cell within 1 second. Mhm. It's that complex. It's it it's mind-boggling how complex a cell is. Um so we can model one molecule hitting another and we can even model uh I can imagine modeling uh a million molecules. But molecule modeling an entire cell with the quantum effects that happen a lot of it's unknowable without going in and disturbing it as well. So that's another issue. Mhm. But what what I'm not saying is that we can't model a cell. I think that we will be able to model a cell and I know very smart people who are doing that or trying to do that right now. It's just that we don't know enough about biology yet to make an absolute model from the ground up. There's a lot of assumptions. We know the fundamentals. We know that there's DNA and these methyls and we know that proteins get folded. Uh but I can tell you from work in my lab there's a whole area of biology that we've been missing that uh will hopefully allow us to figure out where this backup copy is. And without knowing that stuff >> uh describe the black box into which you're appearing right now. What do you mean? There's a whole area of biology that we don't know. Uh well one of one of the problems with science is we don't know what we don't know usually. And that's the tough part. But one of the big questions in biology right now is how does a cell de-age? I I do like that word. And we we know that it de-ages not just from work in my lab and others like mine. But we know that you can take a skin cell. I could take your skin cell. I could take the DNA out of your cell. It's going to be old. Not too old. >> How dare you? It's going to be older than a baby. And I could inject that into an into a an egg uh and theoretically um actually it's not even theoretical. I could turn that into a sperm and turn it into an egg. Now I could fertilize you and make a clone out of you. This has been done with with simpler organisms, but we can do it with humans uh eventually. I think that's how IVF one day may be done if people want to [clears throat] have children if they don't produce eggs. We can Chinese doctor that went to jail. I forget his name, but follow him on Twitter. Shout out. Uh he cloned humans, right? No, he genetically modified a baby. To be resistant to HIV. Um but his goal is to and and he's he's doing this offshore from US of course, but there are there is the technology to do that, but let's just say >> haven't cloned humans. That's the punchline. No, no, but we've cloned monkeys, okay? So let's just stick to monkeys so it's not controversial. Although even that's controversial. Uh how about we talk about Barbra Streisand's dogs? She's cloned those. Or Tom Brady who recently got his Okay. All right, so we can do that. That was done with old DNA. The DNA gets reset. Mhm. The information can be reset in that cell. The other thing we know is that if you have parents who are 30 years old and they have a baby, for the first week of life that embryo is 30 years old. What? Yeah, we we're not always young when we're alive. Babies would be born old if there wasn't a reset switch. Uh-huh. So So wait, at what point are you saying this is like we know this that embryos are >> We've measured it, yeah. Wild. Right? It's a fairly new discovery which is why it's shocking. But it will be known one day pretty well. >> point post um conception Exactly. Day seven to day nine. We know that. Woah. And the baby goes back to being age zero again. Woah. All of us. We were once the age of our parents. So I was my parents were at about 30. I was 30 years old twice in my life. When I was conceived and when I hit 30. That is wild. Okay, didn't know that. New info. And then the same the same mechanisms we believe same mechanisms are what we're using to reset the age of human tissue and monkeys and hopefully Okay, so we got under this because there's certain things we don't know. You're saying we don't know why those reset. We don't know how it resets. How does the cell know what it was 30 years ago? And does this feel like it falls into a category of the unknowable or just we don't know yet? Um we have a pretty good idea in my lab, but we haven't told the world yet. Okay. Um I I do text my student often and walk into the lab and say "Have you figured it out? Have you proven it yet?" Um but what I'm doing is experiments. >> needs to hack your phone. I know they shouldn't, but >> [laughter] >> you probably could with your team out there. Um but yeah, so so Chris Petty deserves great credit. His PhD is on finding what we call the observer which is what Claude Shannon in at MIT in the 1940s called the backup copy. >> Mhm. Um So, what we imagine and are testing is whether there are structures that get laid down when we're very young during our youth that can be accessed later in time in a 60-year-old, 70-year-old to reset the age. Not We don't want to go back to zero. That was the breakthrough we had in 2020. You don't want to go back to zero. I mean, first of all, who wants to do high school again? But, you probably get cancer. So, we don't do that. So, we figured out a way of using those three genes, OSK, to go back 75, 80% and stop. >> Mhm. How does that happen? We think there are little messages with new biology, structures, chemicals that are new to biology that AI may not have figured out or will not figure out easily. Maybe they would. But, that's where we're at now. If we probably in the next few months we'll know if we're right. And uh I've been saying that for about a year now, but we're close. We One One way you do this as scientists is we look for necessity and sufficiency. All right. Necessity from an evolutionary standpoint? No, from a genetic standpoint. What we do as scientists, geneticist, is if we change something Mhm. Let's say if we knock out a gene is that gene necessary for the reversal of aging? >> Mhm. Is that process necessary? And then if we force it to turn on and now we we trigger that event, is that sufficient in itself to to make the change? And when you get necessary and sufficiency satisfied you're really onto something. And it was similar with that mouse, right? We knew that uh it was necessary uh that uh these methylation changes could rewind rewind rewind aging. But, also we knew that it was sufficient to change those methyl chemicals to cause aging. And that's why I'm so certain that the information theory of of aging is correct. >> Mhm. Okay. Uh this brings me back to something I asked you earlier, but I want to push on it a little bit. So, when you interface with AI I've always said if AI can come to understand the fundamental laws of physics it will be able to make novel breakthroughs and all bets are off, technological singularity, the world is unknowable to us. Um as you're approaching it, has AI made any novel discoveries, novel insights that aren't already in the literature, or is it just doing a really good job of recognizing patterns in like what we already know about a cell? We in my lab collaborated with another group out of Stanford who developed an agentic system with multiple agents, about a dozen agents that did different things, and we fed it our data. Interestingly, it's the data that mapped those chemicals on the DNA that change with time. And we did mouse. We've looked at tissues from mouse at very young age, middle age uh about our age and then even older equivalent. And [snorts] uh the the what happened was the the agents went to work and and about a month later and there were some iterations, right? It probably didn't take a month, but we got the data back from this group we were collaborating with at Stanford out of Stanford. And what was incredible was it didn't just come up with validating what the field, the smartest people in my field, had done over the last 10 years. Which which by the way would have been oh yes, you can make a clock out of DNA methylation using these parameters and this you know, Markov modeling and and uh you know, all all sorts of of what was already known in the literature, which is what I was expecting. What happened was it came back and said, "Hey, did you guys ever think of this before?" And came up with a completely new way of looking at the data and making a new model to predict biological age out of the data we gave it. Not only that it it proved the data, it did the statistics, it wrote the paper up for us and presented us with the finished product. Which sucked cuz we want to be co-authors, too. So, we changed a few words, but now I'm a co-author with an AI system. Damn. That we have It's up online, but it's not published yet. But, you can you can find it on bioRxiv. >> Mhm. If you know, if you do Sinclair agentic uh biological clock you'll find it. >> holy this is just had a novel insight and how fast are or It It was a holy because I thought that my job was not at stake. Mhm. The arrogance was I've got all this knowledge and experience and gut feeling and I'm really creative. But, here I'm seeing the beginnings of creativity that can be super creativity in the future. And I I think most people who are not like us at the forefront of technology like discussions with my father who's 86 AI can never be creative. That's just human arrogance. They definitely are already creative and it'll only get better. Yeah, that's uh that's encouraging in terms of its capabilities if it's actually able to understand the fundamental rule set and then say, "Hey, what about this?" Okay, so we You guys have created in your lab a um model that is able to actually gain real creative insights based on what it understands about biology and all the cells that it's seen and all of that. So, where is this pointing? If you don't have conviction that we'll be able to simulate a cell in your lifetime is it that you don't think we require the understanding or the sophistication in order to profoundly de-age the body because the body is the very complex system that you don't think that we can fully understand. But, yet you seem optimistic that we'll be able to influence these incredibly complicated processes in a way that is both knowable, so we can do it repeatedly um and advantageous. For age reversal? >> Yes. Absolutely. We're doing it already. There's no question about that. >> Why? We don't need to know every molecule in a cell. >> as long as we understand how to manipulate the output, nothing else matters. And knowing why it works is the hard part. Manipulating it to give us a predictable outcome is hard, for sure, but far easier Oh, yeah. >> than the simulation. >> Yeah, yeah. Yeah, my students, I mean, they're in their 20s, they have regular tools, they can do it. You I could set you up in the lab, you could do it. It's not that difficult now that we have this hypothesis that appears to be true. In the same way, I often refer to the Wright brothers cuz this this is our Wright brothers moment for humanity when it comes to aging. And there are skeptics like in 1904 people were saying, in fact, the New York Times published that it would take a million years or more to figure out how to fly. Uh and then it it was like 3 weeks later Wright brothers. That's how I feel when you say that a cell won't be replicated, but you know, it's all right. Yeah. Uh well, they we don't need to know and we still don't know how every molecule in an airplane functions. Yeah, fair. We don't need to model that. We We can make assumptions, we can make generalizations about wind flow and wing structure and metals. Same with the cell. But, you still need to know what's the metal? Mhm. What's the wind? How does How does air work? And there's still a few missing pieces when it comes to biology to be able to simulate an entire cell. But, when it comes to aging, I think the big breakthrough was understanding that aging is information and that it can be reset. >> So, how far are you going to be able to push that though? So, I'll give up, doesn't matter, not going to be able to simulate a cell, doesn't seem like it's relevant, to be honest. So, now we've got uh we're showing great signs that we can improve eyes. Um I want to feel as good as I did when I was 25. I want to look as good as I did when I was 25. Like, how realistic is it that we can go in and influence multiple systems in the body in coordination with each other and not end up with whatever catastrophe looks like. So, I imagine the catastrophic fail here, which you've already mentioned, is cancer. That would be one catastrophic fail state where you go back too far and it just all hell breaks loose or um getting into some sort of decoherence where it's like uh we are telling the cell to move in a direction and we can't stop it or whatever. And so, it just basically becomes a pluripotent mess. Um so, how far can we take this? Yeah. Well, pluripotent is a good word. We'll just explain it that that's a cell that can become any other cell type, so age zero. Uh and that won the Nobel Prize. Uh Shinya Yamanaka deserved the Nobel Prize for figuring out that using his Yamanaka genes, of which we use a subset can take cells back to being pluripotent. It's incredible. And that's how you make a clone, by the way. But, that doesn't work for for human health because as you said, if your cells lose their identity and become age zero you're not going to live very long. Um and even if you do it in a few cells, you could get cancer. So, that was the tough part. I love the way you always whisper cancer. Yes. >> Well, I I will say uh cancer's been in my family, so it's not I just had skin cancer, so I feel anyone's pain. Yeah. Well the the good news is we find that when we reprogram cancer cells, the majority of them slow down or die. So, de-aging cancer doesn't make it worse. It actually makes it die and shrink. So, that's good. I'm not so I'm not worried actually about cancer anymore. The The observer >> I'm going to up on that in a minute, but keep going. The the I'm going to call it the observer, the backup copy, cuz that's what we call it in the lab. The observer has a way of stopping the reversal at about 75%. And it works in every tissue that we've tested it in. We started with the eye and human skin cells. Um really not because the eye is easy, it's because it's really hard, but it's an enclosed system and safer to deliver it to humans than giving it IV. Interesting. >> thing. But it worked in the eye. And that was >> Because you can keep it uh localized? >> Yes. Got it. >> Exactly. Okay. >> So, putting genes into the human body is is you know, done, but it's the FDA here in the United States is much more comfortable treating the eye, cuz it's it's done every week in in patients. >> Mhm. So, we started with the eye and it was a hell of a experiment. My student, Wang Cheng Lu, who uh at one point was ready to give up cuz it was so difficult and so challenging and things weren't working. Um but he went for the eye, he chose the eye. I let him go for the eye even though I thought it was crazy to try curing blindness. But he did it and the results were clear that we could reverse the age of the eye, the back of the eye in particular, which is the problem for old mice and monkeys. Mice then monkeys. Um and then we we've moved on since then. So, the the mice were in We were doing that in 2018. Right? It was even pre-COVID we had some of these results. So, now we're you know, how many years? 7 years or so later. We've done a lot. We've done whole mouse brain. We can reverse the age of the brain. And the results are that old mice get their ability to learn and they even get, we think, get some of their memory back from their childhood. Okay. Uh-huh. Yeah. Yeah. >> in an Alzheimer's context and in old just old age mouse. Mouse >> lot of people just sat up. Yeah. Uh okay, so obviously we haven't done human trials yet, but it does this give you a level of optimism that we'll be able to um positively impact things like Alzheimer's? Yes. Now, Alzheimer's is is a big disease. Yeah. >> And it it would be a little bit outrageous for me to say it's going to be easy to cure Alzheimer's. That's crazy. But do I see a path to doing that? And why would I think that my approach is more effective than the tens of thousands of scientists that have come before me who are probably kind of pissed with me if I say this kind of stuff. The reason is that we haven't addressed Alzheimer's from an aging point of view. Most of Alzheimer's is aging. You don't get Alzheimer's typically when you're 12 cuz your brain can fight the disease even if you have the genes for Alzheimer's, APOE4 allele. You don't get it till you're 60, 70, 80. Why? Because the brain has to get old first. And what we've discovered is if you de-age the brain, the disease goes away. Yo. And that we find true for every disease we've tackled so far. How many diseases have you tackled so far? Let's Let me try to list them. Um and uh it's just just in my lab. I'm not not the only one working on this. Um we've done multiple sclerosis, all right? So, MS, we've we've published that that that is ameliorated by de-aging the nerves. Uh we've done kidney liver disease. Um a big one is ALS, motor neuron disease. Nothing you can do for those patients really. That looks like it's working um in my lab. And uh skin de-aging. We're now working on hair and hearing. Damn, man. Uh okay, so all of that is incredibly encouraging. Uh you said some positive words about your reduction in fear around cancer, but you haven't tackled cancer yet. Uh the diseases that you all just mentioned, all in mice or all in mice and monkeys? In monkeys we've only done the eye. Okay? So, in mostly it's growing human tissue from scratch. Uh well, there are two ways we do it. We either grow flat cell layers of human skin. So, if I took a biopsy uh back to my lab from your skin, I could grow a flat layer. >> skin back to that. You your uh almost middle-aged skin. I hope I'm only middle-aged. Yeah, you're you're fairly younger than me, I think. >> I don't think so. Uh yeah, I'm 49. Yeah, you're fairly younger. Yeah, I'm 56. That makes me want to punch you. I'm inspired. >> Blame my parents. >> is Well, I want to blame your protocols. I'm secretly hoping that this is all uh something I can learn to do myself. >> So, a lot of the testing that we're doing in labs is basically on just cells. >> Correct. So, we build the cells up, so it's So, we have, in theory, tested on human cells. We just grew them ourselves. >> Yes. Okay. >> That's our standard. And human cancers we grow in the lab. Lung, colon cancer, melanoma, we grow those. But we go one step better. Somewhere towards a monkey. Even better in some cases. We could We do and we could take your cells instead of making them flat we could re-differentiate them into organs or tissues. And we do that in my lab. We grow miniature brains. Get the out of here. You have miniature brain human brains. Yeah, and we give them Alzheimer's, we make them old. What? And then we de-age those with our chemicals and genes. >> Wait. Do they look like brains? >> Yeah, of course. Yeah. >> What? >> They look like If you cut them through, they've got all the structures of a human brain. >> I look at it, am I Do I feel like I'm looking at a G.I. Joe brain that actually has like all the structure of a human brain? There's no way. They're like little blobs, right? >> They're blobs, but with the same structures. Do they look like a brain? They look like >> know if they look like the thing that is on the Sistine Chapel. It's got the shape and all that. Like, is that what we're talking about? The Sistine Chapel? >> Yeah, you know that God is sitting inside of a thing that's a brain that's been vivisected. Surely. >> I don't know of that. >> What? Okay, anyway. So, the brain has a super recognizable shape. You're saying it's in that shape. This is wild. I'm coming to your lab later today. Come >> This is crazy. >> We Let's have someone from my lab take a photo, send it over. And sometimes they grow little black dots, which are eyes that grow, too. You get two little dots. This is incredible. And you can measure the brain waves. >> Can I ask, what are the ethics on this? It's If you're Are they conscious? They I don't know, but they have brain waves. Um We don't We don't know what they're thinking, though. This is insane. Okay, now I'm totally fascinated. We have to like put a pin cuz I need I have to ask. Okay, so you guys are able to replicate micro brains. How do you make them small? Well, we grow them from single cells. We We turn them into stem cells. >> Would they just keep growing and growing and growing if you fed them? They reach a certain size where they don't keep growing because they don't have blood vessels. Do they have a pituitary gland? They don't have blood vessels. How do they stay alive? We shake them in liquid and the oxygen diffuses through, but if they get too big, that the core becomes hypoxic and doesn't grow well. But what we need to do is to mix them with blood vessel cells, which people are working on. And then we could grow them really big. This is so interesting. Oh my god. >> And then it's a ethical questions about if you can grow a brain from scratch, should you teach it something? Should you give it something to think about? Yes. Anyway, it's a good model for aging. So, wait. There are, it's my understanding, AI that right now can do like these really rough like, "This person is thinking about this." And it like shows you like a horse and you're like, "It's kind of a horse." It's just like sort of blobby shapes. We need to apply immediately this AI to these brains. I need to know if these things are like screaming out, "I'm bored, bro. Like, come on. Give me something to do." This is wild. Okay. And And here's the other thing is Yep. We see them get old. They lose their firing. And we can look at them in real time. They're actually You see these sparks. It's like looking at fireworks. When they get older, there's fewer fewer sparks. >> How are you monitoring the brains? Uh Well, you put them under the microscope and we can see calcium changes. When calcium gets These are the fireworks? The nerve cells, when they get calcium Uh-huh. they they >> microscope, are they now dying at this point? No, they're living. We can put put them back. Wow. Okay. So, we see the calcium changes and wherever calcium comes in, which is what's happening in our brains right now Yeah. with the firing, it lights up with a dye, not naturally. We have to give them a dye that lights up. But you can see that. And so, you see with the old brains that are a year old that's old for a for a brain organoid. Uh-huh. If we give them our genes or our chemical cocktail, our three chemical cocktail the firing comes on again. Mhm. And we did that to a mouse, as I mentioned, and the mouse is growing old. >> is like the human brain now. Well, we we hope How close to that >> be testing this in humans. Uh-huh. For the brain as well. >> Adult humans, you're saying? >> Adult humans, yeah. Uh I don't know that I want to leave the baby brains yet, but okay, so adult humans, uh what condition would they have to have to subject themselves to this cuz this sounds experimental. Uh well, the three chemicals are where we're getting permission to give them to people in a clinical trial to see what would happen. >> But people just like, "Hey, I'm Bob. I'm doing fine, but hit me with the three chemicals. Let me see what happens." Yeah. Wow. Yeah. People do that. All the time. This is amazing. >> a phase one clinical trial. Wow. Yes. Okay. Hey, cool. That's amazing. All all so people are going to volunteer to have these are how you getting the chemicals into their brain? Oh, you just swallow it? You can take it in a pill. That's the goal. That's wild. How does this survive metabolism? Well, it's at least two of these molecules have been taken by humans already, so we know maybe all three actually by now. Wow. >> that they're metabolized. Uh-huh. But we we need AI to make improve that three chemical cocktail. Right. >> So that I don't think that's the ultimate drug that I'm going to put on the market. Uh-huh. I think though if I mention those three molecules, you could bet that people be out buying that stuff already. Yeah, didn't you say them at the top? No, I said the genes. Those are OSK genes. >> Smart. I have to be. I mean, hopefully people won't go and inject them with some salt >> Oh, they will. Apparently, they'll even just sign up for a clinical trial cuz why not? Okay. >> know some people have injected themselves with OSK already, which is Uh okay, so people are injecting themselves with this stuff. Fascinating because because they think this de-aging thing will work? Yes. Okay, even though you're saying it's there's more to it than just that. Well, just to be clear, these are these are not FDA sanctioned clinical trials. >> Yeah. They there's there's a fringe I think people should be able to do their body what they want. Do you think? So then it it's a few people in the world that are willing to try anything not to age. But getting back to really mainstream science and drug development >> I was having so much fun with the baby brains. We can go anywhere you want, Thomas. Your show. >> Yes. The uh I do want to say though that we we I'll just tick off um the diseases that have worked well. Yes. Please. >> No, I already did that. You're you're talking about in the baby brain though? Or cuz those were I thought those were like thin sheets. Yeah, I know what I wanted to tell you. That we don't just grow brains. Mhm. We grow other things. Such as? Well, we're growing a uterus. Why not? Are we impregnating said uterus? No. >> Why a uterus? Why are we building a uterus? Because to see if you can reverse fertility problems? Yes. Let's go. Well, we just in in all public disclosure, I have one X chromosome and one Y chromosome. So I'm a male. >> Fair. Yes. >> So we males are fairly dumb when it comes to female health. Yes. >> And my partner is a gynecologist and much more expert in female fertility. That said I'm a scientist and so I want to be able to help women have children for longer and even have children after they've gone through menopause. Let's go. And uh so we've we've already shown a number of years back that using a sirtuin, remember the sirtuins? I do. sirtuin activating molecule that we could reverse infertility in old very old mice, female mice, and they could produce fresh eggs and have children. That we published. That's real. But uh we I want something more potent than that um that will truly reverse the age of all parts of the female reproductive system um including the uterus. And I have a student uh Maria is working on that. That's her project. Damn. So This is wild. Okay, so give me give me just a quick timeline for this stuff has to work its way through the FDA. Like when are we talking about a 65-year-old woman de-aging her uterus and having babies? Well, you you don't actually fully have to de-age a uterus. You can have a surrogate. So I I I could hear people screaming at us that we don't need to fix your uterus. What we need is healthy eggs and a healthy sperm. Uh-huh. Uh and that's >> Wait, I'm not follow I'm not tracking the caveat. So you just said you want to help de-age the uterus. >> Well, I do because that's >> Now we're trying to soften it for the screaming people, the chattering masses in the comment section. Uh but talk to me about when So got it, there are other things that people can do right now today. Yay. But I'm saying when are we going to de-age a woman who's 65, she's been through menopause for a decade. When are we going to get her producing eggs again and a womb that can like house a healthy baby to term? Ballpark me. The uterus is early stages. We're still growing those in the lab and looking at menstrual fluid and that kind of stuff. >> Wild. Is this a full-size uterus? This isn't This isn't flat cells. This is like I would actually recognize the uterus. Yeah, we grow it from scratch and it's three-dimensional and it's in the dish. Yes. And then we're going to age them and hopefully de-age them, obviously. Well, so what but what I I can predict with more certainty because I can see where we're going with more clarity that this discovery that we made in the mice is now being tested by others in humans already. So sirtuin activator the sirtuin activator. Okay. Um it was I think about eight years ago we published that raising the levels of a sirtuin activator called NAD Mhm. that chemical which we make less of as we get older by raising that the eggs became produced and fresh again. Just from NAD? >> In a month. From raising NAD. And just last week I saw a study testing women who were not very fertile uh receiving for 10 weeks an IV each week of NAD. And if there's no positive to egg count. of egg count, egg quality, embryo quality. >> Mhm. Very rigorous, actually. And although it's the first of hopefully many studies, it was extremely promising. There was a dramatic difference two, three-fold difference between those that got the NAD IV and those that didn't. I have a feeling you want me to let go on the timeline, but I'm not going to. So ballpark me knowing certainly I know that whatever you say isn't going to be accurate, it'll just be directional. But if you had to swag me >> If that was If that study is true again, be cautious. It's one study. >> Yeah, yeah. But let's say it's true. Then I think it's likely that NA NAD IVs are going to help women who want to get pregnant. >> Yeah, yeah, but timeline. We're rejuvenating uteri here. Well, the uterus is different. Uterus is more challenging, but the egg story 10 years? 20 30 years? Okay, so NAD for somebody that's sort of on the cusp Yeah, look at that. But I want to know when we're When's the uterus? Yeah, I'm talking I'm giving you the very specific set >> Thomas, it sounds like it sounds like you really need a fresh uterus. No, but this is so interesting. >> Yeah. That the So never did I think that already on the sort of pipeline of things to be tried would we be growing brains, actual mini brains in a lab, actual uterus in a lab. Like this is thrilling, exciting, shocking, but I just this was not on my bingo card. So uh now I want to know cuz it's clearly closer than I thought. >> Yeah. Um given that we have to get through all the FDA and all that. Like are we talking 30 years? Are we talking 15 years? Like what are we talking about? All right. Well, there's there's actually there's two options. One is the FDA route, which is novel molecule, AI gives it to us. We take that. I've got a company Life Biosciences that's ready to go. Um and they're all set to go. So that usually takes five years to get through the FDA with a small molecule that's been shown to work in animals. >> But do we have 20 years of discovery still on the de-aging of the uterus or are we already pretty deep in that process? Well, we're going parallel. We're going AI to find the molecule and I said we've already done a lot of that. And then we're we're building the uteri in the dish right now and we'll just put those two together when they're ready. >> This is so wild. >> And then if that works and the mice work, then we can apply to test this in humans uh with you know adequate safety studies in animals. The safety studies take a couple of years. That's wild. All right, I want to go back to the brain. The brain is my thing. If ever there was something I wanted a a fresh new one, it would be to keep my brain healthy forever. So there are things that people do now. So you've got stuff like ketones. I will take ketone supplements. I will take uh caffeine, obviously, nicotine. So I do things to sharpen my brain now. How does that stuff compare to what you're talking about? Well, right now I think stuff like ketones are are excellent for the brain. Um yeah, I I'd be >> Similar mechanism or totally unrelated? We don't know. It's possible they're they're related because um beta-hydroxybutyrate can actually not just affect energy in the brain and that's why I drink uh actually there's a group that I'm collaborating with uh scientifically as well that are doing good studies at Ketone-IQ. The science looks really good. The brain is what I use it for. I I chug it before I do recording of the podcast that uh I'm relaunching, season two coming up. But yeah, I I find that when I'm I'm stressed and I'm having to basically take 15 pages and and remember it in a few minutes then I need that extra fuel. And we know that ketones are very good for the brain. But you're asking me, is it related to my work? What's interesting is that these ketones um and one is one that's related is pseudo related molecules. Um [snorts] they're kind of related to vinegar. These molecules actually go in and they change the structure of how the DNA is packaged to help with the methyls. It's so acute though. It's not like I can take one shot of ketones and my brain is better for a month. It's very at least for me very short acting. Yeah. So that's that's Yeah, there's so there's probably two things happening. The first is the ketones are good fuel for your brain. So what we know is when we fasted for let's say about over 15 hours, ketone levels will go up because you run out of glycogen from the liver. Uh and then the clarity, mental clarity, you might be a little angry cuz you're hungry, but the clarity is there. We all we we've probably all done this if if we if we study and we're not eating a lot, we can focus. I know I need that cuz I get distracted by every little bug around me. But the the so the focus is there and the ketones really help with the focus and I can mimic fasting and I can even enhance my fasting. I try to do intermittent fasting um as best I can. And some of these ketones, if you take it with fasting, can actually improve your ketosis. Hm. Those sound like separate mechanisms to me. One feels very acute and is a hey, there's this molecule that you put into your brain. I'm fumbling for the mechanism here and it's essentially like giving it food to run its processes faster. The other is reaching into this black box and finding these magical um the observer and getting that to work. It's magic. >> Yeah. Let's let's just take a take a pause on you [snorts] are what you eat and it's not just energy, it actually does modify the DNA and the structures that package the DNA. So let's just get back >> The ketone or the Well, the the ketones like beta-hydroxybutyrate, these molecules actually get attached. So let let me briefly explain to you how is DNA packaged in the cell cuz that determines whether a gene is on or off. We talked about these methyls. When it's methyl, it's blocked. But it's not just a string with chemicals on it, it's actually wrapped up tightly in proteins that are like balls, tennis balls. And the tennis balls come together. So now you got this big structure. If you look at them, it's called a chromosome. So these balls, they aren't just tennis balls, they actually have flags on them. Imagine a tennis ball with little flags that say read me or ignore me. Some of these flags are methyls as well on the DNA and on the balls, the protein balls, called histones. But there are other things. There's a whole semaphore of flags that tells the cell what to do at that point in the genome. And two of those chemicals, one is butyrate that gets attached to the ball, the other is acetate attached to the ball on amino acids, lysines usually. And these histones have tails. So it's a tennis ball with a a tail, a protein amino acid tail. And it's that tail that accepts these little flags. So when we know this for a fact that if you drink acetate or butyrate or molecules like we're talking about these ketones, you can change the pattern on these little flags in ways that are healthy. So that's another reason why fasting may give you a buzz or focus for a while, but long-term, if you do it for months, you will actually change your gene expression and slow down I I believe slow down the rate of aging as well. Okay. Preserve the information. >> we have reasonably that's true through fasting. Can you supplement your way there? We don't know. But there's no reason to believe that that wouldn't work because what we're drinking in these bottles, um like the 1,3-butanediol, is that is naturally there in our body anyway. We're just giving the the body more of it. These are breakdown products of fat, right? So after 15 hours of fasting, we get these fatty acids out of our fat. That's how the body uses fat. Turns them into these ketones that give fuel, but also change the regulation of genes. Some temporarily, some long-term. Okay. So that's the exogenous stuff that may or may not have long-term sort of stacking effects. But what you guys are doing now on the brain, the brain is insanely complicated. I've always assumed that part of the problem with Alzheimer's, not that the amyloid plaque is the cause, but that you would have built up so much plaque, I don't see how you start unwinding that if you're not clearing the plaque out. Do you think the plaque is um the brain knows how to get around it or does it get cleared in some way? Like how how would this look? That's a a really great question and one that we are addressing. The reason I don't know the answer yet and I can tell you what I think is going on based on other experiments in different tissues, which do clear out proteins like beta-amyloid. But we don't know in the eye, sorry, in the brain for sure. And the reason we don't know is we don't get a lot of plaque in the mouse model. Hm. We get all these other problems. There's a protein called tau, phospho-tau, we do see that. And we turn that on in the brain. But we don't know for sure yet if the plaque goes away or if the brain just can handle it better. Hm. What about all of our little mini brains? We haven't run this yet. >> No. The mini brains are not getting plaque. They just get dysfunctional with the APOE4 gene. >> Because your um like racing forward their aging so much? Well, it's partly that, but also the APOE4 is producing this APOE protein, which can cause problems inside the cell. You don't need to have these collections, these crystal crystals outside the cell to be defective. >> But doesn't that tell you that there's something different going on? So if Alzheimer's were just pure aging and part of the the phenotypical expression, which fancy word for what does it look and act like, um if the expression of aging is the some damage occurs that causes the build up of amyloid plaque, if you are to artificially, I'll put that in air quotes, but if you artificially age it and it does not build up amyloid plaques, then we know there's some different mechanism happening. For sure. Not everybody gets Alzheimer's, but we all get old. Yes. >> Alzheimer's accelerating the aging of the cell Mhm. um and causing it to be dysfunctional. But what we know is that we don't need to be clearing any plaque for the animals to get better memory and it may not be necessary in humans as well. But you bring up something just to really beat this to death, maybe this is what you were just about to say, but um how do you interpret the I get two different results. When I age up my mini brain, it does not build up plaque. Right. Human life seems to build up plaque. You might be right that the mini brains don't age 80 years, which is what humans do. Maybe we're only aging them to 40. Hm. I don't know, we don't get there. It's not a perfect mimic. >> of travel, but Yeah, I mean every model in the lab has its caveats. You got to take what you can get and right now the state of the art is mini brains getting old, but not getting plaque. But we do put those genes in there and they do get dysfunctional quicker. Hm. Um I I think it's it it's an interesting to point out that the the age reversal may clear out the plaque and the reason that I I'm optimistic that it would in humans is because we've done this in other tissues. The eye for instance builds up proteins lipofuscin uh causes macular degeneration. And to my surprise, when we reversed the age of the retina in a mouse that had those protein inclusions, they went away. And the retina regrew and became flat and nice and functional again. So there what we're finding is it's not just reversing aging, it's actually rebuilding the body to be young again. And the the best test of that was we actually pinched optic nerves and destroyed them. That's one way to test this. And what we found was the optic nerve regrew back to the brain. So even something as bad as crushing nerves causes them to regrow like they were embryos again. Whoa. Hold on. For uh my whole life I believed that nerves don't regrow. They don't. So this really is like if this ends up being predictably um repeatable, this would be huge. Well, that's why in part it got the cover of nature, which was oh my god, we're able to regrow nerves again. And it's huge not just for the eye, of course. Anyone who's broken or or could break >> like spinal injuries? Yeah, yeah. >> That's right. That's that's low-hanging fruit as well. Huh. Are there people right now? Because let me tell you, if I was a quadriplegic, I'd be like, yes, I'm first in your trial, inject the life out of me, give me whatever you need to give me. Um do we have people lining up for that one? And is there a reason that we're not already doing that? It's regulation that's stopping us from doing it because we need to make sure it's safe. Are you by any chance connected? You must be, you know so many of the same people. Are you connected to Elon Musk? No. I'll be I I don't know him at all, but I know Peter Diamandis knows him well. I know you know Peter well. Just because obviously what they're doing, we're trying to sort of bypass all that stuff. Maybe they wouldn't care, maybe it's even contrary to their business model, but um being able to fix somebody who broke their back would be obviously massive. >> Yeah. I mean it's not technology that's holding us. It's safety and rigor and regulations. I think we're we're there. It probably would work cuz the eye is no different than How profoundly is the nerve regrowing? Well, you're right, nerves don't regrow and there have been some small advances over the years. Other labs have regrown nerves maybe 5%. We got 100%. What the man? This is one of those uh >> [snorts and sighs] >> there's a there's always such a big gap between what works in the lab and what works in real life. So I'm aware of that, but this is this is very interesting. If you're able to So my wife's grandmother um I think she actually died from cancer, but she had Alzheimer's for the last goodness how many years of her life. Absolutely tragic. My great fear is losing my brain. Yeah. Um the thought of being paralyzed has always been so hopeless my entire life. The thought that you can regrow nerves is absolutely wild. >> Yeah. And for a disease like ALS where the nerves that are holding onto your muscle are retreating, degrading, regressing. We're finding that we can regrow those. One of the reasons people have falls and can't control themselves physically when they're older and maintain balance is that problem. The nerve muscle junction. >> Mhm. Get retraction. These nerves go away. We've got images in my lab when we treat with our chemical cocktail, those nerves then regrow for the first time ever in biology to go back to where they came from. What's going to stop this from being real? Like this When something seems to be too good to be true, it is too good. So, what's the what's the catch in all this? The there are making a drug period, whether it reverses aging or not, is is hugely challenging from bench to bedside as they say. There are uh biological issues. So, you might be wrong about the theory. Don't think that's the case. It may not be relevant to humans. It could just be in rodents or mice. Don't think that's true cuz it's working in monkeys already. Mhm. Um there could be safety issues. Right? But we've ticked all those off so far. So, what's left? Well, uh there's funding. You need hundreds of millions of dollars. So, I spend fair amount of my time traveling with Serena around the world to raise money to do these trials. And thank you to all the investors that have come in to help us with that. And uh that's The company's called Life Biosciences, which I'm chairman of the board of. That company um has a great team. You got to have a great team cuz you can mess up a clinical trial and not get great results. Mhm. And you got to do it the right way with the right controls. Um and then I don't know. I think that's that's pretty much it. And then it does it works or it doesn't. And if you're wondering what's the chance now, I've I've pegged it at at least 80% given that it's worked well in the monkeys multiple times. In that you're clamping down on the nerve, effectively killing it, and then regrowing it. What nerve are you clamping down on? Uh the entire optic nerve. Okay. So, you make them blind and then unblind them? And then they can see again. That is wild. Uh okay, so >> By the way, that's that's required by law. It's not something I want to do. What do you mean? Well, the the the government makes us drug developers do these safety studies in animals before we can touch a human. Meaning they force you to blind and unblind the monkey. Yeah. I wouldn't want to do that, but that's what we've done. And fortunately it worked. It cured them. They're all good. And uh >> wild. Yeah. Okay. And so, uh are you just clamping the nerve and the pressure is what makes them blind and just unclamping it by any chance? >> No, it's done differently than a clamp because it's harder to do with a clamp. >> Uh it was done with a bright light. So, you burn the nerve essentially? I don't know if you like that word choice. >> choice. It's not really burning, but it is bright enough. >> damaged? They're not going to see again unless we treat them. Okay. Are you doing it just by shining a light in their eye? >> laser. Interesting. Okay. Uh okay. So, we are overloading, frying, whatever word feels accurate uh the optic nerve, and then you're able to regrow it. That is crazy. Okay. So, Oh, and let me say in humans we're not treating laser-induced blindness. We're treating glaucoma, which is the leading cause of blindness in the world. Is that nerve related? Oh, yeah. Interesting. People think it's the pressure. But it's it's actually the pressure that's just disrupting the function of the nerves at the back of the eye. Which we can Don't you have to alleviate the pressure first? Or do you just have to keep doing this? Like the pressure takes time to crush the nerve again and Well, the pressure may come back, but there are good drugs already to lower pressure. But even if you lower the pressure, the nerves are still not going to work. >> Wild. Wild. Why Do you have a guess as to why nerves don't regrow? I've never understood that. Like so many other things in the body do, but it's like, "Oh, you broke your back. Sorry, done." Yeah. Well, that's unfortunately the cruelty of evolution. If it's not 100% nec- necessary necessary for a person to survive and it's rare enough. >> is necessary. If if all of us in in on the savannas of Africa were getting back damage, we would have figured out how to regrow, but it was so rare. By the time you broke your back, you were getting eaten. So, that's sort of game we were playing. >> But you got to keep the children coming. Um and uh it was mostly men who were getting broken backs anyway, probably. >> From war and whatever. We're expendable. That's so wild. Yeah. But there are some species that do regrow their nerves and grow regrow arms even. Uh salamanders. >> Yeah, yeah. I thought you were saying for humans for a second. I was like, "Wait." I wish. Not yet. But we know that it's possible in biology, and we actually have evidence that what we're tapping into to regrow the optic nerve and fix the liver and skin is the same process as lizards and salamanders use to regrow limbs. Interesting. Okay. So, what's the approach with skin? How do we Same idea. It doesn't matter the cell type. We're going to get these three So, wait. Can you then, if it's not an injection and we do turn this into a pill, is it just everything that can't be positively impacted by this will be? How will that work? In terms of um flash me forward that's 10 or 15 years from now. We've identified single molecule or the best combination of these, >> [clears throat] >> and are we Do you see this as a targeted thing where we go in and say, "Okay, this is the optic nerve treatment. This is the broken back treatment. This is the liver treatment." Or is it just like take this thing and it goes and de-ages all your cells? >> [snorts] >> Yes is the answer. What I mean by that is um I talked about two paths. The first path is FDA, which takes a decade or more. >> Mhm. Uh fortunately, you know, we're we're in the clinic this this next quarter. So, we've come a long way. That's on its way. But there's another path to getting this technology to everybody and democratizing it and making it cheaper and available. And that's the non-FDA path, which is going down the consumer product route. And just making it work like a supplement? It could be a supplement. Could be a cream. Could be a spray. It could be even an IV. Um I guess that's not too consumer, but but it's there are some IVs that are If it's a natural molecule, um you can get delivered like a supplement. So, where where we're at now is So, we've formed a company to spin out the molecules that we're finding. We have a patent already uh that's been filed and spun out. Uh Paradigm 88 with Serena, uh who's the CEO, my partner. And we are developing consumer products that we hope that will not be 10 years, but maybe a lot less pretty soon, that we have natural safe versions of the super drugs that we're developing that will be available much sooner and cheaper. And it could be something for the hair, for the skin. Could be a drink. Could be something like that. I won't reveal what it is. We're developing the product right now. Mhm. My base assumption is that if it can be delivered in that sort of over-the-counter fashion, that it's like some That it's not like the real deal. How is it possible that it could be so effective to regrow a nerve and yet be over the counter in an IV bag? Yeah. Well, we're not developing something to cure blindness. That's super potent gene therapy currently, or gene gene manipulation. What we're talking about here or gene introduction. We're not manipulating anybody's genes. What we're talking about here is something that undoubtedly will be less potent. But you don't need to cure blindness just to regrow hair or make your skin look better. Or to feel better. So, we're going to have something we believe available that will show by clinical trials. I'm not going to put something out there that isn't proven to work. Um that will rejuvenate the body over time. That will turn on the same mechanisms that we're currently working on. And I believe it's possible because we already have three molecules. Some of those are already natural that we can get it to work. And it works within 4 weeks. And what do we get in the mice? Might be People want to know what the heck do you see in the mouse? Well, we don't know about the hair yet cuz we were we were The mice weren't [snorts] bald. But we did see, and this was a year ago, we gave it to the mice down their throats for 4 weeks, and what we saw was rejuvenation. So, they they were better on tests of strength, memory, um balance. We have a We have a whole set of tests, about 20 of them, that tell us whether a mouse is young or not. And based on those parameters, the mouse was de-aged in 4 weeks. Okay. So, your job right now is basically to tell the AI, "Hey, here's what we've got in the industrial strength version. I need you to find a natural correlate that I can do over the counter that will work." And then you build the Done. Done. Done. Um we're at the stage of testing. But yes, we have those natural molecules at least. Okay. And are you already taking these bad boys? Some of them? Interesting. Interesting. Well, I got to say, up close and personal, you look good. Hey, thank you. >> You look good, man. Keep me posted on when these become available. So, skin, hair, Mhm. those are the ones that we're focusing on right now. Uh well, and whole body for the because it's working as a drink in the animal, we'll we'll see if we can make a drink. Got you. So, you'll feel better. But, skin and hair you'll be able to see. Right. You either have less gray hair or you don't. That one, the hair, is probably the most like non-placebo zone one that you're going to get. Yes, and and it's by popular demand everywhere I go. It's like, "David, what am I going to do for my hair?" cuz it Will they help people regrow hair or just go from gray to color? We we still have to prove it out. But, we've de-aged the skin, so we know that the skin gets younger. The hair is next. And the way we're testing that is one of the tissues that we grow in the lab besides brain and and the placenta, not placenta, the the uterus, uterus, is uh we're growing skin, human skin from scratch. And you age it and then de-age it. Yeah. Wild. Yeah, and it it's pretty cool. Do you have >> to see the the hair growing? Do you have video, anything like that of this stuff? Yeah, I could get permission. I mean, my employer, Harvard University, isn't that keen on sharing pictures of mice growing human hair on their backs, but maybe we could. I mean, if you want to talk about a great marketing campaign, uh brother. Like, if you're able to show, like, here we are aging it up, here we are aging it back down, like, people go crazy. Now, needless to say, people are going to come out of the woodwork and be like, "Yeah, it's all good at first, and then you're going to Benjamin Button or whatever." I guess he was the opposite direction. That there's going to be some complication that only manifests itself 10 years down the road. Uh and the immediate one is going to be, "Well, if the catastrophic fail status cancer, how do I know this isn't going to give me cancer in 10 years?" Well, that's why we we don't rush into these things, and why I think it's too early to be trying this uh systemically in our whole body. We'll start with the eye and see how that goes. >> You said you're already taking some of this stuff. Oh, the natural molecules, yeah. And they some of these molecules have been in ancient medicine for a while, so I'm not too worried. The safety is known. I'm not taking anything where So, you're saying there's sort of two grades of this stuff. There's the um hardcore stuff. Is it the hardcore stuff that's going to de-gray your hair or is it the over-the-counter ancient herbal Chinese medicine that's going to de-gray the hair? >> Out my expectation is that we'll find natural versions in the tens of thousands of molecules that have been in the human food supply. The the right combination of those, or maybe one, will be sufficient to fix hair. Cuz in skin it's working beautifully. The wrinkles go away, the thin skin gets thicker. >> What's the I mean, I guess you're saying we're reaching into the black box and we're just getting it to solve the information problem. This isn't like, "Oh, it's collagen." All right. It's a lot more powerful than that. You you hit a good point just there. The approach with disease and of cosmetics up until this point is, "Let's fix one thing that's missing or overproduced We're fixing everything. We're going in and changing the biology back to what it was when it was young, which affects tens of thousands of processes with a single treatment. It's crazy. It's crazy that it works. It's crazy that it's so far safe. I mean, it's a gift to humanity. Maybe that's the best proof that we're in a simulation that this stuff is actually happening. Cuz in a in the real world, you're like, "What's the chance that you get AI and you get age reversal? Come on." But, it's happening. So, whoever's watching and making this happen, maybe they're having fun. It's bananas. Uh did your dad age as well as you? He's aging better than me. Um but >> saying like before you came up with all this stuff. Like, cuz if dad looked like you at whatever 50-ish you are, then okay, you just have good genes. But, if this is dad looked like a normal 55-year-old, uh there's Yeah. more hope. Well, my my mother was would did better off, though she died of cancer, but lung cancer. She had good skin and and not a lot of gray. But, my father uh yeah, he he looks like when he was my age, 56, he looked like a 56-year-old. >> Right. Uh though it's slowed down. Anyone who's seen the photos out there, he's slowed down over the last 20 years. His aging because of working with protocols that you've been advising him on or >> Well, I'm not experimenting on my dad. He's a scientist as well. >> Damn it. Uh but he he listens and he takes a few of the things that I do, about five of them, and uh he's he physically doesn't look like he's aging and at 86 he's in better health than he has been in decades. Mhm. Uh no aches or pains. He's If you see him walk, he doesn't he doesn't walk like an 86-year-old. He just climbed the Harbor Bridge in Sydney, which is a massive thing for anybody. And for him it's no big deal. Actually, Serena and I, we did like 20,000 steps around the city before we climbed the bridge. Mhm. And at 86, most men are in in the ground or Yeah. gone. Um and my father's run out of friends his age that he can hang out with and go for walks cuz they're all very frail. And he's like, "What's the what's the big deal? I got nothing wrong with me and I'm going out every night." >> Mhm. So, you know, it might be coincidence. It's a N of 1, which is basically you can't draw any conclusions. >> Sure. But, like you say, he was old at my age looking. He'd lost his hair. It was all gray in his 50s, 60s. But, physically, he hasn't changed since then, since he started working on it. Which is about 25 years of work. Mhm. Well, if it if you can regrow hair, you've got a monster hit. If you can de-gray hair, you've got a hit. Uh and man, if you can make especially women's skin look younger, ooh buddy. I'm really optimistic that we will have a new approach to cosmetics. Like, what products out there? They all say they de-age skin, but which ones like permanently de-age skin? None. And you might you might question >> you're saying it permanently de-ages it if you keep using it. Cuz my understanding was uh that you have to pulse this stuff so that as you use it, it de-ages, but then it starts aging again, then you use it again. Right, but it's not like uh collagen or or moisturizer where a week later, you don't see it. Or Botox, which is gone in months or whatever. What we see in our studies is in the case of the mouse, we cured its glaucoma, it could see again. And then it wasn't for another third of its life that it lost its sight again. But, the good news is we could turn it back on again. So, the timeline for us is you you treat and then you treat maybe 5, 10 years later, and you just keep treating. And the treatment is interesting that we've engineered it so that you don't need to get an injection every time. You just take a drug to turn on the genes and de-age the eye or de-age the body. Um and that's a proprietary system. And it's we used a a molecule, doxycycline. Um it's used to treat Lyme disease, but we're using it over a matter of a few weeks, or really 6 weeks, to turn on those three genes, OSK. And uh so, really the de-aging comes down to one shot and then antibiotic treatment for as often as you need it. And is that uh an altered variation of the antibiotic or literally, if you want to de-age, go take Lyme medication? >> Yeah, it it is the drug, and we chose it because it was well established as a gene inducer, the way it was engineered. Ideally, we want to change that and get away from an antibiotic cuz of course, you know, you want your gut bacteria. >> Yeah, I was going to say, my wife has been hammered from too many antibiotics. >> Yeah. That said, um it was the most reliable system. And if it works, we will engineer a new system, but we know we need to make sure it works. If it fails, we're going to set the field back by years. So, we've got to make sure it works. Then we can use something else to turn it on besides doxycycline. That said, you know, if if you're a paraplegic or you've lost your eyesight, you'll take some probiotics, right, to restore your gut. Yeah, yeah. Wild. Okay, um talk to me about personal protocols. When I take a molecule, I see what happens to me before I take something else. I'm very scientific about it. So, it's taken me 25, 30 years to get to the point where I'm taking a set core set of things, and I know what each one does and in combination taking a lot more simultaneously. And when you do that, it's impossible to know exactly what the interactions are, what's affecting what exactly, right? So, it's it's different, and so it's hard to figure out if you take something, what is the effect of that molecule alone, which is the way science is generally done. Now, do you trust that like if I could run a similar protocol in terms of being able to afford it, if I were to go that crazy, are you like, "Yeah, if you're taking 80 things, but you're looking at these 36 biomarkers or whatever, if those biomarkers are going in the right direction, I can't tell you which one of the 80 things is actually doing the work or what combination, but yeah, those are the biomarkers, go for it." Mhm. Well, I I want to be cautious because there could be long-term negative consequences that you can't see with a blood test. So, first of all, it's it's not for everybody. It does require doc- doctor supervision and testing. Otherwise, if you start taking that stuff, you could react very badly. Uh you can measure the rate of aging by looking at how these metals change over time. And um it's called a DNA methylation clock, if you want to look it up. I would say that there's not one clock to rule them all, uh but we also it's still an association. We The association is never conclusive in science. >> Sure. Association though, mostly from my good friend Steve Horvath, who developed these clocks originally, he found that people with slower rates of of change in those clocks or had less age in those clocks tended to live longer and have fewer diseases. That's pretty good, but we don't know if changing the rate of your clock midlife makes a difference. Probably. Right. But that's I got to you know, you're you're very rigorous in what's and what's not, so I'm being very careful about delineating what we know and what we don't. His major assertion is I'm slowing my aging down because I believe that AI on a long enough timeline is going to make it so that humans can live forever. Do Do you see a stopper in biology that will make that impossible? Obviously, nobody knows how to do it yet, but do you see anything where it's like, because of that, there's no way we're going to be able to do this? Or to you is it just I don't know? It's in between. And now, I'm not a kind of guy that that I'm not stupid. I don't want to bet against Ray Kurzweil too much. He's been right a lot and he's talking about sing- singularity. Do you remember the day? It's in the mid Uh 2045, I think. >> Yeah, it's something like that. Now, I'd be the happiest person on the planet if if our stuff works and we can live forever, that's that's not a bad day. But I But I think that being at the the forefront of this change, there is something that concerns me that may prevent us within that time frame of becoming, you know, living for a thousand years at least. Immortality I think is is so far out there. I think it's better to talk about is there going to be a small change of 5 years or is it going to be hundreds of years or a thousand? And one of the problems with aging is that there are two types of information. There's the metals, which is the epigenetic information, and I know how to reverse that 75% multiple times. Probably eventually it'll, you know, we'll lose information eventually. There's there's no way it's 100% rever- you know, pure reversal. So, there's noise in the system, even if I reverse it. Um but where we're not very good at reversing is the genetic information loss, right? Epigenetic is cool. There's a backup copy. We found that. But there if you've lost both copies of the gene for X in a cell, there's no backup. All right? And so, trying to do that for those cells is very difficult right now. We do know how to edit genes. We can fix genes. But doing that on a cell by cell basis is beyond current imagination and technology, even imagining technology to do that. Mhm. But you can't just flood the body with stem cells or whatever. Not currently, no, cuz the stem cells that people inject, they stick around, but they don't find their niche. Um you know, you can't yet cure gray hair as far as I know by injecting stem cells. And the reason is you have to get them into that very small mac- almost microscopic niche hole where they sit. >> Right. So, no, not yet. But hopefully someone will come up with either type of stem cell or a type of gene therapy that can go into a cell, figure out what's missing or broken, and correct the genome, and then, you know, my stuff will come along and reverse the epigenome. And then I can imagine living thousands of years because I can imagine it. People say, "How thousand years? That's crazy." The reason that I think it's doable is there are already living things that last that long. Why? Because they have very stable information. There's a plant in the Namib desert that lasts for It's been around since the pyramids, some of these plants. Whoa. And when you look at their genome, they have a very special genome that protects the information and preserves it for thousands of years. We lose our information pretty fast. We kind of lost a lot of our information by age 80. Whereas these plants and somewhere in between a whale preserves information even better than we do. Mhm. It's incredible. Okay, give me one um prognostication. Where do you think this goes in the call it near term? So, what are we looking at? What changes will we actively experience in the next 3 years? And then um I'll really give you some wiggle room and tell me what it looks like 20 years from now. The next few months are critical. Um I'm going to find out if this gene therapy I shouldn't call it gene therapy. It's more of a a gene introduction. The age reversal technology, if it works in people, um the world will probably find out a year from now. I'm going to be sworn to secrecy. I'm not even going to be able to wink. It's that important. But I'm going to know in a few months if this works. Wow. But anyway, let's say a year from now, everyone knows that that it works. This is best-case scenario. And again, it's I think 80-90% chance. Then the world goes nuts. That's a chat GPT moment for biology, for aging. Cuz we've got it to work in humans. Now, the question is, now what do you do with that technology? There's going to be a a gold rush. Already there are billions of dollars um spread across my company and others, competitors. Sam Altman's company, uh Brian Armstrong, uh even uh Jeff Bezos is in this. Mhm. There's going to be a massive gold rush to try and catch up, to break my patents, to get around them, and to treat other things besides vision. And just like AI is now, uh what is it? It's only 3 years since chat GPT came? >> Yeah. It's crazy. Crazy. So, there's going to be that kind of a momentum, if this works, where the world will just be listening to every result, every pundit on this topic. That's my prediction for the short term. In 20 years, I think that whether I'm successful or not, we're still going to have somebody achieve what I'm talking about. Mhm. Um and it could be age reversal for many organs. And again, there's billions of dollars put to this, so it's Does everyone just look 25? Like Oh, I see. What What does that actually look like? It's possible that my father, who looks 86, could look like us after treating himself for a few months. >> That's wild. So, you think though it's shave maybe 30 or 40% off your life. It's not you go back to looking 25. Because like fat storage, the type of fat, where it's stored, all that stuff matters. It's not just skin. >> Exactly. So, I'm I'm hedging my bets here saying that he's going to look middle-aged. >> Right. So, it's going to be far more complicated. It's not like um you take an IV drip and like uh Death Becomes Her, like her boobs get perky again and her ass tucks up and her skin changes. It's not Yeah, it's not going to quite be that We don't know. We really don't know. I've seen nothing to suggest that that would happen. It's just We're at the beginning. We're at the beginning. It'd be like asking again the Wright brothers, you do you imagine that there'll be a Concorde jet that can fly around the world? They're like, "Yeah, of course." But we're still building the Wright flyer right now. >> Yeah. So, it's coming, no question. We We We've We've shown the biology is there and we can do it. But it's going to take some work to get to that kind of a molecule, I think. Mhm. We can take a pill and truly regenerate our entire body back to being 20. You know, that said, you do want to stick around cuz this technology is coming. And if you start early, now, eventually, imagine the the drug uh I don't know if it'll ever be over the counter, but imagine that it is. You can go down to your local store and get this stuff. It might be $5 a pill. I don't know. Something like that. And start when you're 25. And you just stay 25 for a while. Mhm. For a long while. All right? De-aging my father from 86 is much more challenging than starting at 25. Mhm. Yeah. Hurry, please. Okay, so given that we've got to buy ourselves a little bit of time while the technology gets finalized, proven, all of that. Um how should people be approaching their health with things that they can do right now today? But I I want to start by saying um I do some experimental stuff and some regular stuff. Um so, what what I'll tell you as much as I can tell everybody. Um one of the reasons that I'm starting restarting my podcast is because every day, literally, on the street people say, "When's your podcast starting?" >> Yeah, brother. It It is about time. Yeah, thanks. I've been busy working on these drugs. But now that they're in the clinic, Yeah, yeah. I've got the time now. You know, the future is set. It's going to happen or not. So, I want to start ed- re-educating everybody about what have we What's happened uh recently that everyone needs to know about. And uh so, that's coming. We're just start editing now. So, that's exciting. Very exciting. >> And it's new and improved. So, you'll see. Um Also, I just want to remind everybody that uh the stack that I had when my book came out in Lifespan, the book still true. I'm still taking what's on page 304. But I've added a few things which can we'll talk about. All right, so let's start with the fundamentals that my father takes and I take and we've been taking them for over a decade. So far so good. I'm still alive, he's still alive. Which is good. When we started taking them by the way, people said, "What are you taking that stuff for? It's It's not known." All right, so now 10 years later. First one is NMN. NMN, do not confuse with N with M&M's. All right, that will not make you smarter. >> Yeah, and I I heard your podcast about sugar the other day about sugar. >> Me neither. No. Um And we should talk about what to avoid actually. But what you should consider taking what I've started taking with my father is NMN. And I take a gram of that as capsules every day. And you just want to make sure it's really pure. Um it should either taste slightly sour like a Sour Patch Kid if you're in the US. Um or there's a form of it that tastes a bit like sweet popcorn. Do you have a Well, say more. Do you have a brand that you can recommend or is that weird given your position? >> Yeah, you know what happens Tommy is if I mention a brand it's all over the internet. Now I'm used to sell millions of dollars of product. Yeah, yeah. It's not fair to to anybody. And even if I don't mention it, my name is all over the products as well. >> So I don't want to endorse product, but I will guide people to say look for GMP pure. And you can look for it. It should be pure white. If it's not pure white, it's not pure. And it should taste like those two things. And that that's the best thing. Uh but I won't mention brands. Um I I don't want to be lumped in. Already people think I sell supplements for a living which is BS. And I don't want to make that worse. I'm I'm just a scientist developing medicines. >> Yeah, but you're you're on the internet. Welcome. Well, yeah, you and I know how AI is getting crazy. It's a wild. I can only imagine how many AI David Sinclairs are out in the world. There there's a number and and the the biggest one where there were millions of views got taken down last week, thank god. >> Thank the future. So everyone listening be beware of fake versions of me giving out health advice. So lifespan.com and the Lifespan podcast is the original. It's going to be real. Uh So there's NMN. Next one is resveratrol. That's the a staple of mine for 15 years. Resveratrol's that red wine molecule. Mhm. But I don't drink red wine anymore. Serena told me it's better not to drink and I don't. >> Yeah, and you don't drink alcohol either. So it is smart. Um I'm not as funny as I used to be, but but I do have mental clarity like never before since my 20s. >> it's rough. I love alcohol. If it was uh optimizing me, I would do it all the time. It is very enjoyable, but alas. Yeah. So what you want to do is take out the molecule without and take it without the alcohol which is what I do. I take a a small spoonful. It's It's about a gram of resveratrol. Again, look for white or slightly gray. If it's brown or brownish, throw it away. It's contaminated with other stuff. They can give you diarrhea. Fun. Yeah. So there's plenty of resveratrol out on the supplement. And again, look for 98 99% pure stuff. And I mix that with something that dissolves it because it If you put it into a cup of water, it'll sink to the bottom and it will just go straight through your tract. Most of it you will not get absorbed. You can increase that fivefold by mixing it with either olive oil or a bit of yogurt. >> Mhm. Um I I do either. Is it fat soluble? Is that why? >> Yeah, yeah. It's It's like brick dust. Yummy. >> Otherwise, yeah. So most people don't know that. And even clinical trials that have been done on resveratrol have failed because they just gave it to them with water. Interesting. Yeah, all these little details matter. Yeah. >> Okay. The third thing >> [snorts] >> is a glucose-lowering medicine. Interesting. >> Or supplement. Why not just eat low sugar? That too. The combination of >> don't do it or even if like me, my glucose is low because I am I'm a disciplined freak and if I decide I'm not eating something, that's that. Uh so my glucose lives in the mid-80s. Um you're saying even there I should take something to push it down even more? Um well, mid-80s you you could go slightly slower or lower, but um I mean, if it was uh fasting 80 No, I don't fast at 80. If I'm fasted, it's mid to low 60s. >> I see. Okay, then you're good. It might actually be you know, it might be too much for you to take one of these things. You might get hypoglycemia. Though that's not common. Um I on the other hand have diabetes in my family and without a very strict diet and one of these medicines, I'm I'm probably going to be about 100. Really? What are you eating? Um and then fasted, it's better. >> hold on cuz you're like super veggie forward, right? Yeah. So you're probably intaking a lot more carbs than I am. Yeah. I Well, I don't know exactly your diet, but I am taking a lot more vegetables than I used to. Um for health reasons, but I'm taking in the plants because I want the polyphenols in the plants as well as part of my diet. Which meat does not have. Okay, give me percentage of total calories over a year, meat versus vegetable matter. 95 plant. >> Wow, okay. Yeah, and I I changed to plants because Serena is actually vegan and I tried it and within 30 days inflammation in my body came way down >> Mhm. and glucose came down actually. So but I was I was I had a bad diet then. >> C-reactive protein? What were you measuring for the inflammation? >> C-reactive protein was the big one that came down, but I'm also measuring things like TNF alpha, IL-1 beta, IL-6. >> Yeah, see what CRP is a good way to get it down is to to cut out I cut out dairy uh and I cut out uh meat for a while. I still occasionally eat meat. I'm not total vegan anymore. Yeah, yeah. Um 5% over a year, that's not a lot. Okay, cool. Um I will say that I'm I have an advantage which is that uh Serena is in LA and I'm in LA a fair bit. It's great food in this city. Boston, not so much. Um but I also I can afford good food. So I buy the best quality foods, fresh, organic, good restaurants that cook don't overcook the food. >> Listen, my wife and I eat from a vegan restaurant routinely. I just put meat on it. I'm not kidding. But their stuff is so flavorful that I'm like give me more. Yeah. But I got to add meat. Yeah. Uh so the drugs that the drug that people typically take is metformin. Mhm. I think that's pretty well known. And you can get that online or from a doctor, but it is prescription. You need to talk to a doctor and you want to monitor your blood glucose levels accordingly and your liver. Now from other podcasts, you you go on and off metformin. You don't stay on metformin. >> I I do couple of things that's worth that are worth noting. Uh the metformin that I get in the US wreaks havoc on my stomach. I'm one of the 40% of people that have a stomach upset. The stuff that it um I don't get from the US, let's put it that way. Um when I'm acting like an Australian for example. Their their version is coated and I don't get that problem. >> Mhm. So that's actually one of the reasons that I I I changed from metformin to this other more natural or totally natural form called berberine. Okay, same idea though? Yeah, berberine >> over the counter? Yeah, yeah. I take Serena's supplement um cuz I can can trust her supplements being pure. And um but yeah, berberine has been shown clinically to reduce blood glucose very similar to what metformin does. So those are the three big ones. Um You good with those? Yeah. Yeah, so my father's on that. We recently added a couple of things to my father's regimen. Not we, he did. Uh one is nattokinase which is an enzyme that comes from fermented soybeans. Just like powder form it? Uh it's a capsule powder, yeah. Okay. I have cardiovascular disease in my family. Okay. And my father also has cardiovascular risk. Do you have a marker that you look for? Do you Are you getting ultrasounds or what are you doing? >> I'm getting uh And actually I [snorts] want to qualify. If you get really really low uh LDL-C, you can also reverse some plaque. So it's not the only thing, but it's the most natural way. And uh yes, so I get carotid ultrasounds and look at the um in IMT. You know about that? >> No. Um Not by that name. I know about that. >> Yeah, so that that measures the thickness of the wall of the >> flexibility and all that. I've had my arteries scanned before, years ago. Uh how often do you do it? Yearly. Okay. And have you seen an improvement or it just stays steady? Not yet cuz I've not been on it for a year. Got you. Okay. Report back. Yeah, yeah, I will. Good. Um so there's nattokinase. I'm also taking um half a gram of niacin, vitamin B3 these days cuz I have high levels of something that everybody should measure called LP {parentheses} little a. Okay, what is it? >> it is a lipoprotein that carries cholesterol in the bloodstream and is thought to be responsible for the the deposition of cholesterol and um inflammation in the artery. Oh, okay. And it was first found just by association. Uh people with high levels of this lipoprotein LP little a were susceptible to cardiovascular disease, but over the last 10 years, it's been steadily showing that people with high levels are really at risk in as much as having high LDL-C levels. Interesting, okay. And uh so much so that there's a lot of money being spent in the pharmaceutical industry to make a drug that will lower LP little a levels. Of course. >> And there's one that's in phase three that looks promising. Mhm. Um but I'm one of the people and my father is because of our Ashkenazi Jew heritage that we have a version of the LP little A that is highly expressed. So my levels were 34 and you'd want it to be more like 10 or less. >> Yo. So I immediately increased the levels of the statin and I know there's pluses and minuses for statins but I've been on a statin successfully since I was 29. What? My >> Wow. >> had a stroke at 30. >> Bro. >> that I'm still alive is is good news. >> Jesus. Yeah. Uh was this like a stress-induced? Was she like in World War like what are we talking about here? >> Might be that. Yeah. >> Cuz 30's young. >> She well she didn't have a very healthy childhood cuz she grew up um after the depression in Hungary. Then there was the Second World War where her part of our family was wiped out. Yeah, she Ashkenazi as well? No. We haven't been Jewish for the last four or so generations. But I recently did my uh family tree and can trace could trace back a thousand years. Oh snap. So I'm a a dis- one of probably many descendants of uh some of the most famous rabbis uh from the Middle Ages. >> Hm. Didn't know that till this this uh season. But anyway, the the the point is that gene coming from that line makes me highly susceptible to heart disease. And I've had to fight it since I was 29. A statin though, doesn't it make your [clears throat] joints hurt and stuff like that? Like I hear horror stories about statins. Not for me, no. I I of course make sure that I'm okay on a particular drug cuz we'll react differently. And for me, the statin's been great. It's not for everybody of course and there are actually alternatives now that are not statins. There's PCSK9 inhibitors which are really effective for lowering LDL and there's more to come. The drugs that are getting there for blood pressure, for cholesterol uh and alpha blood sugar are amazing. We really shouldn't be dying from those diseases anymore. That's wild. Yeah. And even cancer. The prevention for cancer is getting to the point where getting scans, getting DNA blood tests we're at a point where you have to be really unlucky to get cancer. Well, I just got cancer. So say more about that. So uh skin cancer I have lived my whole life with an abundance of caution around the sun. >> Yeah. So nobody I've been clowned on by my wife for decades because I stay out of the sun. I wear hats like ridiculous hats. I've never seen you with a tan. Bro. Yeah. So We barely need lights in here. Yeah, so what the Like any guesses? Well, people can get lung cancer without ever smoking. There there is a skin cancer you getting skin cancer without overexposure to the sun for real like It can happen. For real for real? Like what what do I how do we fight that fight? What's the protocol? Well, so the the the start is stay out of the sun which you've done. Your whole life? Bro, well first of all I grew up in Tacoma, Washington so there is no sun. And then here I've always stayed in the shade. Now because my wife is Greek and loves the sun more than anything in this universe uh there's no doubt that I'm sun adjacent a lot. So I'll be under the umbrella while my wife sun tans but I I can burn in the shade just to give you an idea of where we're at here. So uh I've had to be paranoid because I will burn so easily. Do you have any family history? >> My dad has had skin cancer multiple times. >> I did your genome have you have you done your genome? No. See cuz you could be susceptible in some ways. >> Well, apparently I am susceptible. >> Yeah and and that's another good reason for getting your genome done if you can afford it. Um it can really make sure that you do the right thing. Now besides staying out of the sun, you can also with your diet uh maybe not prevent but reduce your chances of getting certain types of cancer including skin cancer. Like? I thought you'd ask. >> Are we in the avoid mechanism here now? You said we should talk about what to avoid. >> sure but that's that's easy stuff. >> where we're headed with skin cancer or am I taking something else? >> Say more. So the polyphenols in plants one of the reasons I take a lot of plants especially colored ones. Serena says take eat the rainbow. >> Isn't there a ton of polyphenols in um olive oil? Yes. Okay. So olive oil >> Most olive oil ever. >> and green tea matcha the the thick dark green stuff with matcha >> but maybe I should. Okay. Those are highly anti-cancer. Hm. And they're preventing DNA damage. They're reducing inflammation that all can drive cancer. Interesting. >> Yeah. About to go hard on matcha then. So we do Serena again you can tell Serena played a big role in my life. The the matcha we drink every morning at least one. And I don't drink coffee much anymore instead. >> Hm. And then throughout the day I'm drinking tea and eventually caffeine free tea at after lunch. But I'm always with liquids and the matcha's been a great change to my life. And I don't own shares in any matcha companies by the way. But I do love it. And so the the kind of foods I mean there are some good books about that about how to eat to prevent cancer or treat cancer as well. Um and if you do have cancer, look into it. We talked about ketosis and uh drinking ketones. Those are They have anti-cancer properties? Yeah, there are certain types of cancers. So cancer loves sugar just like the brain. Yes. But they don't just like the brain but not like the brain they don't like ketones. So what often is recommended for someone I'll give you an example. My neighbor developed prostate cancer. Hm. Uh very common in men of course. Most of us my age we have something coming along. We uh he went immediately and he was he's an expert. I say was because he's not around anymore. Oof. But he specialized in oncology. Oh god. >> And he immediately went on a keto diet. >> Yeah. And took loads of metformin. >> this back at Quest. Yep. Uh-huh but he died. So the punchline here is not great unless he was hit by a bus and totally unrelated to the prostate cancer. He didn't die from cancer. Really? What he die from? I don't know if I should say but it it I'm too curious now. You got to say. It was depression. Really? Oh Okay. Yeah. Secondary effect of the cancer though like the treatment's grueling. >> what happened to him and of course I haven't mentioned his name so I think it's okay to talk about it. Um he was on testosterone therapy anti-testosterone therapy which for men is uh is tough and um he lost libido, he lost will to live. It was the middle of >> And coming off of it? No, while on the drug uh knocking down the levels of his hormones so that the tumor wouldn't thrive. >> Right right right. Because that he lost his manhood. >> Jesus. And went into depression because of it's common. Ugh. Um and it was the middle of the pandemic too. Oh god. So he didn't he didn't choose to stick around. Yo. That's rough. Okay. So on that note, yeah do what you can to prevent cancer. Get yourself scanned. Have you got that? I well I've obviously now I get visually scanned routinely. Um but no I have not done the like full body. I'm waiting for Peter Diamandis to open his LA branch. He's been trying to get me out to Florida or wherever the other ones are which now obviously when I got the skin cancer I was like damn it. Uh [snorts] Well well get get that scan for sure. MRI scans are good. Uh Serena and I get one of those every year. Um and that's full body. It won't pick up melanoma most likely cuz it's small. So you do need to be visually scanned. You can either get that done by your physician or by a machine. >> melanoma. Melanoma I would have been like this is a diet problem. This was another one I forget what it's called. Uh but they say this is from sun exposure. Oh so it was on a place which is exposed then. Yeah yeah, it's on my face. That's good. That's probably yeah. That's good? No no no, that's not good. I don't think I said that's good. I said that [snorts] makes sense. That it was on your If I said that's good, I didn't mean that. It's all right. I'm glad that's consistent. I'm happy for my No. facial But it's gone now and I can't see any >> It's yes, it's gone. Now. Did you Is it okay if I ask you about it? >> Yeah, I'll go crazy. >> Did you treat it with any cream? Uh no. So we looked at that option and it was going to be like three weeks of open sore on my face and then may not work. And so they were saying listen, you should just get it removed. And then I was like I don't trust you. I need to go get another opinion. And so I went and did like a deep dive on like what are the pros and cons. And given that it itself can leave a scar because it's basically like chemotherapy topically. Hydroxylurea. So I was like uh so I said let's just go to the one that's like 98% cure rate. So sorry. So I did that and Yeah. >> So far so good. So Okay, good. Yeah, this cream is is tough. Um Yeah, it's it's probably 5-fluorouracil which gets stuck in the replicating strand of DNA and kill cells that are dividing. That's wild. Yeah. Actually my father recently for the same [snorts] reason uh skin cancer on his head his bald head put the cream on. Um so yeah if you if you are losing your hair >> go okay? >> Be careful. Wear a hat. Yeah. >> went okay but you peel and [snorts] it's you know it's not good. Did it get rid of it? Um he had a surgery as well. >> Yeah, see that's why I was like I don't want to do the one-two punch. It's like if I'm going to have the surgery they should just do the surgery. Yeah. But he he also put the cream on everywhere because Just in case to like get some early stage stuff. >> often done. God it. Uh and a friend of mine did it all over his face. It was like a burning your face but he had a few and just to try and get rid of what's what's left, they do that in case there's little ones that you can't see. But I I'd recommend you do a blood test as well. I've done the blood test. >> Yeah. And the great irony was like, I knew I it had already been diagnosed, like I'd had the biopsy, and so when I got the blood test back it was like, "You're fine." I was like, "Well, then I know this thing isn't 100% cuz I actively have it right now." Yeah. Well, that's that's also something that everyone should know is that these are adjuncts that these tests these blood tests if they say you're cancer-free, doesn't mean you're cancer-free. It means you don't have anything that we know how to detect. >> Yes. Yeah. And there's also false positives as well. So, I you I use the test as a warning sign, not as a diagnosis. Very smart. But still, if you can afford it and you really want to put money into your health rather than I don't know what toys, then it's a good way to invest. Get get the full body MRI and get a blood test for cancer. And you may miss something, but you may pick something up as well. But there there are also probably doctors who are listening to this saying, "Great, everyone's going to go out and get an MRI and find that they've got some disease that isn't real." There is some truth to that that you on an MRI you can find things that are not going to kill you. And you might want to investigate. My personal view about that as a scientist, not as a doctor, I'm a PhD, is that more data is better in biology in in health. And that's why I science the out of myself and I'm also a guinea pig that I I want to learn and educate. But I don't want to shy away from learning something even if I find a false positive. You know, I'll I'd rather not live in ignorance. Yeah. No, I'm with you on that. And then you get a baseline. So, my baseline over the last few years has been perfect health. But if something changes, AI will the doctor will detect it. So, it's better to get a baseline before you're sick. In my view. All right, you just gave us a bunch of stuff uh that we should do. What about the things we should not do? Uh well, the easy ones are if you smoke, please quit. Uh my mother did not and she is no longer with me and she would be if she didn't smoke. Do not deny I'm I know you don't smoke. I never have, but don't live in denial that you'll be one of the lucky ones. It's the best thing you can do for your health is to not smoke. You'll age prematurely, too, and you'll look like at my age. Uh drinking. Occasional drink, okay, but don't drink consistently. I was drinking red wine every day. That was too much. We know that people who drink even just one glass of alcohol a day tend to have smaller brain size. >> Oh, that. Yeah. There's scatter in the plot. Not everybody's has this, but the trend line is down with the more alcohol you drink. And the more you drink, the smaller your brain will be. No, thanks. Yeah, so skip alcohol, smoking. Um sedentary behavior. We're all prone to it. We're doing it right now. Get a standing desk at a minimum. Walk, take the stairs. >> desk. And if you if you if you can run, lose your breath three times a week at least. Um I don't care what kind of exercise you're doing. Right? >> I can think of some fun ways. >> There are fun ways and you only need 10 minutes. >> [snorts] >> You don't need to be a marathon man. >> Perfect. Yeah. You're like, "Is two Is two Is two minutes enough?" >> [laughter] >> But 10 minutes will be fine for us. And uh you know, even if it's a rowing sport, it's all great, but lose your breath three times a week if you can. Uh I joke that uh I my exercise is running to the terminal to catch a plane. It's kind of like that and that does make it difficult, but um got to move. Got to move. Don't sit. And at at work, if you come, I hope you come see me in the lab, I'll be at a standing desk most days. And people on Zoom think that I'm floating in space cuz I'm doing this, but I don't I'm not still throughout the day. I even hold meetings while I'm standing. I just pace around and they think I'm crazy, but sitting is is the new smoking as they say. So, those are the the big uh do nots. You left out one that I think is mahoosive, which is sugar. Thank you. Um I've For me, it's just a way of life, so that's why I didn't think of it. Um I avoid sugar like the plague like you do. I think of it as a toxin. It's not really a toxin, but long-term it is. It will attach physically. Glucose will attach to your proteins. HbA1c, that's a prediction for diabetes, right? If you go if you probably know this, not everyone knows, HbA1c is what your doctor tests for diabetes. That's literally glucose attached to your hemoglobin as a bellwether, as a canary in the coal mine for glucose attaching to all the proteins in your body. You don't want that. Glucose attached to proteins will make them dysfunctional and who knows what else is going wrong, but we know that that causes diabetes. Glucose also will give you a spike. It'll give you you know, a real high initially, but anyone who's worn a glucose monitor will know the consequences. You will have a crash, brain fog, hunger, distraction. Whereas if you don't eat sugar, you have this steady flow of glucose coming out of your liver through gluconeogenesis, which is the term for making glucose naturally. Uh [snorts] and my liver is much smarter than my mouth. It will make pure minimal amounts of glucose that my body needs and supplement that with ketones by drink and it's it's bliss. I power through the day. I rarely get tired. If your kids are eating a lot of candy, please give them something else. No joke. >> Right? Cuz By the way, kids' epigenomes, the the methyls on their body on in their cells, those marks are laid down during the teenage years as well. And it's known that kids that eat badly will have consequences decades later because of this memory in how the genes are turned on and off. >> Yeah, interesting. And kids today are aging faster than they used to. >> That is not a surprise. >> And I think it's because of the diet. Yeah, no doubt. >> And it's no surprise that girls are getting fertile more more earlier. >> That one is distressing. Because they're getting older earlier. We are aging our children. >> Interesting. And it starts at birth. Is aging actually aging begins at the week second week of conception. >> Yeah. So, we we we're not immune even when we're in our 20s and we eat pizza and you know, a lot of us experiment with drugs and alcohol, that's aging us and you feel it at our age. Thankfully, I didn't do drugs and alcohol, but I did a lot of junk food. Yeah, I'll tell you that. Yeah. Woof. [snorts] All right, man, now that I've got you, is there anything else, any parting shots you want to leave people with, a super secret thing that they should be doing or know about, pay attention to, anything like that? Um there's there's sleep, but there's a lot of experts on that. Make sure you get good deep sleep. Deep sleep will clear out the proteins in your brain that you need to get rid of. Um including probably the Alzheimer's protein. Um A beta. Uh another thing that would be important to mention would be that stress in your life is a killer. Yeah. And it's difficult. >> my life, for sure. High achievers are the worst. And if you're a high achiever, and I I am by choice trying to be a high achiever, I spent the first 50 years of my life on edge almost every day. Even if I'd go for a walk in the forest, I was thinking about the mistakes that I'd made the day before. That kind of guy in the shower, I'm I'm swearing to myself, "You're an idiot." All that is almost all of that is gone. Again, Serena was a big influence. She taught me how to calm my mind, not worry about things so much. But it's hard. It's super hard because we are by nature many of us are driven and we want to be perfect. We'll never be perfect and we'll always have stress. So, try to think about life in the long run. Treat it like a game. It's not that serious. It may not even be real as we discussed. So, go for it. Have fun, but don't worry too much. And get get sleep cuz if you don't sleep enough you will have a high heart rate. You will feel stressed throughout the day. And I have times during the day now that I I breathe. I shut my eyes. I do box breathing. Um I've even even on occasion set an alarm at 11:00 I'm going to take time out to lower uh my nervous system down again. And it's been great. Very smart. All right, we've got the podcast rebooting. Where can people follow along and engage with you? Hey, thanks. Uh it's well, it's lifespan.com and on social media you can find me. I'm pretty prominent on most of those platforms. I would say. Uh I do work at that's fun. I like educating, so I tell people about the latest findings in science there and what I'm doing. Um and then I've got a a friends of Sinclair lab to fund my lab now that all the government funding got terminated. And uh so, if you're interested, check out friends friends of Sinclair lab. org. org. Friends of Sinclair lab.org, you'll find me there. Love it, man. This is awesome. Thank you so much for taking the time. It was wonderful to sit across from you again. And I could not be more excited about the things you're working on. Fingers crossed that they get across the finish line. It'd be incredible. Cross your fingers for us, really, cuz it's a it's a pivotal year for humanity if it works. No doubt. Thanks, so. All right, everybody, if you haven't already, be sure to subscribe. And until next time, my friends, be legendary. Take care. Peace. If you like this conversation, check out this episode to learn more. From the year 2000 to today, the average male's testosterone levels have dropped by more than 25% and modern life is only making the problem worse. Algorithms are now so effective at hijacking the male brain's dopamine system