The following is a conversation with David Sinclair. He is a professor in the department of genetics at Harvard and co-director of the Paul F. Glenn center for the biology of Aging at Harvard Medical School. He's the author of the book lifespan and co-founder of several biotech companies. He works on turning age into an engineering problem and solving it driven by a vision of a world where billions of people can live much longer and much healthier lives, quick mention of our sponsors.
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Lifespan and on the psychological maybe even philosophical level as the horizons of death drifts farther into the distance. How will our search for meaning? Change does meaning require death or does it merely require struggle reprogramming? Our biology will require us to delve deeper into understanding the human mind and the robot mind both of these efforts. Ours, exciting of a journey, is that can imagine. Now is the part of the program.
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I usually feel like the same person when I was 12. Like when I right now as I think about myself, I feel like exactly the
same person
that I was when I was 12 and yet I am getting older both body and mind and still feel like time hasn't passed it all. Do you feel this tension in yourself that you're the same person and yet you're
aging. Yeah, I have this tension that that I'm still a kid.
But that helps in my career scientists need to have a wonder about the world and you don't want to grow up a 12 year olds and even younger, I would say, six seven year olds. I've still got that boy in me and I can look at things. It's a gift. I think that I can see things for the first time if I choose to, and then explain them as I would to a 60 or six-year-old because I am that mentally. But on the other hand, I'm getting older. I don't, I run a lab of 20 people at Harvard, I've got a book. I've got science to do companies to run and so I have
to on most days just pretend to be a grown-up and and be mature but I definitely don't feel that way.
There's there's something I really appreciated in the opening of your book, you talked about your grandmother and on this kind of theme on this kind of topic. She first of all, I had a big influence on you. My grandma mother had a big influence on me and you also mentioned this poem by the author of Winnie, the Pooh, Alexander Milne.
Maybe I can read it real quick cuz I'll
on the topic of being
children. When I was one, I had just begun when I was two, I was nearly new when I was 3 hours, hardly me. When I was four, I was not much more when I was five. I was just alive but now I am six. I am, as clever as clever. So I think I'll be six now forever and ever. So this idea of
Of being six and staying six forever being youthful, being curious, being child like this and other things. What influence has your grandmother had in your thinking about life about death about love.
Yeah, I was getting misty-eyed as you read that because that that poem was read to me very often if not every day by my grandmother who partially raised me and she was as much a Bohemian as an artist philosopher and she's one of those people that wouldn't talk about the little things. She said I hate small talk, don't talk to me about politics, all the weather. Yeah, talk to me about human beings and culture, so I was raised on that and this poem was one that she read to me often because she knew
At the mind of a child is precious. It's honest, it's pure. And she grew up during the second world war and in Hungary, in Budapest witnessed, the worst of humanity. She was trying to save a whole group of Jewish friends. In her apartment, saw what happened? After the world war, which was there was the Russians were in control and locals weren't necessarily treated? Well, if they were rebellious which she was
And then there was the revolution in 56 which she was part of and had to escape the country. So she saw what can happen when humans do their worst. And her words to me I'm expressed in part through that poem was David always, stay young and innocent and have wonder about the world and then do your best to make Humanity the best, it can be and that's who I am. That's what I live for. That's what I get up in the morning to do, is to leave the world a better place and show to
Watching us whether it's aliens or some future, human historian that we can do better than we did in the 20th century.
You know, we mentioned offline, this idea of bringing people back to life through through artificial intelligence. Sort of, I don't know if you've seen videos of basically animating people back to life meaning whether it's for me person I've been working at on specific about Albert Einstein but also Alan Turing. Isaac Newton, and Richard Fineman, and it's an opportunity to bring people that meant a lot.
Others in the world and animate them and be able to have a conversation with them. At first, to try to visually visually explore. The, the full richness of character that they had, as they struggle with the ideas of the Modern Age. So if it's less about bringing back their mind and more bringing back the visual quirks, that made them who they are, and then maybe in the future,
So it's using the textual de visual, the the video, the audio data to actually compress
down the person
for who they are and be able to generate text. There's a few companies as replica, which is a chat engine that was born out of the idea of bringing the founder lost her friend too. He got ran over by a car and the initial reason she founded the company was trying to
Just have a conversation with her friend. She trained eye machine learning and natural language system on the text that they exchange with each other and try. She had a conversation with him sort of after he was gone and it's very the, the conversation was very trivial. It was obvious that it's, you know, a AI agent, but it gave her Solace. It made me her actually feel really good. And that's the way I wonder if it's possible to bring back people that are
Our, that means something to us, personally, not just
Einstein, but
people that we've lost and in that way, achieve a kind of small
artificial
immortality. I don't know if you think about this kind of stuff.
Well, I definitely think about a lot of things. That, that one's a really good one. This is great. Black Mirror episode about the wife, who brings back the the boyfriend or husband. I think, one of the challenges with bring back, Richard Fineman would be to capture his sense of humor, but that would be awesome. But yeah, bringing back loved ones would be
Especially if it's your they're young and they died early though. It may hold you back from moving on. That's another thing that could happen as a negative, but I think that's great. And I also think that it's got to be possible especially when we're recording some of us every aspect of Our Lives, whether it's our face or things, we see eventually one day, everything we see can be recorded. And then you can you can build somebody's experience and thoughts.
Speech and and you will have replicas of everybody. At least digitally and physically. You do that to one day. But that that's a good idea especially because there are people that I'd like to meet and I think it's easier than building a time machine. One person I'd like to need is Benjamin Franklin really well. I wouldn't go back in time I would but I'd prefer to bring him into the future and say can you believe we have this thinking machine in our pockets now? And he just see the look on his face as to where
And he's come because I think of him as a modern guy that just was before his time.
Yeah. So you're thinking Benjamin Franklin, a scientist, not Benjamin Franklin, the political thing, because he'd be very upset with Congress right now,
right? So maybe talk to him about science and technology and not not politics,
or maybe just don't get him on Twitter because he'll be very upset with human civilization. You know, I wonder what their personality. So like Isaac Newton, it does seem
Complicated to figure out what their personalities, like, even Friedrich Nietzsche, who I also thought about Fineman is we just have enough video where we get the full kind of, Amy shows you how important it is to get, not the official kind of book level presentation of a human. But the authentic, the full spectrum of humanity mentioned collecting data about a person, collecting the whole thing, the whole of Life, the up.
And downs, the embarrassing stuff. The beautiful stuff. Not just the things that's condensed into a book and then it was finally, you start to see that a little bit through conversations. You start to see peaks of like that genius and then through stories about him from others. And then certainly, you know, the sad thing about Alan, Turing, for example is, there's very little, if any recording of him. In fact, I haven't been able to find recording allegedly, there's supposed to be a recording of him.
Doing some kind of radio broadcast, but I haven't been able to find anything. And so that, that's, that's, that's truly sad, that it feels like, it makes you realize,
How the upside, how nice it is to collect data about a person? Did you capture that person? There's, that's the upside of the modern internet age, the digital age, that that information. Yeah, creates a kind of immortality
the. And then you can choose to
highlight the best parts of the person, maybe throw away the ugly parts, and celebrate them even after they're gone. So that's a really interesting opportunity. You are. You also mentioned to me offline?
That you're really excited about all the different wearables and all the different ways we can collect information about our bodies, about what of the whole thing is. What's most exciting to you in terms of collecting the biological data about a human being
well. So I'm a biologist, I find animals and humans as machines, very interesting, it's one of the reasons I didn't become an engineer or a surgeon. I wanted to
First and how we actually built. And so, I think a lot about machines, merging with humans and the first of that are the bio wearables. And so, I talked a lot about this, I wrote about it in life span, the book, and pictured, a future where you would be monitored constantly, so that you wouldn't suddenly have a heart attack, you'd know that was coming or you, you wouldn't go to the doctor and they don't know if it's, you need an antibiotic or not long.
How old are you? How to fix things? What should you eat? What should you take? What your jock to do these devices? I predicted would be smarter better educated than you, then your physician and would augment them. And then there'd be a human that would just take off to see if that it's correct and they approve. I also was predicting in the book that we would have video conferences with our doctors. And that medicines would be delivered initially by Courier. But eventually by drones and get it to you, sometimes in an emergency and that we could even have
Eels that we're synthesized or delivered in your kitchen and combined. Certainly, what's amazing about that is that what are we now? Two years since the book came out even less and that future is basically here, already covid-19 accelerate accelerated that is incredibly, so where we're at now in society is, if you, if you want to pay for it, you can have a blood test that will detect cancer 10 20 years earlier than it would before it forms a tumor, you can, of course, do your genome very cheap.
For less than $100. Now, there are bio wearables already. I wear this ring from aura that I have number of years of data. I've been doing blood tests for the last 12 years with a company called inside tracker, which I consult for. And so I've all of that data as well. And there's 34 different parameters on my testosterone, my blood glucose, my inflammation, and I use all that data to, of course, I wear a watch that that measure things as well, I use that data.
To keep my body in optimal shape. So I'm now 51. And according to those parameters, I'm at least as good as someone in their early 40s and I if I really work at it I can get my biochemistry down too early to mid-30s though. I like to, you know, now eat a little dessert once in a while so that's the future we're in right now. Anyone can do what I just said but in the very near future just in the next few years are you can be wearing wearable
So, I'm currently wearing a little, what's called a bio sticker. This one I just put on last night. It's about an inch long. A few millimeters for the people.
Just listen, it's Sam Davis chest. It's just a hot as it attaches. Just kind
of it sticks on six. Yeah, so on one side, you have an on button that you press the lights. Come on flashes, four times, it's good to go immediately sinks to your phone and this one, the, it's called a bayou.
A button and last name, and there's another one that I have that I haven't tried yet, that does EKG on your heart. This is mainly for doctors to monitor patients. The go home after a heart attack or surgery, but that's medical-grade FDA-approved device. So there will be a day. In fact, it's already here, that doctors are using these to get patients to go home and save a week in hospital $2,000, at least for each patient. That's massive say savings for the hospital but ultimately what I'm excited about.
a future that isn't that far off where
Everybody suddenly developed countries. Eventually these will cost a few cents and rechargeable. The only cost will be the software subscription that can be monitored constantly. And to give an idea what this is measuring me at a thousand times. A second is my vibrations, as I speak like orientation. It can tell already has told me this morning, how I slept where I slept, what side I slipped on. We've got sneezing coughing body temperature, heart rate, heart of other.
Parameters of the heart that would indicate heart health.
These data are being used to now to predict sickness. So eventually we'll have just in the next year or so the ability to predict whether something or diagnose, whether something is pneumonia or just a rhinovirus they can be treated or not, right? This is really going to not just revolutionize medicine but I think extend lives dramatically because if I have, if I'm going to have a heart attack next week and that's possible this device should
Know that and I'll be in hospital before I even have it. Maybe you can talk a little bit about inside tracker because I saw the, there's some really cool things in there,
like it actually. So maybe you can talk about, I guess that you're collecting blood to give it the data. So and it has like basic recommendations on how to improve your life. There's no, we're not just talking about diseases, right? Like anticipating having a particular disease, but it's almost like guiding your trajectory to live how to whether it's extend your
or your life or just live a more fulfilling like improve the quality of life. I suppose. This is the right way to say it. What how does inside tracker work? What the heck is exists out? There is also pretty cool. Yeah. What is it? Because it's something other people can
use you. You can definitely use it, you can sign up its
consumer. It's a good company because he will face a company
it is. Yeah, and I also want to democratize the ability to just take a mouth swab eventually, we don't need to have a blood test necessarily
Now it's a blood test and and you'd go to a LabCorp request in the u.s. it's also available overseas. You can upload your own data from minimal cost and get the algorithms, the AI in the background to take that data plot where you are against others in your age group as in terms of Health and Longevity at bio age, they call it inner age but also it provides recommendations and this isn't just a bunch of BS. It sounds like it might be to say I'll go eat this or go to that restaurant and Order.
That but it's actually based on. They've basic this company has entered hundreds. Now it would be thousands of scientific papers into their database and hundreds of thousands of human data points and they have tens of thousands of individuals that have been tracked over time and anonymously. That data is used to say what works. And what doesn't if you eat that? What works? If you take that supplement, what works. And I wasn't a co-author on a paper that showed that the recommendations for food and supplements.
Was better than the leading drug for type 2 diabetes.
That's so good idea that you can connect like, skipping the human having to do this work. You can connect the scientific papers almost like meta-analysis of the science connected to the individual data. And then based on that sort of connect your data to
whatever the proper
group is within the, whatever the scientific paper is to make the suggestion of how I called that.
At work applies to your life and then that ultimately maps to like a recommendation, what you should do with your life, like it all like this giant system that ultimately recommends you should drink more coffee or less,
right. And we'll have the genome in there as well, you can upload that. Yeah, and so these programs will know us way better than we do and our doctors as well. The idea of going to a doctor once a year for an annual General checkup, and having males, get a finger up their butt and, you know,
He cough that that to me is a joke. That's medieval science medicine and that's very soon going to be seen as medieval.
Yeah, it's a me as a computer science person. It's always upsetting to go to the doctor and just look at him and like, realize, you know, nothing about me, like you you're making your like opinions based on. Like it is very valuable years of intuition building about basic symptoms.
But you're just like, it is Medieval, they're very good at it. In
fact, doctors and medieval times will probably damn good
at working with very little. But the thing is, I'd rather prefer a doctor. That doesn't really know what they're doing but has a huge amount of data to work
with. We are right? And many of my good friends of doctors I work at Harvard so I'm not against the profession at all. Yeah. But I think that they need just as much help as anyone else does.
I wouldn't drive a car without a dashboard. We wouldn't think of it. So why would doctors do the
same? If we could, we step back to the big profound philosophical, both tragic and beautiful question about age. How and why do we age? Is it from an engineering perspective. He said, you like the biological machine. Is that a feature or a bug of the biological machine?
It is both a bug in a feature evolutionary speaking. We
Only live as long as we need to to replace ourselves efficiently. If you're a mouse, you're only going to leave two and a half years, three years. You're probably gonna die of starvation predation freezing in the winter. So they they diverted most of the resources to reproducing rapidly but they don't put a lot of energy into preserving their Soma, which is their body conversely, a baleen type of whale bowhead whale and particular will live hundreds of years because they're at the top of the food chain and they can live as long as they want. So they
Slowly and build a body at last, we're somewhere in between, because we've, we've really only just come out of the Savannahs where we could be picked off by a cat. We were pretty wimpy going back. Six, million years ago. So we we actually need to evolve quicker than Evolution will and that's why we can use our oversized brains and intuition to give us what evolution not only didn't give us but took away from us. Now we're pathetic. Look at our bodies. These Arms, if any of us even the strongest person in
the world, when in a cage with a chimpanzee, the chimp could knock that hasn't set off no question. So we're pathetic. So we need to engineer ourselves to be healthier and longer lived. So getting to aging, we can do better right whales do way better, we're trying to learn how Wells do that and if you'd asked really anybody in the field now Professor they'll say there are eight or nine Hallmarks of Aging which are really. It's a it's a word for causes of Aging so that you probably have heard.
Some of these, your listeners will have lots of telomeres. The ends of the chromosomes, like the little ends of shoelaces, that kind of thing. They get too short cells, stop dividing become senescent, they, they become they put out what it called, mitogens, that cause cancer and Implement inflammatory molecules. That's another aspect of Aging, cellular senescence. Another one is loss of the energetic. So mitochondria, the battery packs wind down, there's a whole bunch stem cells. Proteus, stasis,
as well. These are our Achilles heels that I'm talking about. There are common amongst all life-forms, really, but if you want to me to jump to, the Chase has to wear. What is the Upstream? Defining Factor? If we boil it down, what do we get? So most biologists would say, you can't buy that down. It's too complex. I would say. You can boil it down to an equation which is the preservation of information and lost you to entropy is noise and that is the basis of my research it originally.
Came out of discoveries in yeast cells, where will? I went to MIT in the 1990s. You studied bread, I kind of did I studied the the makers of bread, a little yeast called saccharomyces cerevisiae, which at the time was one of the hottest, excuse the pun organisms to work on? Yes. But they, we figured out in the lab, why e cells get old and found genes that control that process and made them live longer which was an amazing four years of my life. One of those.
Gene's had a name with an acronym sir2. NOW, the to is irrelevant. The SI R is important and the most important letter out of all of those three is I which stands for information, silent information, regulator number two, when you put more copies of that Gene in, just put in one more copy. The yeast cells live 30% longer and suppress the cause of Aging which was the dysregulation of information in the cell and then so fast forward to now. I've been looking
Humans and mice because they live shorter and cheaper to study, whether loss of information in our bodies, is a root cause of aging. And I think it is your boldness and Ewing
biology in this way is fascinating because that also leads to a kind of
It's almost like allows for Theory of Aging like, like could boil it down to a single equation and it leads to a perhaps a metric that allows you to optimize aging sort of in the fight against entropy. It's a figure out which mechanisms like I said, the, the silent information regulator which mechanisms allow you to preserve information without like without injecting noise without without creating entropy.
Without creating degradation of that information. For some reason converting biology which I thought was mostly impossible into an engineering problem. Feels like it makes it impossible to optimization to solving problems to creating technology that can whether that's genetic engineering or AI. It makes it possible to create the technology that would improve the
Degradation of information and aging is there more concrete ways? You think about the kind of information we want to preserve? And also is there. Good ideas about Regulators of that information about ways to prevent the Distortion of the degradation of that information,
right? So that we have some information regulated genes in our bodies, we have seven of them 30 137, they're called and we found in mice. One way to slow down the loss of
Nation is to just give more of these to up regulate these jeans. So we made a mouse with it has more of this 31 Gene turned it on and that slow down the Aging of the brain and preserve their information. Didn't know what information my talking about. You might ask well again, you can simplify biology. There are two types of information in the cell primarily. The one we all read about know about is the DNA the genome. And that's base for information atcg, the four chemicals that make up.
The various sequences of the genome billions of letters and that also degrades over time. But what's been fascinating? Is that we find that that information is pretty much intact in Old animals and people you can clone a dog, one of my friends in La just cloned is dog three times. So this is door. All right? That means that the genome can be intact. But what's the other type of information? It's the epigenome, The Regulators of the genetic information and physically. That's really just how the DNA is wrapped up.
Or looped out for the cell to access it and read it. So, it's similar to an excuse this analogy, but it's a good one, a compact disc, or a DVD, those pits in the foil, the digital information that's the genome. And the epigenome is the reader of that information and in a different cell, you read, different music, different songs, different Symphonies and that's what gets laid down when were in the womb and that gives makes a skin skin cell.
Forever, a skin cell and not a brain cell tomorrow. Thank God. Otherwise, our brains wouldn't work very well. But over time, what we see is that the brain cells start to look more like skin cells and the kidney cells start to look more like liver cells and they what we call X differentiate. This is a term that we use in my lab isn't yet widely used but we needed a term to explain this. And those that process of X differentiation, the loss of the reader of the CD or the DVD, we liken that to
Scratches on the DVD. So that the reader cannot fully access the information. Now we can slow down the scratches. As I mentioned, we can turn on these jeans. We can even put in molecules into the cellar or even eat them and turn on those Pathways which which my father and I have been trying to do for about a decade to slow things down, but the question that I've had is, is there a repository of information still in the body because anyone who knows anything about the loss of information or
Even has tried to copy a cassette tape or photocopy of Xerox. Anything knows that. Over time, you lose that information, you're a probably. So I've been looking for a backup copy inspired largely by Claude Shannon's work at MIT as well in the 1940s. His theory, mathematical theory of communication is just brilliant. And so I've been looking for what he called The Observer which is the backup copy. We today Michael that the tcpi protocol TCP IP protocol of the internet that stores information in case it doesn't
Make it your computer, it will fill in the gaps. And we've been spending about the last five years, to try and find If there really is a backup copy in the body, to reset the epigenome and Polished, those scratches away a bit, does incredible. So finding the backup. So whenever the too many scratches pileup, you just write a new version make a right that the neither new version but go to the backup and restore it, right? That's really all we're talking about. It's not that hard once you know the trick.
And for people that actually remember like DVDs and scratches on them, how frustrating
it is that that's a brilliant metaphor for aging. And then the, the
reader is, is the thing that skips and then it could destroy your experience. The richness of the experience that is listening to your favorite
song, right? But in biology, it's even worse because you'll lose your memory, your kidneys will fail, you'll you'll get diabetes, your heart will fail and
Call that aging and age-related diseases. So it most people forget that diseases that we get when we get old are 80 to 90% caused by aging and we've been trying to fix things with Band-Aids after they occur. Without even generally talking about the root cause of the problem
is there. The scratches, did those come from?
Are those programmed or they failures? Meaning is it? So if it's by Design, then there's like a encoded timeline schedule that the body's just on purpose degrading the whole thing. And then there's the just the wear and tear of like the scratches and a disc that happened through time. Which one is it? That's the source of Aging.
It's more akin to wear and tear. There isn't a program getting back to Evolution, there's no selection for aging. We're not designed to age. We just live as long as we need to and then we're at the whim of entropy. Basically second law of Thermodynamics stuff falls apart. We live a bit longer than age 40 only because there are robust resilient systems but eventually they fail as well current limit to human life span where they completely fail as a hundred and twenty two. But so it's a no. But I don't like to think of it as wear and tear because
Is this two aspects to it? There's a system that's built to Keep Us Alive when we're young but actually goes comes back to bite us as we get older and we call this this issue. Antagonistic pleiotropy what's good for you when you're young can cause problems when you're older. So we've been looking what what is the cause of the main causes of the noise and we've come, we found two of them definitively. The first one is broken chromosomes. When a chromosome breaks
The cell has to panic because that's either going to cause a cancer or kill the cell. There's only two outcomes is pretty much a problem and so what the cell does is it reorganizes the epigenome in a massive way. What that leads to is think of it as a tennis match or a ping pong game. The proteins of the balls and they now leave where they should be, which is regulating the genes that make the cell type, whatever it is and have to, they have a dual function. Actually go to the break the chromosomal
I can fix that and then they come back. The, you might ask. Why is it set up that way? Well, it's a beautiful system at coordinates gene expression. The control systems with the repair, you want them coordinated? Problem is as we get older this ping-pong game some of the balls get lost. They don't come back to where they originally started and that's what we think is the main noise for aging. And we've also the other cause of Aging that we found is cell stress. We damaged nerves and they age rapidly. So you
that's at the other issue. There's probably others smoking chemicals. For example, we know accelerates, biological age pretty dramatically with the question is, can you slow that down or can you reset them to get those ping-pong balls to go back to, where they originally started in the game? And we think we've found a way to do that. What? Give me, hints? Whose fault? Is it?
Involves not coming back. Is at the proteins themselves like they are, they are they starting again. I've been obsessed with the protein folding problem from
the a prospectus. Those
That the proteins, there's something else. Well we know who hits the balls and recruits them so that the brake is recognized by proteins who send out a signal through, phosphorylation is typical way cells, talk to other proteins and that recruits those repair factors those ping-pong Balls to the break. So the cells actively doing this to try and help itself but we don't know who's to blame for them. Not coming back.
That could just be a flaw in the quote unquote design. I don't think that there's something saying, well, 1% of you, you balls proteins, never go back. I just think it's hard to reset a system that's constantly changing we have in our bodies close to a trillion, DNA breaks every day and imagine that over 80 is what damage that does to our epigenomic information. Now we know that this is like well we never know anything in biology but we have strong evidence that this
True. Because we can mess with animals, we can create DNA breaks and tickle them with a few breaks. Maybe raise it by 3 fold, over background levels of normal breakage. And if we're right, those mice should get old and they do, we can actually we've created these breaks in a way. That's titratable. We can like a rheostat, we can send it to 11 and, you know, I drove my Tesla here on big fan of spinal tap to go to 11, we got 11 weekend.
Kamau sold in a matter of months we prefer to go to a level of about 4 and it gets old in 10 months but it's definitely old. It's got all of the Hallmarks of Aging. It's got diseases. It looks old. It's skin is old, it's got gray hair. But importantly, we can now measure age by looking at the scratches. We can look at the epigenome, we can measure it and use machine learning to give us a number. And those mice are 50%
older than normal, so you can replicate the aging process in a controlled way. You can order mean in a way
I mean you could accelerate it in a controlled way and measure how much exactly its aging and that gives you step one of a two-step process to when you can then figure out what how can we
reverse this? And now we're reversing those mice. Is there a good?
I love you said. I mean in biology you really don't
know.
It's such a beautiful mess. Is there is their ideas. How to do that. Is that on the genetic engineering?
Ring level. Is that like, what can you mess with? Is it going to the trying to discover the backup copies and restoring from them? Like, what's if it's possible to convert it to natural language, words? What are the ideas here? What is the Observer? And how do we contact the exactly what's the Observer? And how do you contact or if there's other ideas, how to reverse the the the
balls getting lost process? Yeah, when you can slow it down, slow it.
But we found that a reset switch recently. We just published this in the December 2020 issue of Nature. And what we found is that, there are three embryonic genes that we could put into the adult animal to reset the age of the tissues and it only takes four to eight weeks to work well and we can take a blind Mouse. That's lost. Its vision due to aging neurons aren't working well towards the brain reset. Those neurons back to a younger age. And now the my scan
See again these three genes are famous actually, because they're a set of four genes discovered by shinya yamanaka who won the Nobel Prize in 2016 for discovering that those for jeans. When turned on, at high levels in adult cells can generate stem cells and this is I think, well know now that we can create stem cells from adult tissue. But what wasn't known is, can you partially take age back without becoming a tumor or generating a stem cell in the eye, which would be a disaster.
And the answer is yes, there is a system in the body that can take the age of a cell back to a certain point, but no further safely and reset the age. And we're now using that to reset the age of the brain of those mice that we age prematurely and they're getting their ability to learn back.
This is really exciting. Right? Like what's what's the downside of this?
Well, the downside is if you overdo it and you don't get it right? You might cause tumors but we do it, we do it very carefully and we also know that in the eye, it's very safe. Yeah we also injected these, we get deliver them by viruses. So we can control where and when they get turned on and in this paper we published that if we put high levels in the mouse, into their veins throughout the body,
They don't get cancer for over a year. So I'm so optimistic that we're going into human studies in less than two years from now.
Is there a place where a I can help? Sorry to inject. One of the things I'm very excited about and passionate about. So deep. Google deepmind recently had a big breakthrough with Alpha fold to but also have a fold two years ago with achieving
I'm sort of state of the art performance on the protein folding problem, single protein folding but it also paints a hopeful picture of what's possible to do in terms of simulating the folding of proteins, but also simulating biological systems through AI. Is there something to you combined with This
brilliant work on the biology side that you're hopeful about where a I can be a tool to help where isn't that a tool and if you're not using
Aii right now in biology you're getting left behind. We use it all the time. We're using it to generate these biological clocks to be able to read those scratches. We're using it to predict the folding of proteins, so we can Target molecules and modulate their activity. We're using it to assembled genomes of different species. What else we use it to predict the longevity of a mouse based on how it reacts to certain things hearing eyesight generally Frailty. So we have, we just
Put out a paper last year on that. The other thing we can use it for which is a little off the track here about. We use it for predicting, which microorganisms are in your body, actually not predicting telling you. So our daughter Natalie was infected with Lyme disease. A few years ago, almost went blind from it and the test took four days. And I thought just give me the DNA from her spinal fluid. I'll go tell you what's in it if it's Lyme disease or not, they refused. And so at that point I said this has to be done better.
So I started a company that now can take a sample of any part of your body. It's typically done. Now, with transplant, Trent liver transplant, patients to detect, viruses that come out of their organs. But that's that's another area that AI is extremely important for. I think, if you're not in five years, if you're not using deep learning, you've got a problem because the amount of data that we generate now is biologists is just terabytes can be terabytes per week, will eventually be terabytes per day.
And then we just go from there. And I actually have trouble recruiting enough bioinformaticians. A lot of our work is now just number crunching.
Part of that is collecting. The data would just kind of something. We've talked a little bit about, but, is there something you can say about how we can, like, can collect more and more data? Not just on the one person level like for you to understand
You're like, various markers, but to create huge datasets to understand how we can detect, certain pathogens detect, certain properties, characteristics, of what there is aging or all the other ways that human body can fail. It seems like, with the biology.
There's a kind of privacy concerns
that well actually not privacy concerns almost like regulation that kind of prevents like, hospitals and sharing data.
You know, I'm not sure exactly how to say it, but it seems like when you look at a Thomas Vehicles, people are much more willing to share data. When you look at human biology system, people are much less willing to share data is there, a hopeful path forward where we can share more and more data at a large scale that ultimately ends up helping us understand the human body and then treat problems with the human body.
So, we are right in the middle, we're living through, what's going to be seen.
It is one of the biggest Revolutions in human health. Through the Gathering of data about our bodies and 20 years ago. People didn't want to go on social media that worried about it. Now you have to if your kid that's for sure. Same with medical records, these are becoming old, digitized and expanded. Ultimately we're going to even if we don't want to have to be monitored, there's going to be a cold case that I bet to three years from now. Someone's going to say how come
Father died from a heart attack. You had these biosensors 20 bucks and you didn't use it lawsuit right there and suddenly all hospitals have to give you one of there will be a reversal like to wear. It's your fault. If you don't go like the data, that's brilliant. That's and that's absolutely right. I mean, that's
absolutely right. That's the frustration. I feel I'm going to the doctor is like
your, it's almost negligent.
To not collect the data because you're making, if there's something really wrong with me and you making decisions based on very few tests, that's almost negligent. When you have the opportunity to collect a huge amount more
data. Well, like, let me tell you something likes. The I've got this inside tracker data for, for myself, over a decade and you'd think my doctor would roll his eyes at this. Always gone to a consumer company, blah, blah blah. I had my first check up in a year with him through video conference
And he was running blind. He really didn't know what was going on with me. He asked the usual things. How am I sleeping? How am I eating these kind of usual things and as well. I've got new test back from inside track her and he said, great, I'd love to see them. So I share screen and we look at the graphs, look at the data and he's loving it because he cannot order these tests willy-nilly. So I said, well, let's order a hba1c blood glucose.
Because I'm very interesting that that tracks with longevity and he said, well I have no reason to order that you have a family history. No, are you Japanese symptoms of diabetes? No, well I can't order the test. I almost wanted to reach through the computer and strangle him but instead you know, I pay a little bit to get these tests done and then he looks at them. So that's now the way consumer health is going is that you can get better data than your doctor can and but they'd like you to do
that quick human question, maybe you can educate me.
I've I think dr. Sometimes several Bevin ego, I understand that the doctor is super experienced a lot of things but this is a fundamental question of human variability. Like I know a lot of specific details about like that mean depends, of course what we're talking about but there's a I bring a lot of knowledge and if I have data with me then I have
like several orders of magnitude more knowledge
and I think there's an aspect to it where the doctor has to put their
Art hat, like take it off and actually be a curious open-minded person and study, and look at that data. Do you think it's possible to sort of change the culture of the medical system, to where the doctors are almost? As you
said, are excited to see the data or that's already happening. It's really happening. Now, we've probably lost The Lost Generation. That that no hope is. But so I teach at Harvard medical school and they're excited about this, they're excited about aging which is a new ass.
Aspect to medicine or well, we can do something about that and then you're all this data, what do we do with it? There's still the traditional pathology and all that stuff, which they need to know, but time will change their their mindset. I'm not worried about that and like we were discussing. This isn't a question of if it's just a matter of when and it's, you know, I have a front-row seat on all of this. I had breakfast with it with a CEO who is making this happen. I just yesterday.
I can tell you for sure that most people have no idea that this revolution is occurring and is happening so quickly. If you're running a hospital and you can save $2,000 per cardiac patient, what are you gonna do? You have to use it otherwise you know, the hospital down the roads going to be beating you and there are large Hospital aggregation. So there's Ascension and others that just have to go this way for budgetary reasons and
Right now, the u.s. spends what it's 17 percent of their GDP on healthcare. For let's say one of these buttons on my chest cost, 20 bucks is rechargeable, and it can predict People's Health and save on antibiotics for prevent heart attacks. How many billions if not trillions of dollars, will that save over the next decade.
Yeah. So when the public wakes up to this they'll almost demand it like this. This should be, this should be accepted everywhere. This is obviousness a, a lot of money is going to improve the quality of
life well and the cfo's of Hospital. Yeah, groups will have to and insurance companies are going to want to get it on there. So now that gets the Privacy right? If should an insurance company have access to your data? I would say no, but you could voluntarily show them some of it if they give you a discount and that's also being worked on right
now,
I hope that we do create kind of systems where I can volunteer share my data and I can also take the data back, meet me like delete the data request deletion of data and then maybe policy creates rules to where you can share data, you could delete the data. And I think if I have the option to delete all my data that that a particular company has, then I'll share my data with everyone but I feel like if
Because that gives me the tools to be a consumer and intelligent consumer of giving of awarding my data to a company, that deserves it and taking it back. When the company is behaving and that way encouraged as a consumer in the capitalist system, encourage the companies that are doing great work with that data.
Well, yeah, Healthcare data. Security is number one on, on my mind inside tracker made sure. That that was true. It
The these buttons on your chest, there's very private stuff. They can probably tell if you're having sex one night, right? So this is not the kind of stuff you want leaked. Yeah, so I don't know, whether it's blockchain or you
call yourself. I want this
public live stream as it depends on how you how you go. But yeah, you know, there's a lot of stuff you don't want out there and this definitely has to be number one because it you know, it's one thing to have your credit card information. Stolen another thing you health records are permanently out there.
Yeah.
So this is it on the biology side? Super exciting ways to slow aging, but there's also on the lifestyle side, I've recently did a 72-hour fast just an opportunity to take a pause and be, you know, appreciate life. Think about. Like, there's something about fasting that encourages you to reflect deeper than you. Otherwise might the time kind of slows and you also realize that you're human because your body needs food and you start to see you
your body's almost as a machine, then that takes food and produce thoughts. And then, and then ends breathe. I mean, there you start to depending who you are, if you like engineering mind that you start to think of, this whole thing is the kind of as a machine. And then also feelings fill this machine feelings of gratitude of love but also the uglier things of jealousy, and greed and hate.
All those kinds of things. He started to think, okay, how how do I manage this body to create a rich experience? All that comes from fasting for me anyway, but there's also health benefits to the fasting. I intermittent fasting a lot. I eat, just one meal a day. Most of the time, is there something you can say, about the benefits of fasting in your own life? And in general, the
anti-aging process? Well, you're a philosopher to
sorry, I apologize.
No, I'm impressed.
True renaissance, man. It's a joy to be here. So when it comes to fasting, this is being, abstemious is one of the oldest ways to improve health, probably. They knew this 5,000 plus years ago, so that's not new. But what we're figuring out is what is optimal and how does it work? And one of the things we helped contribute to which I can speak to with some Authority, is that these longevity genes we work on. We showed back in the early 2000s are turned on by fasting.
And at least in yeast, we were the first to show that how calorie restriction fasting Works to extend lifespan. That was the first for any species. Something similar happens in our bodies when we're hungry or put our bodies under any other perceived adversity, such as running a bodies think, while we are getting run chased by a cyber tube saber-tooth cat or something. If we're really hot or cold, these probably also work to put our bodies in this defensive state to activate these genes in the way that whales do and my stone
And So Hunger is the best way to do that. In fact, I don't think you have to feel hungry, you can get used to it. But if there was one thing I would recommend to anybody to slow down, aging would be to skip a meal or two a day now. It doesn't mean you don't have to live. Well, you can go out. I go to restaurants. I eat regular food, I try to be as healthy as possible, but I've gone from skipping breakfast, most of my life. Now just skipping lunch as well. And I have my physique fact that I had
when I was 20, I feel 20 mentally, I'm much sharper. I don't feel tired anymore sleep. Well, so I'm a huge fan of the one meal a day thing where I'm not good at is going Beyond one day, but
if I ever have lasted longer than than 24 hours, I tried doing two days,
I might have made it to the third and given up. I'm I just find that. I'm not very, I don't have a lot of willpower. I also hate exercise. So I'm not sure how long I'm going to live, but I've
To do one meal a day. So if I can do that, seriously, anybody can do that to your listeners and viewers. I would say don't try to do it all at once. You can't go from snacking and eating three meals a day to what I do. Easily work your way up to it but also compensate with drinking. If you like tea, if you like coffee, put some milk in it. That's fine. You can fill your stomach up with with liquids diet sodas, I get criticized for drinking that I'm going to continue to have those but that, you know, I power through the day.
A I definitely don't feel tired, I don't have a lag anymore, but get also, give it at least two weeks because you there's a habit as well, having something in your mouth chewing feeling that fullness, you can break that habit and within two three weeks you'll have done
it. Absolutely. So, I'm not actually, even the strict about it, he said, dad, so too, yeah, people are very kind of weirdly strict about fasting the rules and fasting. Like, for example, I drank element electrolytes when I was fasting and that has like, five calories,
And so, technically, it's not fasting or people will say, like, if you drink coffee, there's caffeine and they'll say, that's technically, not fasting, because there's some
kind of biological effects of caffeine, whatever. Of
course, there's like biological benefits that you can argue about, but there's also just experiential benefits, just calorie restriction. Broadly has a certain experience to it that like for me personally just as you said has made me feel really good. That said,
like especially
Gained
quite a bit of way like maybe even like 15 pounds. I'm like that. Since I moved to Austin Texas and I still keep the same diet but I eat a lot of meat in that one just because it's delicious. Because it's also the the all the amazing people I met in Texas, it's just there's like camaraderie a friendship of love to the people that like makes you really enjoy the
the atmosphere of
The brisket in the mean, is this Joe Rogan and insisting?
Joe is, let me is very different, Joe loves bread and pasta, like he knows that his body feels best
doing keto carnivore.
So that's what he usually tries to stick to. But he also does not hold back and he'll just eat pasta when he does pasta and he sort of enjoys life in that way. I can't, I don't know how to enjoy life and that way,
I
I also love pasta but I'm just not going to enjoy it because I know
I know my body ultimate does not feel good with pasta, so it's a funny kind of dichotomies. I would like to cheat I guess by eating more
meat that I, you know, like overeating
on the things that I know my body feels good on as opposed to eating stuff, I shouldn't like cake and all those kinds of things. I tend to
I tend to find happiness and
overeating, the good stuff
versus eating the bad stuff and the the kind of
balanced him.
He's like, fuck it
every once in a while, you got to enjoy
it. And then also coupled with that for him is just exercise, like then face his demons the next day and just like burn, a huge amount of calories, which is, I mean,
whatever. Whatever is up with that guy's
mind.
There's a there's a ability to fully experience life which is represented by the pasta and the ability to just like fight the demons which is represented by all the crazy Kettle balls and and running the hills and all this kind of stuff that he does. That takes a lot out of you doing that kind of insane exercise and I think I'm more like You released towards your direction is like I really hate exercise so I do it but I really hate it and so
The balance that you have to strike. Is there something you could say
about the diet side of that
for you personally, but in general in order to achieve calorie restriction, like, for me eating I do may not sound healthy, but eating carnivore eating mostly meat. Has been has, made me feel really good, both mentally and physically. Is there something you could say about the kinds of diets that may improve longevity? But also
Enable calorie
restriction. Well, sure. I mean the first thing that's important to know is that while many people are interested /, obsessed with what they eat, the data that's come out of animal studies. At least, is it's far more important when you eat, then what you eat. And this was a fantastic study a few years ago by my friend Raphael de Cobo. The National Institutes of Health in Bethesda and he had 10,000 mice on different diets hoping to find the perfect.
Mix of carbs, protein and fat. And it turns out that the only ones that lived longer, the ones that only ate once a day and so that if we're not mice, but I think that we're close enough to mice that this tells us a lot, but okay, but I still think the best bang for the longevity bark is to do both well, eat less often and eat the right things. Now, I'll preface this to say I'm not a nut about this. I will eat occasional very occasionally, a desert.
Steal from others, which doesn't count, right? Exactly. But you gotta live life, right? What's a long life? If it's not enjoyable anyway, but what have I also found in this is I'll get to your question in a second, but my microbiome right now and stomach is at a point where if I try to overeat on a steak, which I did a couple of days ago, actually had a chicken fried chicken specifically for two days. I felt terrible. I couldn't sleep. It wouldn't go down. So I'm now at a point where even if I want to be
John meat and fried foods. I just can't it just feels bad but what what do I recommend? Well what the data says which I try to follow is the plant-based foods will will be better than meat based foods and I know that there are a lot of people disagree but one of the facts is was a few facts. One is that people who live a long time tend to eat those type of diets, Mediterranean Okinawa diet, they're eating mostly plants with a little bit of meat and not a lot of red meat. And the other fact is that in animals, we know,
That there's a there's a mechanism that's called mtor, a little m, capital T, or that responds to certain amino acids, that are found in more abundance in meat and when it responds it actually shortens life span and the converse, if you starve, it of those three amino acids in mostly in meat, then it extends lifespan. And there's a drug called rapamycin which some people are experimenting with that. Does that? So, you might be able to, I'm just saying this here from all my colleagues. We don't know the results here but you could
Actually take a rapamycin like drug and counteract the effects of meat on in Long Run. Don't know, we should try that. Actually could do that in the lab but getting to the bottom of this, what I think is going on is that just like testosterone and growth hormone you will get temporary, maybe not temporary immediate health benefits, you'll feel great, you'll get more muscle energy but the problem is I think it's at the expense of long-term Health and Longevity.
Well, this is actually something a worry about Juris of long-term effects or the cost. In terms of longevity, is very difficult to know how your choices affect your longevity because the impact is down the line. Like just because something makes me feel good now, like eating only meat. Makes me feel good. Now I wonder what are the costs
online? Well, think about what I was saying about the trade-offs between growth and
Production which is what a mouse does and a whale that grows. Slowly reduces slowly lives a long time. It's called the Disposable. Soma Theory Coke would discuss proposed that in the 70s. What meat probably does is put you in the mouse category, super fertile, grow fast heal fast, and then if you want to be a whale, you should restrict meet and do things that promote the preservation of your body,
is it difficult to eat a plant-based?
Diet that you perform well under. So mentally and physically just almost I'm asking almost like a anecdotal question unless you know, the
science.
All the signs are still being worked out, but from the synthesis of everything that I've read, I try to eat a diet, that's definitely full of leafy greens. Particularly spinach is great because it's got the iron that we need, plenty of vitamins. I also try to avoid too much fruit and berries, particularly fruit juice, definitely avoid that Sugar. High, spiking your sugar is not healthy in the long run.
The other thing that's interesting is we discovered what are called what we call Zeno hormetic molecules. Let me unpack that because it's terrible name and I take full responsibility with my friend Conrad, how it's busy? No means cross-species. And hormesis is the term that what doesn't kill you makes you live longer and and and and be healthier. And so we're getting cross-species, Health improvements by molecules that plants make, and plants make these molecules when they're also under.
City or perceived adversity, for instance, our I understand if you want really healthy or good oranges, you can drive Nails into the bark of the tree before you harvest, same with wine, you typically want them to be dry before you harvest. Well, covered in fungus, and that's because these plants make these colorful and Xenon traumatic molecules that make themselves, stress resistant, turn on there. So to and offenses, the surgeons remember? And when we eat them, we get
Those same benefits, that's the idea and we've evolved to do. So this isn't a coincidence. It's my theory a theory that we want to know when our food supplies is under adversity because we need to get ready for a famine and so we hunker down and preserve our body. And by eating these Colored food so I practically speaking if it's full of color or if there's been some chewing by a caterpillar caterpillar Organic Grown locally in local farms, I'll eat that versus a watery insipid. Light-colored
Let us that's been grown in
California. So you are vegetables that have suffered you want the David Goggins is a vegetables that's zero automatic
molecules I love that. I'm going to take that one with honey. Thank you. Yeah. If
I follow my Instagram is always screaming. So you want the that he's basically the the thes, you know, hermetic version of a human. I like it. So these are the molecules that are representative of
stress that it's been that plant has been
under yet. The best example of that is Resveratrol which many people including myself take as a supplement, grapes, grape Vines produce that in abundance, when they're dried out, or they have too much light or fungus and that we've shown activates the sir to enzyme in our bodies, which remember is what? Extends lifespan in yeast and slows down aging in the brain. There's
beautiful. Yeah, attend to avoid fruit as well.
Green veggies, anything that's not very sweet. So I will just say you're relatively low like you try to avoid sugary things
as well. Yeah, I'm fairly militant about that. I rarely would add sugar to anything. Occasionally I would eat at A Slice of Cheesecake but that would be maybe once or twice a year. You have to give you an occasionally, but yeah, if anything that's sweet. I would rather substitute something like Stevia. If I need a sugar hit
What about exercise? Your favorite topic
is there a, is there a dog talking about it? Yeah,
okay. Great as their benefits to longevity from exercise.
Well, no doubt. That's that's proven just like fasting pretty clear that that works. For example, there are studies of cyclists, it was something like people that cycle over 80 miles a week, have a 40 percent reduction, in a variety of diseases, certainly heart disease.
So that that's not even a question. But what's interesting is that we're learning that you don't need much to have a big benefit, it's an asymptotic curve. And in fact, if you overdo it, you probably have reduced benefits. Particularly you start to wear out joints, that kind of thing, but just 10 minutes on a treadmill, a few times a week getting, you lose your breath. Get hypoxic because it's called seems to be very beneficial for long-term health and that's the kind of exercise that I like to do aerobic though. I do enjoy lifting weights, so that is
What I call my exercise which has other benefits including maintaining hormone levels male hormone levels but also really why I do it is I want to be able to counteract the effect of setting for most of the day and as you get older, you lose muscle mass. It's a percent or so a year. And I don't want to be frail when I'm older and fall over and break my hip, which is, which happens every 20 seconds in this country.
So maintaining their strength, but also doing the cardio for the longevity for the avoiding the heart disease.
Yeah, I definitely just like, with fasting have the philosophical benefit of running long and running slow I enjoy because it kind of clears the mind and allows you to think, actually listen to Brown noise as I run. It really helps remove myself from the world and just like zoom in on particular thoughts.
What are these Brown noise?
It's like white noise. But deeper. So like the white noise is like and then brown nose is more like,
like ocean. That sounds great. I might try that. Yeah, yeah. It's soothing probably I'm not sure they could be sized
to this. I need to look this up. I've been meaning to. But I've when I started
this is maybe like five years ago, I started leasing Brown noise when I work and the first time I listened to it, something happened to my mind where he just went, like, zoomed in to, like, in a way that it felt like really weird like how how precisely it was able to sort of
remove the distractions of the world,
and really helped my mind obviously,
like the mind is trying to focus and then you just enable that
Process of trying to focus
on a particular problem. I don't know if this is generalizable to other people should definitely try it. If you're listening to this, maybe it's just my own mind, but it's funny like it made me. Brown noise made me realize that there's probably hacks out there that work for me that I should be constantly looking for. It's almost like an encouraging and motivating of event that maybe there's other stuff out there, maybe there's other
Brown noise like things out there that truly like almost immediately make me feel better. I don't know if it's generalizable to others but it does seem that it's the case that there's probably for many other things like that, that could be discovered. And so it's always disappointing when I find things in life that I wish I would found earlier. I had got Lasik eye surgery a few years ago and the first thought I had. Like the next day when I woke up is like
Damn it. Why didn't I do this way earlier? There's all this stuff of that nature that are yet to be discovered. So, paste to explore.
Yeah, though you have a different mind. You have quite a beautiful mind. So I suspect Brown noise, helps you focus and cause you're probably all over the place if you don't control it. Yeah,
exactly. It means something about it. It's a programmer thing. I don't the program is a really difficult.
Mental Journey because you have to keep a lot of things in mind. You have to, you're constantly designing things and you have to be extremely precise by making those things Concrete in code. You also have to look stuff up on the internet to sort of feed like information and looking up stuff on the internet internet is full of like distracting things. You have to be really focused in the way you look stuff up and pulling that information. And so it requires a certain other
In a certain Focus that I've been very much exploring how to do like, I do really well in the morning coffees involved. All those kinds of things. You're trying to optimize keeping very positive inspired, no social media, all those kinds of things and trying to optimize for and everybody has their own kind of little journey that they tried to understand you get this from like writers. When you read about the habits of writers like the habits, they do in the morning, they usually write like to
Three, four hours a day. And that's it. It's like they optimize that ritual and then there's always on our thoughts and
so
sometimes it pays off to be wild. What about sleep? How important is sleep for longevity?
I would guess based on evidence that it's really important and because if we don't know for sure but we know from animal studies is the following if you restrict sleep from a
For Just Two Weeks, it'll develop type 2 diabetes. It's that important. So that's the main thing. What we also know is that the molecular level, that if you disrupt your sleep, wake cycle school so we actually proteins that go up and down the control our sleep/wake, all of us, most of our cells do that. If you just drop that you'll get premature aging and guess what? The opposite is true. That as you get older that cycle, the the amplitude becomes diminished
Shhhhht. And this is why it's harder to get to sleep, as you get older. And then you got all sorts of problems. And I think, what's going on, is this positive feedback loop, which is a disaster in your old age, which is right. Your aging can't at this moment, totally prevent that. And then it's disrupting your sleep and you get not enough sleep and then that's going to accelerate your aging process. And so it's known that, the people who are shift workers are more susceptible to certain age related diseases. So your bottom line, you
We want to work on that. It's one of the reasons I have this ring on my finger, which helps me optimize my sleep and learn what I do the day before, if it was a bad idea, and I'll stop doing that like eating a fried chicken.
I see, you're still carrying the burdens of that decision but is yeah, you know, sleep is one of those things that's making me wander about the variability between humans a little bit and how science is often focused on. Like it's not often.
Gaston High performers in a particular way.
And it's looking at the aggregate versus the individual cases, for example, like, for me, I don't know what the exact hours are but like, power naps are incredible. I tend to look at the metric of stress and happiness and joy, and try to optimize those. So decreasing stress increasing happiness, and using sleep as just one of the tools to do that because like hitting the five, six, seven, eight,
Eight, nine hour, mark, or whatever. The correct Mark is, I find that to be stress-inducing for me versus stress relieving, like, thinking about that. I feel best if I sleep sometimes, for eight hours, sometimes, for four hours, and then power nap, and as long as I have a stupid private usually smile on my face. That's what I'm doing. Good as opposed to getting a perfect kamado sleep, according to whatever the latest blog post is
And I also pull all-nighters still. I also think there's something about the body, like, as long as you do it regularly, it's not as stress-inducing like you know what, you know what it is. The reason I pull all-nighters isn't for like I'm playing Diablo 3 or something. Is because I'm doing something. I'm truly passionate about, well like most a lovely against, but I'm doing something. I'm truly passionate about and it's almost like there's the Jocko willing feeling of what I'm up at 7:00.
I am and I haven't slept all night and still am working on it. There's a kind of a celebration of the human spirit that I really enjoy like and that's happiness and to sort of then. And I usually don't tell that kind of stuff to people because the their first statement will be like, you should get more sleep. It's like, no I'm doing stuff. I love you should get more love in your life. Bro.
That's right.
So but that's said in aggregate, when you look at the
The full span of life is probably, you should be getting a consistent amount of sleep and it seems like it's in that seven eight, our range.
Yeah. But it's similar to food. It's the quality, not the quantity and and when you get it. So I look at my data pretty often and what makes a difference to me is not the amount of hours but the quality of the depth and the Deep Sleep is what what I'll do it. So if I have a lot of alcohol,
For going to sleep and I can see my heart rate being different. But what really kills me is that I don't get a lot of that deep sleep. And I wake up, you know, Bailey remembering stuff. So that like you say, if you're happy and contented and you're not, don't have these cortisol chemicals going through your body. You are more naturally get into that deep State and even if you just get four hours way better than eight hours of, none of that. Yeah. Yeah, that's
beautify. And some of that could be genetic for me. I just, I fall asleep like this, that uncooked if you want me to fall asleep.
I know I can do it. It's no, I have no problem with a combined with coffee. As you said to energy drinks, I can probably sleep so that I don't know if that's genetics or it's kind of, I don't know what it is, or maybe that I don't have kids, and I'm single. So I don't have, I'm almost listening to some kind of biological signal versus societal signal. I'm where I'm supposed to go to sleep, so I just go to sleep, whatever I feel like
honestly, well, that's cause you're self-employed self-promotion.
Don't have that luxury but we're lucky the two of us that we can make our own hours. Yeah. But yeah, it's super important and those people who have shift work and they really need to change the way that works because they're literally killing those people.
Is there something you could say about the mind and stress in terms of effect on longevity sort of because I don't know if you think about it this way, but
When you talk about the biological machine, it's always these mechanisms that don't are not necessarily directly connected to the brain or the operation of the brain. Like what's the role about stress and happiness and you have the sort of higher cognitive things going on in the brain on longevity,
right? Well, that's a great point that the brain is the center for longevity. Actually, we do know that first off when I'm stressed, I can
Mentally stressed then I can see it in my body. Heart rate hormones? It's clear. That's not true surprise. So you got to work on your brain? First and foremost, if you are totally freaked, out agitated all the time. You will live shorter. I'm certain of it, you know, I keep fish, I'm a big aquarium guy and you can see the difference between the fish. That's having a good time and dominant and one that gets picked on. Yeah.
It just looks like crap, I get it. You don't want to be that the little fish getting picked on if you can help it. So I used to be extremely stressed as a kid. I was a perfectionist very shy. Always worried about being a failure. If I didn't get an A plus you know crying in my bedroom that kind of sad existence I got into my 20s pick. Then in my 30s and realized that's not the way to live. So I've worked very hard to get to this point where I almost never get stressed. Never, there's nothing that I've never gotten angry.
My lab. I've got 20 kids. Sometimes it's like a most of the time. It's like a kindergarten. I haven't lost my temper. I'd probably can't. But at that's intentional and I don't worry about stuff. Millions of dollars, billions of dollars at stake, sometimes keep it cool. It's Only Life were all headed to the same place. Anyway, don't worry about it, but the the answer your question, I think in a better way, if you manipulate the brain of an animal, I'll give an example if we turn on this sort of
In that, I mentioned sore one. We good friend of mine at Wash U scheana. My did this? They up regulate the operator that Gene just in the neurons of the animal, it lived longer. So that's sufficient to extend lifespan. We also know that you can manipulate the part of the brain called the hypothalamus which leeches a lot of chemicals into the body and proteins May most of which we don't know yet. But just changing the inflammation of that little organ or part of the brain is sufficient to
Animals live longer as well. So get your brain in order for us before you tackle. Anything else, I would say.
So you kind of mention this, with the inside tracker, there's ability to take blood measurement and then infer from that bunch of different things about your body, and how you can improve, how you can improve the longevity, and you've also mentioned saliva and more efficient ways to get data.
What does that involve? What's the future of data collection? Yeah. For the human biological system,
right? Well yeah that the issue with with blood is you need someone to take it. It's I'm already prick your finger which hurts. Yes. So you got to have something better so I think the what the future looks like is that you'll spit onto a little piece of paper and stick it in machine. It'll it'll do that for you but we're not there yet. So the intermediate future the that I'm building right now is that you would take a swab
Of the inside of your mouth which is the easiest way to take cells out of your body and just ship them off. Okay. So called a buccal swab I think we became very used to that right right now because of covid people don't like going to the doctor as much. They don't like going out. They just want to have home tests and so that I think is the next 10 years where you'll get a kit in the mail, you'll swab your cheek. Stick it back in an envelope, send send it off. And, you know, a week later you have either a doctor's report or a health recommendation
And what can you get off a cheek swab while you can get anything? You can get hormones, stress levels of stress hormones, blood glucose levels. You can also tell your age reasonably accurately doing that actually quite accurately. And those clocks cannot just tell you how you're doing overtime, but can be used to give you recommendations to slow that process down because some people sometimes are 10 years older biologically than their actual chronological chronological age. I mean, why does it matter how many times the earth going around the Sun? So,
Only because about birthdays, it's how long your body's clock has been ticking and how fast? So I could take a cheek swab from you today. Let's take it back to my lab and within by tomorrow, tell you how old you are, biologically, based on what we call the epigenetic clock, and you might be freaked out. You might be happy, but either way, we can advise you on how to improve the trajectory because we know that smoking increases the speed of that clock. We also know that fasting and people
Who eat the right foods, have a slower clock, without that knowledge, you're Flying Blind. But I like the idea of us while because it's just so easy. We've a lot of us have done something like that for covid test. It's not
a gallon doing the start of Rapid antigen test. So let me see that particular one rapid antigen test. They've been a source of frustration for me because like everybody should be doing it, it's so easy.
We've also been working in my lab on democratizing. These tests to bring them down from a few hundred bucks to a dollar.
So, just to clarify you
Talking about not research, you talk about like company stuff like actual, right facing things.
Well right, the research on bringing the price down his occurred in my lab at Harvard. And then that intellectual property, is being licensed and has been licensed out to a company. Yeah, that that will be consumer-facing so anybody for a small amount of money can do
this. Well, you get subscriber number one upstairs. They think that's a beautiful, beautiful ideas for somebody who maybe I would have been more hesitant about it until
Covid, but haunt us are super easy. I almost wanted to share that data with the world. Like in some way not not the entirety of the data but like some visualization of like how I'm doing. Like it's almost like like you know when you share if you had like a long run or something like that, I wish I could share it because it inspires others and then you can have a conversation about like well what are the hacks that you've tried and have a conversation about like how to improve lifestyle and those kinds of things that's ground.
And
data that's exactly that's what's that's what's going to happen? Note, Everything is anonymous. Of course we talked about security there, but once it's anonymized, you can then plot these numbers and I've plotted my epigenetic age versus hundreds of other people who have taken this test now. And I can tell you where I fit relative to others in terms of my biological age and I'm happy to share that with you all because it's pretty low, you can choose to share it. Of course, not everyone wants to share that, but when you go to the doctor, first of all, you doctors,
It doesn't does treat you as though you're an average person and none of us are average. There's no such thing but second of all, we never know how we're doing relative to others because we all most of us, we don't share our information. So we might have this number and that number. But do you know that your numbers are good for your age or not? You have no idea. Now, even your doctor probably doesn't even know. So this, this graph that I'm talking about, is the beginning of a world where you can say, how am I doing? I'm a for the two of us wear white and we may land.
This age and we do this.
Are we good? Are we doing the right things or the wrong things? Do we need to fix certain things? And this is what the future is it forget about just experimenting and not knowing the result. I mean, who does an experiment and doesn't look at the data, no one. It makes no sense. So, we're going to enter a world where we have a dashboard on our body, the swabs, the blood test, the biosensors, where our doctors can look at that. But we can also look at it and they can recommend go to this restaurant down the road. They've got this great meal, it's high in whatever you need to
Because you're lacking vitamin d and vitamin K2 go for it. Ridiculous question or perhaps not
if you look maybe 50 years from now or a hundred years from now person born then what do you think is a good goal in terms of how long a person would live? What is the maximum longevity that we can achieve through the methods that we have today of or are developing some of the things we've been talking about in terms of genetics, in terms of biology?
Gee what's is there a number?
Right well, so it changes all the time because technology is changing so quickly. I keep revising the number upward, but I would say that if you do the right things during your life and start at an early age, let's say, 25 we don't want malnutrition starvation. That's not what I'm talking about. But in your 20s start eating the kind of diets that I talked about skipping meals in animals, that gives you an extra twenty to thirty percent, we don't know if that's true for humans and that would
Even 5% more would be a good a big deal for the planet. I think that we should all aim to at least reach a century. I'm a little bit behind. I was born too early to benefit the most from all of this discovery, those of you who are in your 20s, you should definitely aim to reach a hundred, I don't see why not consider. This is really important. The average life span of a human that looks after them selves and but doesn't pay attention.
Is about 80, okay? Japan? That's the average age for a male bit higher. If you do the right things in your life which is eat healthy food, don't overeat, don't become obese, do a bit of exercise, get good sleep and don't stress that gives you on. Average 14 extra years that get you to 94. So getting to a hundred, if you just focus on what I'm talking about, it's not a big deal. So what's the maximum while we know that one human made it 222 and a number of the make it into
Teens. I think that's also the next level of where we can get to with the types of technologies that I'm talking about. Medicines, like I mentioned rapamycin, there's one called metformin, which is the diabetes drug, which I take that in combination with these Lifestyle. Changes should get us Beyond a hundred. How long can we ultimately live? Well, there's no maximum limit to human lifespan. Why can a whale live 300 years but we cannot we basically the same structure. We just need to learn from them. So anyone who says,
You Max that max out at X I think is, is full of it. There's nothing that I've seen that says, biological organisms have to die. There are trees that live for thousands of years and their biochemistry is pretty close to ours.
What do you think it means to live for very long time? Let's say if it's 200 years, we're talking about or Thousand Years,
there's some some sense you could argue that there is Immortal organisms already living on Earth, like there's bacteria. So there's certain the certain living organisms that in some fundamental way, do not die because they keep replicating their genetic information. They keep like cloning themselves
Is, is it the same human if we can somehow persist the human mind, like, copy, clone, certain aspects, and just keep replacing pop, body parts. Do you think that's another way to achieve immortality to achieve of a prolonged sort of increased? Longevity is to replace the parts that break easily and keep because actually from your Theory of Aging as a degradation,
Information and information Theory view of Aging like what is what is the key information that makes a human? Can we persist that information and just replaced the trivial Parts?
Yeah, I mean the short answer is yes. We're already replacing body parts but what makes us human is our brain. Everything else is is suboptimal accept our brain. The ability to replace actual neurons is really hard.
I think it might be easy to upload rather than replace your odds because that they're so tight. It's such a network and just perturbing the system, you know, it's it's rotating disk at you, you change everything, once you get in there, the problem is well I guess the solution, let me go to the solution. That's more interesting. What we're learning is that if you reverse the age of nerve cells, they look it looks like they get their Memories Back like so the memories are not lost. Their just that the
Don't how to interpret them and function correctly and this is one of the things we're studying my lab. If you take an old mouse, that has learned something when it was young, but forgotten, does it get that back and all evidence points to that being true? So, I'd rather go in and rejuvenate the brain as it sets rather than replace individual cells which would be really hard.
What do you think about like efforts? They can neural link which basically you mentioned uploading are trying to figure out for creating brain computer interface
Has there trying to figure out how to communicate with the brain, but one of the features of that is trying to record the human brain more and more accurately. Do you have hope for that too? Of course there's a it will lead to us. Better understanding from a neuroscience perspective, the human mind but do you have hope for it increasing longevity? In terms of how it's
used? I think that it can help with certain diseases, but I see at least within our lifetime. That's the
Just use of it is to be able to replace parts of the body that are not functioning such as the retina and other parts. The visual cortex back here that that's going to be doable in terms of longevity and maybe we could put something on the hypothalamus and start secreting those hormones and get that back. Ultimately I think it's the best way to preserve the brain. Is going to be to record it but also I think it's going to require death unfortunately.
Lee to then do very detailed scans. Even if you have enough time and money, Atomic microscopy, and rebuild, the brain from
scratch, vehicle from scratch. Here we are living more and more in digital world. I wonder if the scanning is good enough for the critical things in terms of memories, in terms of the particular quirks of your cognitive
processes. They're not, they're not end.
Yeah, we're not we're not close. Yes, but we've
Quite a bit of progress. So it's if you're if you're an exponential type of person.
Yeah. Well, let's Dream a Little hear us. That's the way it would work that I could see it working is. So you take a single cell slice through your dead brain, and we can. Now the problem, the problem with the engineering aspect is that the engineering is the physical aspect of the brain, is not even half the problem. The problem is, which genes are switched on and off this,
Experience that we're having here is is altering certain genes in neurons that will be preserved hopefully for a number of decades but you cannot see that with a microscope easily but there are Technologies. Different invented actually just down the hole in the building. I'm at George Church invented away. His lab invented a way to look at which genes are switched on and off, not only in a single cell, which any lab can do these days but in situ where it's situated in the brain. So you
Okay. This nerve cell had these genes switched on and these Switched Off we can recreate that but just scanning the brain and looking how the nerves are touching? Each other is not going to do it.
Wow. Okay, so you have to scan the full biology, the full details. Look at the epigenome at the epigenome
to. Yeah, which genes are on and off. It's just easier to reset the epigenome and get them to work. Like they used to use. We're doing that. Now, use the hardware already have
just figure out how to make that Hardware last longer,
right? Ultimately information will be lost even genetic information, degrade slowly through mutation. So we immortality is not achievable through that means that I think we could potentially
Reset the body hundreds of times and live for thousands of years.
Okay, so we talked about biology, let's forgive me but let's talk about Philosophy for just a brief moment. So somebody I've enjoyed reading Ernest, Becker wrote the denial of death. There's also Martin Heidegger there's a bunch of philosophers who claim that most people live life in denial of death sort of we
Don't fully internalize the idea that we're going to die. The
Because if we did as they say, there will be a kind of Terror of. I mean, a deep fear of death, the fact that we don't know what's like we almost don't know what to do with non-existence with disappearing like
our the way we draw,
meaning from life seems to be grounded in the fact that we exist and that we some point.
Not exist is terrifying and so we live in an illusion that we're not going to die and we would run from that Terror. That's what Earnest backward. Say, do you think there's any truth to
that? Oh I know this truth to that. I experience it every day when I talk to people, we have to live that way. Although unfortunately, I can't, but for most people it's extremely distressing distressing to think about their own mortality. We think about it occasionally, and if we really thought about it every day,
We'd probably be brought to tears how much weed. Not just miss ourselves but miss our family, our friends, we are all living life forms have evolved to to not want to die. And when I mean want by chemically genetically physically that yeast cell the cells that I studied at MIT they were fighting for their lives. They didn't think but our brain has evolved the same survival aspect. Of course, we don't want to die but the problem for us unfortunately,
It's a curse. And a blessing is the way now. Conscious we know that we're going to die. Most species that have ever existed. Don't that's a bird and that's a curse. And so, what I think's happened is we've evolved certainly to want to live for a long time, perhaps never want to die. But the thought about dying is so traumatic that there is an innate part of our brains and it's probably genetically wired to not think about it. I really think that's part of being
Human and it because, you know, I think about tribes that obsessed with longevity every day and that we're going to die. They probably didn't make much technological progress because they were just crying in their Huts every day or, you know, on the Savannah. So I really think that we've evolved to naturally deny aging and it's one of the problems that I faced in my career and, you know, when I speak publicly and on social media is that it's shocking. People don't want to think about their age, but I think it's getting better. I think my
My book has helped these tests that were developing should help people understand. It's not a problem to think about your long-term Health. In fact, if you don't, you're going to reach 80 and really regret it
and the other side of it. So, again, Ernest Becker. But also Viktor Frankl recommend a highly Man's Search for meaning, Bernard Williams is a moral philosopher. They kind of argue that this knowledge of death, even if we often don't contemplate it,
We do at times and the very well you called The Curse, which I agree with you. It's a, it's a curse and a blessing that we're able to contemplate our own mortality, that gives meaning to life. So death gives meaning to life as what, Victor Frankel's argues, I would probably argue the same. There's something about the scarcity of life, and contemplating, that, that makes each moment that much sweeter. Is there something to that?
I think it's individual in my case it's completely wrong I appreciate you saying that, I don't get joy out of every day because I think I'm going to die. Yeah I get joy out of every day because every day is joyous and I make it that way. And even if I would, if I thought I was going to live forever, I would still be enjoying this moment just as much.
And I bet you would too. Well, that's a
I think about that a lot. I think it's very difficult to know, I'm almost afraid that. I wouldn't enjoy it as much if I was Immortal. I'm almost afraid to want to be immortal or to live longer because it perhaps is a kind of justification for me to accept that. I'm going to die is saying like, oh, if I was a morte, I wouldn't be able to enjoy.
Life as much as I do, but it's very possible that I would enjoy just as much.
Of
course, enjoying life, whether you're mortal or not takes work, like it requires you to have the, right? Kind of frame of mind. You can discover, you can focus your mind on the ugliness of life. There's plenty of ugly things in this world and you can focus on them. You can complain whenever like, you know, if it's raining outside, you can
you can focus on the fact that you have shelter and enjoy the hell out of it, or you can enjoy running in the rain when it's warm and like the the beauty of nature just being one with nature or you can just complain this fucking weather again in Boston and then redo their always raining or freezing damn it and like the the same, the same thing with like, Wi-Fi, going out on airplanes. Like you can either complain about like,
stupid Wi-Fi and
Dead blue or something? Or you could
say like how incredible it is that I can fly through the
sky in a matter of hours, be anywhere else in the
world and that it could also on occasion watch like check email and even watch movies through the while connecting through satellites that are flying through space. So it's a matter of perspective and perhaps there's an extra level of work required when you're Immortal because it's easier when you're Immortal or let live longer to to be lazy to delay stuff. But if you're not,
You can still derive the same out of Joy. It's possible. It's possible.
It's definitely possible in my life. I went from being the nothing's working to every day is great. We have to wake up to and I think even if you live think you can live forever you can you can enjoy every day. What I do is Everything's Relative, we can compare ourselves to our neighbor who has more money or to the flight that should have had Wi-Fi or which is what I do. I'm still six years old. Remember what a
Does says, look I can, when I tell my fingers to form a fist, they actually do that. That's really cool. That's how I live my life, your, I'm I can pick up on your desk here. This metal object, it's a metal cube about an inch by inch by an inch. And I I tell myself not, not about Cubes, but about inanimate objects. Probably once a day, I'll say,
I am a living thing. I can think I can move. I can eat. I am full of energy and there's that leaf or this Cube here that will never be alive. That's what I look at and compare myself to and for as long as I live if it's forever, of course it won't be. But even if it was forever, the relative to this lump of metal on this table, here we are wondrous things in the universe and probably the most wondrous things in the
universe. There were able to deeply appreciate the leaf.
Are the cube and deeply appreciate ourselves. Which is, it can be a curse but it's mostly gift, especially when you're such a beautiful Palm. Now, I'm six. I'm as clever as clever. So I think I'll be six now forever and ever. It's a good thing to Aspire to your your grandmother was on to something David. This is incredible conversation. I'm a huge fan of your work. So thank you for wasting your valuable.
Double time
with me today. I really, really appreciate this was
awesome. Thank you for having me on like
appreciate it.
Thanks for listening to this conversation with David Sinclair. A thank you to on it. Clear National instruments Simply Safe and linode check them out in the description to support this podcast. And now let me leave you with some words from Arthur schopenhauer all truth passes through three stages. First it is ridiculed. Second it is violently opposed third. It is accepted as being self-evident. Thank you for listening and hope to see
You next time.
