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EPISODE LINKS:
David's Twitter: https://twitter.com/davidasinclair
David's Website: https://lifespanbook.com

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OUTLINE:
0:00 - Introduction
1:34 - Staying young at heart
5:30 - Bringing people back to life
11:05 - Wearables and tracking health data
20:18 - How to solve aging
30:22 - Why do we age?
35:50 - Genetic reset switch that reverses aging
38:20 - AI in biology
40:52 - Health data
48:58 - Fasting
56:29 - Diet
1:04:40 - Exercise
1:10:01 - Sleep
1:18:29 - Data
1:24:00 - Extending lifespan
1:26:42 - Immortality
1:32:28 - Denial of death
1:35:45 - Meaning of life without death

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The following is a conversation with David Sinclair.

He's 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, Onnit, Clear, National Instruments, and I, SimpliSafe, and Linode.

Check them out in the description to support this podcast.

As a side note, let me say that longevity research challenges us to think how science and engineering will change society.

Imagine if we can live 100,000 years, even under controlled conditions, like in a spaceship, say, then suddenly a trip to Alpha Centauri that is 4.37 light years away takes a single human 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 are as exciting of a journey as I could imagine.

This is the Lex Friedman Podcast and here is my conversation with David Sinclair.

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 at 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 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.

12 year olds and even younger, I would say 6, 7 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 six-year-old, because I am that mentally.

But on the other hand, I'm getting older.

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 grownup and be mature, but I definitely don't feel

There's something I really appreciated in the opening of your book.

And on this kind of theme, on this kind of topic, she first of all had a big influence on you.

My grandmother had a big influence on me.

And you also mentioned this poem by the author of Winnie the Pooh, Alan Alexander Milne.

Maybe I can read it real quick, because I love, on the topic of being children, when I was 1, I had just begun.

When I was 5 I was just alive but now I am 6.

I am as clever as clever so I think I'll be 6 now forever and ever." So this idea of being 6 and staying 6 forever, being youthful, being curious, being childlike, 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 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 1 of those people that wouldn't talk about the little things.

Don't talk to me about politics or the weather.

Yeah, talk to me about human beings and culture.

And this poem was 1 that she read to me often because she knew that 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 and 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 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, 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.

That's what I get up in the morning to do, is to leave the world a better place and show to whoever's 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 artificial intelligence.

I don't know if you've seen videos of basically animating people back to life.

Meaning whether it's, for me personally, I've been working on specifically about Albert Einstein, but also Alan Turing, Isaac Newton, and Richard Feynman.

And it's an opportunity to bring people that meant a lot to 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 full richness of character that they had as they struggle with the ideas of the modern age.

Sort of 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, it's using the textual, the visual, 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, there's Replica, which is a chat engine that was born out of the idea of bringing, the founder lost her friend to, 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 a machine learning, natural language system on the texts that they exchanged with each other and she had a conversation with him sort of after he was gone.

It was obvious that it's, you know, AI agent, but it gave her solace.

And that's the way I wonder if it's possible to bring back people that are, that mean 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.

There's a great Black Mirror episode about the wife who brings back the boyfriend or husband.

I think 1 of the challenges with bringing back Richard Feynman would be to capture his sense of humor, but that would be awesome.

But yeah, bringing back loved ones would be great, especially if they're young and they die 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 gonna 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 1 day, everything we see can be recorded.

And then you can build somebody's experience and thoughts, speech, and you will have replicas of everybody, at least digitally, and physically you could do that too 1 day, but 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.

1 person I'd love to meet is Benjamin Franklin.

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 just see the look on his face as to where humanity has come.

Because I think of him as a modern guy that just was before his time.

Yeah, so you're thinking Benjamin Franklin is a scientist, not Benjamin Franklin the political thing.

Because he'd be very upset with Congress right now.

So maybe talk to him about science and technology, 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 personalities are like.

Isaac Newton, it does seem complicated to figure out what their personality is like.

Even Friedrich Nietzsche, who I also thought about.

Feynman is, we just have enough video where we get the full kind of, I mean, it 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.

You mentioned collecting data about a person, collecting the whole thing, the whole of life, the ups and downs, the embarrassing stuff, the beautiful stuff, not just the things that's condensed into a book.

And then with Feynman, 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, 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.

That it feels like it makes you realize how the upside, how nice it is to collect data about a person, to capture that person.

That's the upside of the modern internet age, the digital age, that that information, yeah, creates a kind of immortality.

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've 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 the whole thing.

What's most exciting to you in terms of collecting the biological data about a human being?

I find animals and humans as machines very interesting.

It's 1 of the reasons I didn't become an engineer or a surgeon, I wanted to understand how we actually are 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 Lifespan, 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 wouldn't go to the doctor and they don't know if you need an antibiotic or not.

Long-term, how old are you, how to fix things, what should you eat, what should you take, what should your doctor do?

These devices, I predicted, would be smarter, better educated than your physician, and would augment them, and then there'd be a human that would just tick off to see if 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 pills that were synthesized or delivered in your kitchen and combined certainly.

What's amazing about that is that, what are we now, 2 years since the book came out, even less.

And that future is basically here already.

So where we're at now in society is, if you wanna 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 cheaply for less than $100 now.

I wear this ring from Aura that I have a 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 have 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 measures 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 if I really work at it, I can get my biochemistry down to early to mid 30s.

Though I like to now eat a little dessert once in a while.

But in the very near future, just in the next few years, you can be wearing wearables.

So I'm currently wearing a little, what's called a bio sticker.

It's about an inch long, a few millimeters.

Yeah, for people just listening, it's on David's chest.

Yeah, so on 1 side you have an on button that you press.

The lights come on, flashes 4 times, it's good to go.

And this 1, it's called a BioButton, nice name.

And there's another 1 that I have that I haven't tried yet that does EKG on your heart.

This is mainly for doctors to monitor patients that 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.

But ultimately, what I'm excited about is a future that isn't that far off where everybody, certainly in 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 you an idea what this is measuring me at a thousand times a second is my vibrations as I speak, my orientation.

It already has told me this morning how I slept, where I slept, what side I slept on.

We've got sneezing, coughing, body temperature, heart rate, heart, 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 that 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 gonna 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.

can talk a little bit about InsideTracker because I saw that 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.

So we're not just talking about diseases, right?

Like anticipating having a particular disease, but it's almost like guiding your trajectory to life, how to, whether it's extend your life or just live a more fulfilling, like improve the quality of life, I suppose this is the right way to say it.

Because I thought the results were pretty cool.

It's like a company, consumer-facing company?

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.

But for now it's a blood test and you'd go to a lab core request in the US.

You can upload your own data for 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 in terms of health and longevity at bio age, they call it, no, inner age.

It sounds like it might be to say, oh, go eat this or go to that restaurant and order that.

But it's actually based on This company has entered hundreds, now it would be thousands of scientific papers into their database, and hundreds of thousands of human data points.

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.

And I was 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.

The 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 whatever the scientific paper is to make the suggestion of how that work applies to your life and that ultimately maps to a recommendation of what you should do with your life.

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.

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 checkup and having males get a finger up their butt and you cough, That to me is a joke, that's medieval medicine.

And that's very soon going to be seen as medieval.

Yeah, to me as a computer science person, it's always upsetting to go to the doctor and just look at him and realize you know nothing about me.

You're making your opinions based on, it is very valuable, years of intuition building about basic symptoms, but you're just like, it is medieval.

In fact, doctors in Medieval times were 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.

So I'm not against the profession at all.

But I think that they need just as much help as anyone else does.

We wouldn't drive a car without a dashboard.

If we could, can we step back to the big, profound, philosophical, both tragic and beautiful question about age?

Is it, From an engineering perspective, you said you like the biological machine.

Is that a feature or a bug of the biological machine?

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 live 2 and a half years, 3 years.

You're probably going to die of starvation, predation, freezing in the winter.

So they divert most of their 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, a bowhead whale in 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 breed slowly and build a body that lasts.

We're somewhere in between because we've really only just come out of the savannas where we could be picked off by a cat.

We were pretty wimpy going back 6000000 years ago.

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.

These arms, if any of us, even the strongest person in the world went in a cage with a chimpanzee, The chimp could knock that person's head off, no question.

So we need to engineer ourselves to be healthier and longer lived.

So getting to aging, we can do better, right?

We're trying to learn how whales do that.

And If you ask really anybody in the field now, professor, they'll say there are 8 or 9 hallmarks of aging, which are really, it's a word for causes of aging.

So you probably have heard of some of these.

Your listeners will have loss 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 become, they put out what are called mitogens that cause cancer and inflammatory molecules.

That's another aspect of aging, cellular senescence.

Another 1 is loss of the energetics, so mitochondria, the battery packs wind down.

There's a whole bunch, stem cells, proteostasis.

Well, these are our Achilles heels that I'm talking about, that are common amongst all life forms, really.

But if you want me to jump to the chase as to where, what is the upstream defining factor?

So most biologists would say you can't boil it down, it's too complex.

I would say you can boil it down to an equation, which is the preservation of information and lost due to entropy, i.e.

It originally came out of discoveries in yeast cells where I went to MIT in the 1990s.

I studied the makers of bread, a little yeast called Saccharomyces cerevisiae, which at the time was 1 of the hottest, excuse the pun, organisms to work on.

But we figured out in the lab why yeast cells get old and found genes that control that process and made them live longer, which was an amazing 4 years of my life.

1 of those genes had a name with an acronym SIR2.

The SIR is important, and the most important letter out of all of those 3 is I, which stands for information.

Silent information regulator number 2, when you put more copies of that gene in, just put in 1 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 in humans and mice, because they live shorter and cheaper to study, where the loss of information in our bodies is a root cause of aging, and I think it is.

Your boldness in viewing biology in this way is fascinating because that also leads to a kind of, it's almost like allows for a theory of aging, like you could boil it down to a single equation and it leads to perhaps a metric that allows you to optimize aging, sort of in the fight against entropy.

I had to figure out which mechanisms, like you said, the silent information regulator, which mechanisms allow you to preserve information without injecting noise, 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 amenable 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, the degradation of that information.

Right, so we have some information regulator genes in our bodies, we have 7 of them, SIRT1 through 7 they're called, And we found in mice, 1 way to slow down the loss of information is to just give more of these, to upregulate these genes.

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David Sinclair: Extending the Human Lifespan Beyond 100 Years | Lex Fridman Podcast #189