David Sinclair: Extending the Human Lifespan Beyond 100 Years #189

Transcript

00:00:00 The following is a conversation with David Sinclair.

00:00:02 He’s a professor in the Department of Genetics at Harvard

00:00:06 and co director of the Paul F. Glenn Center

00:00:08 for the Biology of Aging at Harvard Medical School.

00:00:12 He’s the author of the book,

00:00:13 Lifespan and co founder of several biotech companies.

00:00:16 He works on turning age into an engineering problem

00:00:20 and solving it.

00:00:22 Driven by a vision of a world

00:00:23 where billions of people can live much longer

00:00:25 and much healthier lives.

00:00:28 Quick mention of our sponsors,

00:00:30 Onnit, Clear, National Instruments,

00:00:33 and I, SimpliSafe and Linode.

00:00:36 Check them out in the description to support this podcast.

00:00:40 As a side note, let me say that longevity research

00:00:42 challenges us to think how science and engineering

00:00:45 will change society.

00:00:47 Imagine if we can live 100,000 years,

00:00:50 even under controlled conditions,

00:00:51 like in a spaceship say,

00:00:53 then suddenly a trip to Alpha Centauri

00:00:55 that is a 4.37 light years away

00:00:58 takes a single human lifespan.

00:01:01 And on the psychological, maybe even philosophical level,

00:01:05 as the horizons of death drifts farther into the distance,

00:01:08 how will our search for meaning change?

00:01:11 Does meaning require death

00:01:13 or does it merely require struggle?

00:01:15 Reprogramming our biology will require us to delve deeper

00:01:19 into understanding the human mind and the robot mind.

00:01:23 Both of these efforts are as exciting of a journey

00:01:26 as I can imagine.

00:01:28 This is the Lex Friedman Podcast

00:01:30 and here is my conversation with David Sinclair.

00:01:34 I usually feel like the same person when I was 12.

00:01:38 Like when I, right now, as I think about myself,

00:01:42 I feel like exactly the same person

00:01:45 that I was when I was 12.

00:01:46 And yet, I am getting older, both body and mind,

00:01:51 and still feel like time hasn’t passed at all.

00:01:54 Do you feel this tension in yourself

00:01:56 that you’re the same person and yet you’re aging?

00:02:01 Yeah, I have this tension that I’m still a kid,

00:02:04 but that helps in my career.

00:02:05 Scientists need to have a wonder about the world

00:02:07 and you don’t wanna grow up at 12 year olds

00:02:10 and even younger, I would say six, seven year olds.

00:02:13 I’ve still got that boy in me and I can look at things.

00:02:16 It’s a gift, I think, that I can see things

00:02:18 for the first time if I choose to,

00:02:19 and then explain them as I would to a six year old

00:02:23 because I am that mentally.

00:02:24 But on the other hand, I’m getting older, right?

00:02:26 I run a lab of 20 people at Harvard.

00:02:29 I’ve got a book, I’ve got science to do, companies to run,

00:02:33 and so I have to, on most days,

00:02:35 just pretend to be a grownup and be mature,

00:02:38 but I definitely don’t feel that way.

00:02:40 There’s something I really appreciated

00:02:43 in opening your book.

00:02:44 You talked about your grandmother.

00:02:46 And on this kind of theme, on this kind of topic,

00:02:51 she, first of all, had a big influence on you.

00:02:53 My grandmother had a big influence on me.

00:02:57 And you also mentioned this poem

00:02:59 by the author of Winnie the Pooh, Alan Alexander Milne.

00:03:04 Maybe I can read it real quick

00:03:06 because I love, on the topic of being children,

00:03:10 when I was one, I had just begun.

00:03:12 When I was two, I was nearly new.

00:03:14 When I was three, I was hardly me.

00:03:17 When I was four, I was not much more.

00:03:19 When I was five, I was just alive, but now I am six.

00:03:24 I am as clever, as clever, so I think I’ll be six,

00:03:27 now, forever and ever.

00:03:31 So this idea of being six and staying six forever,

00:03:37 being youthful, being curious,

00:03:39 being childlike, this and other things,

00:03:43 what influence has your grandmother had

00:03:46 in your thinking about life, about death, about love?

00:03:53 Yeah, I was getting misty eyed as you read that

00:03:54 because that poem was read to me very often,

00:03:58 if not every day, by my grandmother,

00:03:59 who partially raised me.

00:04:02 And she was as much a bohemian as an artist, philosopher.

00:04:06 And she’s one of those people

00:04:08 that wouldn’t talk about the little things.

00:04:09 She said, I hate small talk.

00:04:11 Don’t talk to me about politics or the weather.

00:04:13 Yeah, talk to me about human beings and culture.

00:04:16 So I was raised on that,

00:04:18 and this poem was one that she read to me often

00:04:20 because she knew that the mind of a child is precious,

00:04:26 it’s honest, it’s pure.

00:04:28 And she grew up during the Second World War

00:04:31 and in Hungary and Budapest witnessed the worst of humanity.

00:04:35 She was trying to save a whole group of Jewish friends

00:04:40 in her apartment, saw what happened after the World War,

00:04:43 which was there was, the Russians were in control

00:04:47 and locals weren’t necessarily treated well

00:04:50 if they were rebellious, which she was.

00:04:52 And then there was the revolution in 56,

00:04:54 which she was part of and had to escape the country.

00:04:57 So she saw what can happen when humans do their worst.

00:05:01 And her words to me, expressed in part through that poem

00:05:05 was, David, always stay young and innocent

00:05:09 and have wonder about the world,

00:05:11 and then do your best to make humanity the best it can be.

00:05:15 And that’s who I am, that’s what I live for,

00:05:18 that’s what I get up in the morning to do

00:05:19 is to leave the world a better place

00:05:21 and show to whoever’s watching us,

00:05:23 whether it’s aliens or some future human historian,

00:05:26 that we can do better than we did in the 20th century.

00:05:31 You know, we mentioned offline this idea

00:05:33 of bringing people back to life

00:05:34 through artificial intelligence,

00:05:38 sort of, I don’t know if you’ve seen videos

00:05:40 of basically animating people back to life,

00:05:45 meaning whether it’s, for me personally,

00:05:47 I’ve been working on specifically about Albert Einstein,

00:05:51 but also Alan Turing, Isaac Newton, and Richard Feynman.

00:05:56 And it’s an opportunity to bring people

00:05:59 that meant a lot to others in the world

00:06:02 and animate them and be able to have a conversation

00:06:06 with them at first to try to visually,

00:06:12 visually explore the full richness of character

00:06:17 that they had as they struggle

00:06:18 with the ideas of the modern age.

00:06:20 Sort of, it’s less about bringing back their mind

00:06:24 and more bringing back the visual quirks

00:06:27 that made them who they are.

00:06:28 And then maybe in the future,

00:06:30 it’s using the textual, the visual,

00:06:33 the video, the audio data to actually compress

00:06:38 down the person for who they are

00:06:41 and be able to generate text.

00:06:42 There’s a few companies, there’s Replica,

00:06:44 which is a chat engine that was born

00:06:46 out of the idea of bringing,

00:06:48 the founder lost her friend to,

00:06:53 he got run over by a car.

00:06:55 And the initial reason she founded the company

00:06:59 was trying to just have a conversation with her friend.

00:07:02 She trained machine learning, natural language system

00:07:07 on the texts that they exchange with each other

00:07:09 and try, she had a conversation with him

00:07:11 sort of after he was gone.

00:07:13 And it’s very, the conversation was very trivial.

00:07:16 It was obvious that it’s AI agent,

00:07:21 but it gave her solace.

00:07:23 It made her actually feel really good.

00:07:26 And that’s the way I wonder if it’s possible

00:07:27 to bring back people that are,

00:07:30 that mean something to us personally,

00:07:32 not just Einstein, but people that we’ve lost

00:07:36 and in that way achieve a kind of small

00:07:40 artificial immortality.

00:07:42 I don’t know if you think about this kind of stuff.

00:07:44 Well, I definitely think about a lot of things.

00:07:46 That one’s a really good one.

00:07:47 There’s a great Black Mirror episode

00:07:49 about the wife who brings back the boyfriend or husband.

00:07:52 I think one of the challenges

00:07:54 with bringing back Richard Feynman

00:07:55 would be to capture his sense of humor,

00:07:58 but that would be awesome.

00:07:59 But yeah, bringing back loved ones would be great,

00:08:00 especially if they’re young and they die early,

00:08:07 though it may hold you back from moving on.

00:08:09 That’s another thing that could happen as a negative.

00:08:11 But I think that’s great.

00:08:12 And I also think that it’s gonna be possible,

00:08:14 especially when we’re recording some of us,

00:08:17 every aspect of our lives,

00:08:18 whether it’s our face or things we see, right?

00:08:22 Eventually one day, everything we see can be recorded.

00:08:26 And then you can build somebody’s experience

00:08:28 and thoughts, speech,

00:08:31 and you will have replicas of everybody,

00:08:35 at least digitally,

00:08:36 and physically you could do that too one day.

00:08:38 But that’s a good idea,

00:08:40 especially because there are people that I’d like to meet,

00:08:42 and I think it’s easier than building a time machine.

00:08:44 One person I’d love to meet is Benjamin Franklin.

00:08:47 Really?

00:08:48 Well, I wouldn’t go back in time.

00:08:50 I would, but I’d prefer to bring him into the future

00:08:53 and say, can you believe we have this thinking machine

00:08:57 in our pockets now?

00:08:58 And just see the look on his face

00:09:00 as to where humanity has come.

00:09:01 Because I think of him as a modern guy

00:09:03 that just was before his time.

00:09:05 Yeah, so you’re thinking Benjamin Franklin the scientist,

00:09:08 not Benjamin Franklin the political thing.

00:09:10 Because he’d be very upset with Congress right now.

00:09:13 Right.

00:09:13 So maybe talk to him about science and technology,

00:09:16 not politics.

00:09:18 Or maybe just don’t get him on Twitter

00:09:19 because he’ll be very upset with human civilization.

00:09:22 You know, I wonder what their personalities are like.

00:09:25 Isaac Newton, it does seem complicated

00:09:28 to figure out what their personality is like.

00:09:30 Even Friedrich Nietzsche, who I also thought about.

00:09:33 Feynman is, we just have enough video

00:09:36 where we get the full kind of,

00:09:39 I mean, it shows you how important it is

00:09:42 to get not the official kind of book level presentation

00:09:47 of a human, but the authentic,

00:09:49 the full spectrum of humanity.

00:09:51 You mentioned collecting data about a person,

00:09:54 collecting the whole thing, the whole of life,

00:09:57 the ups and downs, the embarrassing stuff,

00:09:59 the beautiful stuff, not just the things

00:10:01 that’s condensed into a book.

00:10:03 And then with Feynman, you start to see that a little bit.

00:10:05 Through conversations, you start to see peaks

00:10:07 of like that genius.

00:10:09 And then through stories about him from others.

00:10:12 And then certainly you, the sad thing

00:10:15 about Alan Turing, for example,

00:10:17 is there’s very little, if any, recording of him.

00:10:22 In fact, I haven’t been able to find recording

00:10:24 allegedly there’s supposed to be a recording of him

00:10:27 doing some kind of a radio broadcast,

00:10:29 but I haven’t been able to find anything.

00:10:32 And so that’s truly sad that it feels like

00:10:35 it makes you realize how the upside,

00:10:40 how nice it is to collect data about a person,

00:10:44 to capture that person.

00:10:46 That’s the upside of the modern internet age,

00:10:48 the digital age, that that information,

00:10:51 yeah, creates a kind of immortality.

00:10:55 And then you can choose to highlight

00:10:57 the best parts of the person,

00:10:58 maybe throw away the ugly parts

00:11:00 and celebrate them even after they’re gone.

00:11:03 So that’s a really interesting opportunity.

00:11:05 You’ve also mentioned to me offline

00:11:07 that you’re really excited about all the different wearables

00:11:11 and all the different ways we can collect information

00:11:14 about our bodies, about the whole thing.

00:11:18 What’s most exciting to you in terms of collecting

00:11:21 the biological data about a human being?

00:11:27 Well, so I’m a biologist.

00:11:29 I find animals and humans as machines very interesting.

00:11:34 It’s one of the reasons I didn’t become an engineer

00:11:36 or a surgeon.

00:11:37 I wanted to understand how we actually are built.

00:11:40 And so I think a lot about machines merging with humans.

00:11:46 And the first of that are the bio wearables.

00:11:49 And so I talked a lot about this, I wrote about it

00:11:51 in Lifespan, the book, and pictured a future

00:11:54 where you would be monitored constantly

00:11:56 so that you wouldn’t suddenly have a heart attack,

00:11:59 you’d know that was coming,

00:12:00 or you wouldn’t go to the doctor

00:12:02 and they don’t know if you need an antibiotic or not.

00:12:07 Long term, how old are you, how to fix things,

00:12:09 what should you eat, what should you take,

00:12:11 what should your doctor do?

00:12:12 These devices, I predicted, would be smarter,

00:12:16 better educated than your physician

00:12:18 and would augment them.

00:12:19 And then there’d be a human that would just tick off

00:12:21 to see if it’s correct and they approve.

00:12:24 I also was predicting in the book

00:12:26 that we would have video conferences with our doctors

00:12:30 and that medicines would be delivered,

00:12:32 initially by courier, but eventually by drones

00:12:33 and get it to you sometimes in an emergency.

00:12:36 And that we could even have pills

00:12:37 that were synthesized or delivered in your kitchen

00:12:41 and combined certainly.

00:12:43 What’s amazing about that is that, what are we now,

00:12:47 two years since the book came out, even less,

00:12:50 and that future is basically here already.

00:12:52 COVID 19 accelerated that incredibly.

00:12:56 So where we’re at now in society is,

00:12:58 if you wanna pay for it, you can have a blood test

00:13:00 that will detect cancer 10, 20 years earlier than it would

00:13:03 before it forms a tumor.

00:13:05 You can, of course, do your genome very cheaply

00:13:07 for less than $100 now.

00:13:10 There are bio wearables already I wear,

00:13:12 this ring from Aura that I have a number of years of data.

00:13:17 I’ve been doing blood tests for the last 12 years

00:13:19 with a company called Inside Tracker, which I consult for.

00:13:22 And so I have all of that data as well.

00:13:24 And there’s 34 different parameters on my testosterone,

00:13:27 my blood glucose, my inflammation.

00:13:30 And I use all that data to, of course,

00:13:32 I wear a watch that measures things as well.

00:13:34 I use that data to keep my body in optimal shape.

00:13:39 So I’m now 51.

00:13:40 And according to those parameters,

00:13:42 I’m at least as good as someone in their early 40s.

00:13:45 And if I really work at it,

00:13:47 I can get my biochemistry down to early to mid 30s,

00:13:52 though I like to now eat a little dessert once in a while.

00:13:56 So that’s the future we’re in right now.

00:13:58 Anyone can do what I just said.

00:14:00 But in the very near future, just in the next few years,

00:14:04 you can be wearing wearables.

00:14:06 So I’m currently wearing a little,

00:14:08 what’s called a bio sticker.

00:14:10 This one I just put on last night.

00:14:14 It’s about an inch long, a few millimeters.

00:14:18 Yeah, for people just listening, it’s on David’s chest.

00:14:21 It’s just, how does it attach?

00:14:23 It’s just kind of.

00:14:24 It sticks on. Sticks on.

00:14:25 Yeah, so on one side you have an on button that you press.

00:14:27 The lights come on, flashes four times, it’s good to go.

00:14:30 It immediately syncs to your phone.

00:14:32 And this one, it’s called a bio button, a nice name.

00:14:37 And there’s another one that I have that I haven’t tried yet

00:14:39 that does EKG on your heart.

00:14:41 This is mainly for doctors to monitor patients

00:14:43 that go home after a heart attack or surgery.

00:14:45 But that’s medical grade FDA approved device.

00:14:48 So there will be a day, in fact, it’s already here,

00:14:51 that doctors are using these to get patients to go home

00:14:55 and save a week in hospital, $2,000 at least

00:14:59 for each patient.

00:15:00 That’s massive savings for the hospital.

00:15:04 But ultimately what I’m excited about is a future

00:15:06 that isn’t that far off where everybody,

00:15:10 certainly in developed countries,

00:15:11 eventually these will cost a few cents and rechargeable.

00:15:14 The only cost will be the software subscription

00:15:16 that can be monitored constantly.

00:15:19 And to give an idea what this is measuring me

00:15:21 at a thousand times a second is my vibrations as I speak,

00:15:26 my orientation, it already has told me this morning

00:15:29 how I slept, where I slept, what side I slept on.

00:15:33 We’ve got sneezing, coughing, body temperature,

00:15:37 heart rate, heart of other parameters of the heart

00:15:40 that would indicate heart health.

00:15:44 These data are being used to now to predict sickness.

00:15:49 So eventually we’ll have just in the next year or so

00:15:53 the ability to predict whether something

00:15:55 or diagnose whether something is pneumonia

00:15:58 or just a rhinovirus that can be treated or not.

00:16:02 This is really going to not just revolutionize medicine,

00:16:06 but I think extend lives dramatically.

00:16:08 Because if I’m gonna have a heart attack next week

00:16:11 and that’s possible, this device should know that

00:16:14 and I’ll be in hospital before I even have it.

00:16:16 Maybe you can talk a little bit about InsideTracker

00:16:19 because I saw that there’s some really cool things in there.

00:16:23 Like it actually, so maybe you can talk about,

00:16:25 I guess that you’re collecting blood to give it the data.

00:16:29 So, and it has like basic recommendations

00:16:32 on how to improve your life.

00:16:34 So we’re not just talking about diseases, right?

00:16:36 Like anticipating having a particular disease,

00:16:39 but it’s almost like guiding your trajectory to life,

00:16:41 how to, whether it’s extend your life

00:16:44 or just live a more fulfilling,

00:16:46 like improve the quality of life.

00:16:48 I suppose this is the right way to say it.

00:16:50 How does InsideTracker work?

00:16:52 What the heck is it?

00:16:53 Because I thought there was also pretty cool.

00:16:55 Yeah.

00:16:55 What is it?

00:16:56 Is it something other people can use?

00:16:58 You can definitely use it.

00:16:59 You can sign up, it’s consumer.

00:17:02 It’s like a company consumer facing company.

00:17:04 It is, yeah.

00:17:06 And I also want to democratize the ability

00:17:08 to just take a mouth swab eventually.

00:17:11 We don’t need to have a blood test necessarily,

00:17:13 but for now it’s a blood test

00:17:14 and you’d go to a lab core request in the US.

00:17:18 It’s also available overseas.

00:17:19 You can upload your own data for a minimal cost

00:17:22 and get the algorithms, the AI in the background

00:17:26 to take that data,

00:17:27 plot where you are against others in your age group

00:17:31 in terms of health and longevity at bio age.

00:17:34 They call it inner age,

00:17:36 but also it provides recommendations.

00:17:38 And this isn’t just a bunch of BS.

00:17:39 It sounds like it might be to say, I’ll go eat this

00:17:42 or go to that restaurant and order that,

00:17:44 but it’s actually based on the basic.

00:17:47 This company has entered hundreds.

00:17:49 Now it would be thousands of scientific papers

00:17:51 into their database

00:17:53 and hundreds of thousands of human data points.

00:17:55 And they have tens of thousands of individuals

00:17:59 that have been tracked over time

00:18:00 and anonymously that data is used to say

00:18:02 what works and what doesn’t.

00:18:04 If you eat that, what works?

00:18:05 If you take that supplement, what works?

00:18:07 And I was a coauthor on a paper that showed

00:18:09 that the recommendations for food and supplements

00:18:15 was better than the leading drug for type two diabetes.

00:18:18 That’s so cool.

00:18:19 The idea that you can connect,

00:18:21 like skipping the human having to do this work,

00:18:24 you can connect the scientific papers,

00:18:27 almost like meta analysis of the science

00:18:30 connected to the individual data.

00:18:32 And then based on that sort of connect your data

00:18:35 to whatever the proper group is

00:18:37 within the whatever the scientific paper is

00:18:40 to make the suggestion of how like how that work

00:18:44 applies to your life.

00:18:47 And then that ultimately maps to like a recommendation

00:18:49 of what you should do with your life.

00:18:51 Like it all like this giant system

00:18:54 that ultimately recommends

00:18:55 you should drink more coffee or less.

00:18:58 Right, and we’ll have the genome in there as well.

00:19:00 You can upload that.

00:19:01 Yeah, it’s awesome.

00:19:02 So these programs will know us way better

00:19:04 than we do and our doctors as well.

00:19:07 The idea of going to a doctor once a year

00:19:08 for an annual checkup and having males get a finger

00:19:11 up their butt and you cough, that to me is a joke.

00:19:16 That’s medieval medicine.

00:19:18 And that’s very soon going to be seen as medieval.

00:19:21 Yeah, to me as a computer science person,

00:19:25 it’s always upsetting to go to the doctor

00:19:28 and just look at him and like realize

00:19:31 you know nothing about me.

00:19:33 Like you’re making your like opinions based on like,

00:19:38 it is very valuable, years of intuition building

00:19:42 about basic symptoms, but you’re just like it is medieval.

00:19:45 They’re very good at it.

00:19:47 In fact, doctors in medieval times were probably damn good

00:19:51 at working with very little.

00:19:53 But the thing is, I’d rather prefer a doctor

00:19:58 that doesn’t really know what they’re doing,

00:20:00 but has a huge amount of data to work with.

00:20:03 Well, you’re right.

00:20:03 And many of my good friends are doctors.

00:20:05 I work at Harvard.

00:20:06 So I’m not against the profession at all.

00:20:09 But I think that they need just as much help

00:20:11 as anyone else does.

00:20:13 We wouldn’t drive a car without a dashboard.

00:20:15 We wouldn’t think of it.

00:20:16 So why would doctors do the same?

00:20:18 If we could, could we step back to the big,

00:20:21 profound, philosophical, both tragic

00:20:23 and beautiful question about age?

00:20:26 How and why do we age?

00:20:28 Is it from an engineering perspective?

00:20:31 You said you like the biological machine.

00:20:33 Is that a feature or a bug of the biological machine?

00:20:37 It is both a bug and a feature.

00:20:40 Evolutionary speaking, we only live as long as we need to

00:20:44 to replace ourselves efficiently.

00:20:47 If you’re a mouse, you’re only gonna live two

00:20:49 and a half years, three years.

00:20:50 You’re probably gonna die of starvation,

00:20:51 predation, freezing in the winter.

00:20:54 So they divert most of their resources

00:20:57 to reproducing rapidly,

00:20:59 but they don’t put a lot of energy

00:21:00 into preserving their soma, which is their body.

00:21:04 Conversely, a baleen type of whale,

00:21:06 a bowhead whale in particular will live hundreds of years

00:21:09 because they’re at the top of the food chain

00:21:11 and they can live as long as they want.

00:21:12 So they breed slowly and build a body that lasts.

00:21:15 We’re somewhere in between because we’ve, you know,

00:21:17 we’ve really only just come out of the savannas

00:21:19 where we could be picked off by a cat.

00:21:22 We were pretty wimpy going back 6 million years ago.

00:21:25 So we actually need to evolve quicker than evolution will.

00:21:30 And that’s why we can use our oversized brains

00:21:33 and intuition to give us what evolution

00:21:36 not only didn’t give us, but took away from us.

00:21:38 Now we’re pathetic, look at our bodies.

00:21:40 These arms, if any of us, even the strongest person

00:21:42 in the world went in a cage with a chimpanzee,

00:21:45 the chimp could knock that person’s head off, no question.

00:21:47 So we’re pathetic.

00:21:48 So we need to engineer ourselves to be healthier

00:21:50 and longer lived.

00:21:51 So getting to aging, we can do better, right?

00:21:55 Whales do way better.

00:21:57 We’re trying to learn how whales do that.

00:21:59 And if you ask really anybody in the field now, professor,

00:22:03 they’ll say there are eight or nine hallmarks of aging,

00:22:07 which are really, it’s a word for causes of aging.

00:22:11 So that you probably have heard of some of these,

00:22:13 your listeners will have loss of telomeres,

00:22:16 the ends of the chromosomes, like the little ends

00:22:19 of shoelaces, that kind of thing.

00:22:21 They get too short, cells stop dividing, become senescent.

00:22:24 They become, they put out what are called mitogens

00:22:28 that cause cancer and inflammatory molecules.

00:22:31 So that’s another aspect of aging, cellular senescence.

00:22:34 Another one is loss of the energetic.

00:22:35 So mitochondria, the battery packs wind down.

00:22:39 There’s a whole bunch, stem cells, proteostasis.

00:22:43 Well, these are our Achilles heels that I’m talking about.

00:22:45 They’re a common amongst all life forms, really.

00:22:48 But if you want me to jump to the chases to where,

00:22:51 what is the upstream defining factor?

00:22:54 If we boil it down, what do we get?

00:22:57 So most biologists would say, you can’t boil it down.

00:22:59 It’s too complex.

00:23:01 I would say you can boil it down to an equation,

00:23:03 which is the preservation of information

00:23:05 and loss due to entropy, i.e. noise.

00:23:09 And that is the basis of my research.

00:23:12 It originally came out of discoveries in yeast cells,

00:23:14 where I went to MIT in the 1990s.

00:23:17 You studied bread.

00:23:18 I kind of did.

00:23:20 I studied the makers of bread,

00:23:22 a little yeast called Saccharomyces cerevisiae,

00:23:25 which at the time was one of the hottest, excuse the pun,

00:23:29 organisms to work on.

00:23:30 But we figured out in the lab why yeast cells get old

00:23:35 and found genes that control that process

00:23:37 and made them live longer,

00:23:39 which was an amazing four years of my life.

00:23:41 One of those genes had a name with an acronym SIR2.

00:23:48 Now the two is irrelevant.

00:23:49 The SIR is important.

00:23:51 And the most important letter out of all of those three

00:23:53 is I, which stands for information.

00:23:56 Silent information regulator number two,

00:23:59 when you put more copies of that gene in,

00:24:01 just put in one more copy,

00:24:02 the yeast cells lived 30% longer

00:24:04 and suppressed the cause of aging,

00:24:06 which was the dysregulation of information in the cell.

00:24:09 And then, so fast forward to now,

00:24:11 I’ve been looking in humans and mice,

00:24:14 because they live shorter and cheaper to study,

00:24:17 where the loss of information in our bodies

00:24:20 is a root cause of aging.

00:24:22 And I think it is.

00:24:24 Your boldness in doing biology in this way is fascinating

00:24:29 because that also leads to a kind of,

00:24:31 it’s almost like allows for a theory of aging,

00:24:40 like you could boil it down to a single equation

00:24:43 and it leads to a, perhaps a metric

00:24:45 that allows you to optimize aging,

00:24:48 sort of in the fight against entropy.

00:24:51 I had to figure out which mechanisms, like you said,

00:24:53 the silent information regulator,

00:24:55 which mechanisms allow you to preserve information

00:24:58 without injecting noise, without creating entropy,

00:25:03 without creating degradation of that information.

00:25:07 For some reason, converting biology,

00:25:11 which I thought was mostly impossible

00:25:13 into an engineering problem,

00:25:15 feels like it makes it amenable to optimization,

00:25:19 to solving problems, to creating technology that can,

00:25:23 whether that’s genetic engineering or AI,

00:25:26 it makes it possible to create the technology

00:25:30 that would improve the degradation of information and aging.

00:25:36 Is there more concrete ways you think

00:25:38 about the kind of information you want to preserve?

00:25:41 And also, is there good ideas about regulators

00:25:46 of that information, about ways to prevent the distortion,

00:25:52 the degradation of that information?

00:25:54 Right, so we have silent information regulator genes

00:25:56 in our bodies.

00:25:57 We have seven of them, SIRT1 through seven, they’re called.

00:26:00 And we found in mice, one way to slow down

00:26:03 the loss of information is to just give more of these,

00:26:06 to upregulate these genes.

00:26:08 So we made a mouse that has more of this SIRT1 gene,

00:26:12 turned it on, and that slowed down the aging of the brain

00:26:15 and preserved their information.

00:26:16 Now, what information am I talking about, you might ask?

00:26:19 Well, again, you can simplify biology.

00:26:22 There are two types of information in the cell primarily.

00:26:25 The one we all read about and know about

00:26:27 is the DNA, the genome.

00:26:29 And that’s base four information, ATCG,

00:26:32 the four chemicals that make up the various sequences

00:26:35 of the genome, billions of letters.

00:26:37 And that also degrades over time.

00:26:39 But what’s been fascinating is that we find

00:26:42 that that information is pretty much intact

00:26:45 in old animals and people.

00:26:47 You can clone a dog.

00:26:48 One of my friends in LA just cloned his dog three times.

00:26:50 So this is doable, right?

00:26:52 It means that the genome can be intact.

00:26:53 But what’s the other type of information?

00:26:56 It’s the epigenome, the regulators

00:26:58 of the genetic information.

00:27:01 And physically, that’s really just how the DNA is wrapped up

00:27:04 or looped out for the cell to access it and read it.

00:27:08 So it’s similar to, and excuse this analogy,

00:27:11 but it’s a good one, a compact disc or a DVD.

00:27:15 Those pits in the foil are the digital information.

00:27:18 That’s the genome.

00:27:19 And the epigenome is the reader of that information.

00:27:22 And in a different cell, you’d read different music,

00:27:25 different songs, different symphonies.

00:27:28 And that’s what gets laid down when we’re in the womb.

00:27:31 And that makes a skin cell forever a skin cell

00:27:34 and not a brain cell tomorrow.

00:27:36 Thank God, otherwise our brains wouldn’t work very well.

00:27:38 But over time, what we see is that the brain cells

00:27:41 start to look more like skin cells.

00:27:42 And the kidney cells start to look more like liver cells.

00:27:45 And what we call X differentiate.

00:27:48 This is a term that we use in my lab,

00:27:49 but isn’t yet widely used.

00:27:52 But we needed a term to explain this.

00:27:53 And that process of X differentiation,

00:27:55 the loss of the reader of the CD or the DVD,

00:28:01 we liken that to scratches on the DVD

00:28:06 so that the reader cannot fully access the information.

00:28:09 Now we can slow down the scratches, as I mentioned.

00:28:11 We can turn on these genes.

00:28:13 We can even put in molecules into the cell

00:28:15 or even eat them and turn on those pathways,

00:28:18 which my father and I have been trying to do

00:28:21 for about a decade to slow things down.

00:28:24 But the question that I’ve had is,

00:28:27 is there a repository of information still in the body?

00:28:30 Because anyone who knows anything

00:28:32 about the loss of information

00:28:33 or even has tried to copy a cassette tape

00:28:35 or photocopy or Xerox anything knows that over time,

00:28:38 you lose that information irreparably.

00:28:41 So I’ve been looking for a backup copy,

00:28:43 inspired largely by Claude Shannon’s work

00:28:46 at MIT as well in the 1940s.

00:28:48 His mathematical theory of communication is just brilliant.

00:28:53 And so I’ve been looking for what he called the observer,

00:28:55 which is the backup copy.

00:28:57 We today might call that the TCPIP protocol of the internet

00:29:01 that stores information in case it doesn’t make it

00:29:04 to your computer, it will fill in the gaps.

00:29:06 And we’ve been spending about the last five years

00:29:09 to try and find if there really is a backup copy in the body

00:29:12 to reset the epigenome and polish those scratches away.

00:29:15 That’s incredible.

00:29:16 So finding the backup, so whenever there are too many

00:29:19 scratches pile up, you can just write a new version.

00:29:24 Like write, not a new version,

00:29:26 but go to the backup and restore it.

00:29:29 Right, that’s really all we’re talking about.

00:29:31 It’s not that hard once you know the trick.

00:29:34 And for people that actually remember like DVDs

00:29:38 and scratches on them, how frustrating it is.

00:29:41 That’s a brilliant metaphor for aging.

00:29:44 And then the reader is the thing that skips

00:29:51 and then it could destroy your experience,

00:29:53 the richness of the experience that is listening

00:29:55 to your favorite song.

00:29:57 Right, but in biology, it’s even worse

00:29:59 because you’ll lose your memory, your kidneys will fail,

00:30:01 you’ll get diabetes, your heart will fail.

00:30:03 And we call that aging and age related diseases.

00:30:06 So most people forget that diseases that we get

00:30:10 when we get old are 80 to 90% caused by aging.

00:30:13 And we’ve been trying to fix things with band aids

00:30:15 after they occur without even generally talking

00:30:19 about the root cause of the problem.

00:30:21 Is there the scratches, do those come from,

00:30:28 are those programmed or are they failures?

00:30:31 Meaning is it, so if it’s by design,

00:30:36 then there’s like a encoded timeline schedule

00:30:40 that the body’s just on purpose,

00:30:43 degrading the whole thing.

00:30:44 And then there’s the just the wear and tear

00:30:47 of like the scratches on a disc that happen through time.

00:30:50 Which one is it that’s the source of aging?

00:30:54 It’s more akin to wear and tear, there isn’t a program.

00:30:56 Getting back to evolution, there’s no selection for aging.

00:31:00 We’re not designed to age, we just live as long as we need

00:31:03 to and then we’re at the whim of entropy, basically.

00:31:06 Second law of thermodynamics, stuff falls apart.

00:31:09 We live a bit longer than age 40,

00:31:11 only because there are robust, resilient systems,

00:31:13 but eventually they fail as well.

00:31:15 Current limit to the human lifespan

00:31:16 where they completely fail is 122.

00:31:21 But I don’t like to think of it as wear and tear

00:31:23 because there’s two aspects to it.

00:31:25 There’s a system that’s built to keep us alive

00:31:28 when we’re young, but actually goes,

00:31:30 comes back to bite us as we get older.

00:31:33 And we call this issue antagonistic pleiotropy.

00:31:37 What’s good for you when you’re young

00:31:39 can cause problems when you’re older.

00:31:42 So we’ve been looking, what is the main causes of the noise?

00:31:46 And we’ve found two of them definitively.

00:31:49 The first one is broken chromosomes.

00:31:52 When a chromosome breaks, the cell has to panic

00:31:55 because that’s either gonna cause a cancer or kill the cell.

00:31:58 There’s only two outcomes, it’s pretty much a problem.

00:32:01 And so what the cell does is it reorganizes the epigenome

00:32:05 in a massive way.

00:32:06 What that leads to is, think of it as a tennis match

00:32:09 or a ping pong game.

00:32:11 The proteins are the balls

00:32:13 and they now leave where they should be,

00:32:14 which is regulating the genes that make the cell type,

00:32:18 whatever it is.

00:32:18 And they have a dual function,

00:32:20 they actually go to the break,

00:32:22 the chromosome will break and fix that.

00:32:24 And then they come back.

00:32:26 You might ask, well, why is it set up that way?

00:32:28 Well, it’s a beautiful system,

00:32:29 it coordinates gene expression,

00:32:30 the control systems with the repair.

00:32:32 You want them coordinated.

00:32:34 Problem is, as we get older, this ping pong game,

00:32:36 some of the balls get lost.

00:32:37 They don’t come back to where they originally started.

00:32:40 And that’s what we think is the main noise for aging.

00:32:45 And we’ve also, the other cause of aging that we found

00:32:47 is cell stress, we damage nerves and they age rapidly.

00:32:51 So that’s the other issue.

00:32:52 There’s probably others, smoking chemicals, for example,

00:32:56 we know accelerates biological age pretty dramatically.

00:33:00 But the question is, can you slow that down

00:33:02 or can you reset them to get those ping pong balls

00:33:04 to go back to where they originally started in the game?

00:33:07 And we think we’ve found a way to do that.

00:33:09 Can you give me hints?

00:33:11 Whose fault is it in the balls not coming back?

00:33:13 Is it the proteins themselves?

00:33:15 Like are they starting?

00:33:18 Again, I’ve been obsessed with the protein folding problem

00:33:20 from the AI perspective.

00:33:21 So is it the proteins or is it something else?

00:33:23 Well, we know who hits the balls and recruits them.

00:33:27 So that the break is recognized by the cell.

00:33:31 It’s recognized by proteins who send out a signal

00:33:35 through phosphorylation is typical way cells talk

00:33:38 to other proteins.

00:33:40 And that recruits those repair factors,

00:33:43 those ping pong balls to the break.

00:33:45 So the cells actively doing this to try and help itself,

00:33:49 but we don’t know who’s to blame for them not coming back.

00:33:53 That could just be a flaw in the quote unquote design.

00:33:58 I don’t think that there’s something saying,

00:34:00 well, 1% of you balls proteins never go back.

00:34:04 I just think it’s hard to reset a system

00:34:06 that’s constantly changing.

00:34:07 We have in our bodies close to a trillion DNA breaks

00:34:11 every day.

00:34:12 And imagine that over 80 years,

00:34:14 what damage that does to our epigenomic information.

00:34:17 Now we know that this is, well,

00:34:20 we never know anything in biology,

00:34:21 but we have strong evidence that this is true

00:34:23 because we can mess with animals.

00:34:27 We can create DNA breaks and tickle them

00:34:30 with a few breaks, maybe raise it by threefold

00:34:32 over background levels of normal breakage.

00:34:35 And if we’re right, those mice should get old.

00:34:39 And they do.

00:34:40 We can actually, we’ve created these breaks

00:34:42 in a way that’s titratable.

00:34:43 We can, it’s like a rheostat.

00:34:45 We can send it to 11.

00:34:47 I drove my Tesla here, I’m a big fan of a spinal tap too,

00:34:51 going to 11.

00:34:52 If we go to 11, we can make a mouse old

00:34:54 in a matter of months.

00:34:55 We prefer to go to a level of about four

00:34:58 and it gets old in 10 months.

00:35:00 But it’s definitely old.

00:35:01 It’s got all of the hallmarks of aging.

00:35:03 It’s got diseases.

00:35:05 It looks old.

00:35:06 Its skin is old.

00:35:06 It’s got gray hair.

00:35:08 But importantly, we can now measure age

00:35:10 by looking at the scratches.

00:35:11 We can look at the epigenome, we can measure it

00:35:13 and use machine learning to give us a number.

00:35:15 And those mice are 50% older than normal.

00:35:19 So you can replicate the aging process in a controlled way.

00:35:21 You can, I mean, in a way that, I mean,

00:35:24 you could accelerate it in a controlled way

00:35:28 and measure how much exactly it’s aging.

00:35:31 And that gives you step one of a two step process

00:35:35 to when you can then figure out,

00:35:36 how can we reverse this?

00:35:38 And now we’re reversing those mice.

00:35:40 Is there a good, I love what you said.

00:35:42 I mean, in biology, you really don’t know.

00:35:45 It’s such a beautiful mess.

00:35:48 Is there ideas how to do that?

00:35:51 Is that on the genetic engineering level?

00:35:55 Is it like, what can you mess with?

00:35:57 Is it going to the, trying to discover the backup copies

00:36:02 and restoring from them?

00:36:04 Like what’s, if it’s possible to convert it

00:36:06 to natural language words, what are the ideas here?

00:36:09 What is the observer and how do we contact it?

00:36:11 Exactly.

00:36:12 What’s the observer and how do you contact?

00:36:14 Or if there’s other ideas, how to reverse

00:36:17 the balls getting lost process.

00:36:20 Yeah, well, you can slow it down.

00:36:22 Slow it.

00:36:23 But we found a reset switch recently.

00:36:26 We just published this in the December 2020 issue of Nature.

00:36:33 And what we found is that there were three embryonic genes

00:36:36 that we could put into the adult animal

00:36:39 to reset the age of the tissues.

00:36:42 And it only takes four to eight weeks to work well.

00:36:44 And we can take a blind mouse

00:36:46 that’s lost its vision due to aging.

00:36:48 Neurons aren’t working well towards the brain.

00:36:50 Reset those neurons back to a younger age.

00:36:52 And now the mice can see again.

00:36:55 These three genes are famous actually

00:36:57 because they’re a set of four genes

00:36:59 discovered by Shinya Yamanaka,

00:37:01 who won the Nobel Prize in 2016

00:37:04 for discovering that those four genes

00:37:05 when turned on at high levels in adult cells

00:37:09 can generate stem cells.

00:37:11 And this is, I think, well known now

00:37:14 that we can create stem cells from adult tissue.

00:37:16 But what wasn’t known is can you partially take age back

00:37:19 without becoming a tumor

00:37:20 or generating a stem cell in the eye,

00:37:22 which would be a disaster?

00:37:24 And the answer is yes.

00:37:24 There is a system in the body

00:37:26 that can take the age of a cell back to a certain point,

00:37:29 but no further, safely, and reset the age.

00:37:33 And we’re now using that to reset the age of the brain

00:37:36 of those mice that we aged prematurely.

00:37:39 And they’re getting their ability to learn back.

00:37:42 This is really exciting, right?

00:37:44 Like what’s the downside of this?

00:37:46 Well, the downside is if you overdo it

00:37:49 and you don’t get it right, you might cause tumors.

00:37:53 But we do it very carefully.

00:37:54 And we also know that in the eye, it’s very safe.

00:37:57 We also injected these, we deliver them by viruses.

00:38:01 So we can control where and when they get turned on.

00:38:07 And in this paper, we’ve published

00:38:08 that if we put high levels in the mouse,

00:38:10 into their veins, throughout the body,

00:38:12 they don’t get cancer for over a year.

00:38:14 So I’m so optimistic that we’re going into human studies

00:38:18 in less than two years from now.

00:38:20 Is there a place where AI can help?

00:38:23 Sorry to inject one of the things

00:38:27 I’m very excited about and passionate about.

00:38:30 So Google DeepMind recently had a big breakthrough

00:38:35 with AlphaFold2, but also AlphaFold two years ago,

00:38:39 with achieving sort of a state of the art performance

00:38:44 on the protein folding problem, single protein folding.

00:38:47 But it also paints a hopeful picture

00:38:50 of what’s possible to do in terms of simulating

00:38:52 the folding of proteins,

00:38:54 but also simulating biological systems through AI.

00:38:58 Is there something to you, combined with this brilliant work

00:39:02 on the biology side that you’re hopeful about

00:39:05 where AI can be a tool to help?

00:39:08 Where isn’t it a tool?

00:39:09 I mean, if you’re not using AI right now in biology,

00:39:11 you’re getting less and less likely

00:39:13 to be left behind in biology, you’re getting left behind.

00:39:15 We use it all the time.

00:39:16 We’re using it to generate these biological clocks

00:39:19 to be able to read those scratches.

00:39:21 We’re using it to predict the folding of proteins

00:39:24 so we can target molecules and modulate their activity.

00:39:28 We’re using it to assemble genomes of different species.

00:39:31 What else?

00:39:32 We use it to predict the longevity of a mouse

00:39:36 based on how it reacts to certain things,

00:39:39 hearing, eyesight, generally frailty.

00:39:41 We just put out a paper last year on that.

00:39:45 The other thing we can use it for,

00:39:46 which is a little off the track here,

00:39:49 but we use it for predicting

00:39:51 which microorganisms are in your body,

00:39:53 actually not predicting, telling you.

00:39:55 So our daughter, Natalie, was infected with Lyme disease

00:39:59 a few years ago, almost went blind from it.

00:40:02 And the test took four days.

00:40:03 And I thought, just give me the DNA from her spinal fluid.

00:40:06 I’ll go tell you what’s in it.

00:40:07 If it’s Lyme disease or not, they refused.

00:40:10 And so at that point I said, this has to be done better.

00:40:12 So I’ve started a company that now can take a sample

00:40:15 of any part of your body.

00:40:17 It’s typically done now with liver transplant patients

00:40:21 to detect viruses that come out of their organs.

00:40:24 But that’s another area that AI is extremely important for.

00:40:29 I think if you’re not, in five years,

00:40:31 if you’re not using deep learning, you’ve got a problem.

00:40:35 Because the amount of data that we generate now

00:40:36 as biologists is just terabytes.

00:40:39 It can be terabytes per week.

00:40:40 It’ll eventually be terabytes per day.

00:40:42 And then we just go from there.

00:40:43 And I actually have trouble recruiting enough

00:40:46 bioinformaticians.

00:40:49 A lot of our work is now just number crunching.

00:40:52 A part of that is collecting the data,

00:40:55 which is kind of something we’ve talked a little bit about.

00:40:57 But is there something you can say about

00:41:00 how we can collect more and more data,

00:41:04 not just on the one person level,

00:41:07 like for you to understand your various markers,

00:41:13 but to create huge datasets

00:41:16 to understand how we can detect certain pathogens,

00:41:20 detect certain properties, characteristics

00:41:22 of whether it’s aging or all the other ways

00:41:25 that the human body can fail.

00:41:27 It seems like with biology,

00:41:29 there’s a kind of privacy concerns that,

00:41:33 well, actually not privacy concerns,

00:41:34 it’s almost like regulation that kind of prevents

00:41:38 hospitals from sharing data.

00:41:42 I’m not sure exactly how to say it,

00:41:44 but it seems like when you look at autonomous vehicles,

00:41:48 people are much more willing to share data.

00:41:50 When you look at human biology system,

00:41:52 people are much less willing to share data.

00:41:54 Is there a hopeful path forward

00:41:56 where we can share more and more data at a large scale

00:42:00 that ultimately ends up helping us understand

00:42:03 the human body and then treat problems with the human body?

00:42:06 So we are right in the middle,

00:42:08 we’re living through what’s gonna be seen

00:42:10 as one of the biggest revolutions in human health,

00:42:12 through the gathering of data about our bodies.

00:42:16 And 20 years ago, people didn’t wanna go on social media,

00:42:19 they’re worried about it, now you have to,

00:42:21 if you’re a kid, that’s for sure.

00:42:23 Same with medical records,

00:42:25 these are becoming all digitized and expanded.

00:42:29 Ultimately, we’re going to, even if we don’t want to,

00:42:32 have to be monitored.

00:42:34 There’s gonna be a court case that,

00:42:36 I bet two, three years from now, someone’s gonna say,

00:42:39 how come my father died from a heart attack?

00:42:42 You had these biosensors, 20 bucks, and you didn’t use it.

00:42:45 Lawsuit right there, and suddenly,

00:42:47 all hospitals have to give you one of these.

00:42:49 There’ll be a reversal, like to where,

00:42:52 it’s your fault if you don’t collect the data,

00:42:54 that’s brilliant, and that’s absolutely right.

00:42:58 I mean, that’s absolutely right.

00:43:00 That’s the frustration I feel on going to the doctor,

00:43:03 is like, it’s almost negligent to not collect the data,

00:43:10 because you’re making,

00:43:11 there’s something really wrong with me,

00:43:13 and you’re making decisions based on very few tests,

00:43:17 that’s almost negligent, when you have the opportunity

00:43:20 to collect a huge amount more data.

00:43:21 Well, let me tell you something.

00:43:23 Like, I’ve got this inside tracker data

00:43:26 for myself over a decade,

00:43:29 and you’d think my doctor would roll his eyes at this,

00:43:31 oh, he’s gone to a consumer company, blah, blah, blah.

00:43:34 I had my first checkup in a year with him

00:43:37 through video conference, and he was running blind.

00:43:42 He really didn’t know what was going on with me.

00:43:45 He asked the usual things.

00:43:46 How am I sleeping?

00:43:47 How am I eating?

00:43:48 These kind of usual things.

00:43:50 And I said, well, I’ve got new tests back

00:43:52 from inside tracker, and he said, great,

00:43:54 I’d love to see them.

00:43:55 So I share screen, and we look at the graphs,

00:43:58 look at the data, and he’s loving it,

00:44:00 because he cannot order these tests willy nilly.

00:44:04 So I said, well, let’s order a HbA1c blood glucose levels,

00:44:08 because I’m very interested in that.

00:44:10 That tracks with longevity.

00:44:11 And he said, well, I have no reason to order that.

00:44:13 Do you have a family history?

00:44:15 No.

00:44:17 Do you have any symptoms of diabetes?

00:44:18 No.

00:44:19 Well, I can’t order the test.

00:44:20 I almost wanted to reach through the computer

00:44:22 and strangle him, but instead, I pay a little bit

00:44:25 to get these tests done, and then he looks at them.

00:44:28 So that’s now the way consumer health is going,

00:44:30 is that you can get better data than your doctor can,

00:44:32 but they’d like you to do that.

00:44:34 Quick human question, maybe you can educate me.

00:44:39 I think doctors sometimes have a bit of an ego.

00:44:42 I understand that the doctors super experience

00:44:44 a lot of things, but this is a fundamental question

00:44:47 of human variability.

00:44:49 Like, I know a lot of specific details about like,

00:44:52 I mean, it depends, of course, what we’re talking about,

00:44:54 but I bring a lot of knowledge, and if I have data with me,

00:44:58 then I have like several orders of magnitude more knowledge.

00:45:02 And I think there’s an aspect to it where the doctor

00:45:05 has to put their expert hat, like take it off

00:45:11 and actually be a curious, open minded person

00:45:14 and study and look at that data.

00:45:16 Do you think it’s possible to sort of change the culture

00:45:19 of the medical system to where the doctors are almost,

00:45:22 as you said, are excited to see the data?

00:45:25 Or is that already happening?

00:45:26 It’s really happening.

00:45:27 Now, we’ve probably lost the last generation.

00:45:30 They’re no hopers, but so I teach at Harvard Medical School

00:45:34 and they’re excited about this.

00:45:35 They’re excited about aging,

00:45:37 which is a new aspect to medicine.

00:45:39 Oh, wow, we can do something about that.

00:45:41 And then, yeah, all this data, what do we do with it?

00:45:43 There’s still the traditional pathology and all that stuff,

00:45:45 which they need to know, but time will change their mindset.

00:45:52 I’m not worried about that.

00:45:54 And like we were discussing, this isn’t a question of if,

00:45:57 it’s just a matter of when.

00:45:58 And I have a front row seat on all of this.

00:46:02 I had breakfast with a CEO who is making this happen

00:46:07 just yesterday.

00:46:09 I can tell you for sure that most people have no idea

00:46:12 that this revolution is occurring

00:46:14 and is happening so quickly.

00:46:17 If you’re running a hospital and you can save $2,000

00:46:19 per cardiac patient, what are you going to do?

00:46:22 You have to use it.

00:46:23 Otherwise, the hospital down the road

00:46:25 is going to be beating you.

00:46:28 And there are large hospital aggregations,

00:46:30 so there’s Ascension and others,

00:46:32 that just have to go this way for budgetary reasons.

00:46:37 And right now, the US spends 17% of their GDP on healthcare.

00:46:43 Let’s say one of these buttons on my chest costs $20.

00:46:45 It’s rechargeable.

00:46:47 And it can predict people’s health

00:46:48 and save on antibiotics to prevent heart attacks.

00:46:52 How many billions, if not trillions of dollars,

00:46:54 will that save over the next decade?

00:46:58 Yeah, so when the public wakes up to this,

00:47:00 they’ll almost demand it.

00:47:01 Like, this should be accepted everywhere.

00:47:04 This is obvious.

00:47:04 It’s going to save a lot of money.

00:47:05 It’s going to improve the quality of life.

00:47:07 Well, and the CFOs of hospital groups will have to.

00:47:11 And insurance companies are going to want to get in on this.

00:47:15 So now that gets to privacy, right?

00:47:17 Should an insurance company have access to your data?

00:47:20 I would say no.

00:47:21 But you could voluntarily show them some of it

00:47:24 if they give you a discount.

00:47:25 And that’s also being worked on right now.

00:47:28 I hope we do create kind of systems

00:47:30 where I can volunteer to share my data

00:47:33 and I can also take the data back,

00:47:35 meaning like delete the data, request deletion of data.

00:47:39 And then maybe policy creates rules

00:47:41 to where you can share data, you could delete the data.

00:47:45 And I think if I have the option to delete all my data

00:47:50 that a particular company has,

00:47:52 then I’ll share my data with everyone.

00:47:55 I feel like if, because that gives me the tools

00:48:01 to be a consumer, an intelligent consumer,

00:48:04 of awarding my data to a company that deserves it

00:48:08 and taking it back when the company is misbehaving.

00:48:11 And in that way, encourage,

00:48:13 as a consumer in the capitalist system,

00:48:15 encourage the companies that are doing great work

00:48:18 with that data.

00:48:20 Well, yeah, healthcare data security is number one.

00:48:24 On my mind, InsideTracker made sure that that was true.

00:48:27 But these buttons on your chest,

00:48:31 there’s very private stuff they can probably tell

00:48:33 if you’re having sex one night, right?

00:48:35 So this is not the kind of stuff you want leaked.

00:48:37 So I don’t know whether it’s blockchain or something.

00:48:39 Speak for yourself.

00:48:40 I want this public.

00:48:41 The live stream.

00:48:43 I guess it depends on how you go.

00:48:45 But there’s a lot of stuff you don’t want out there.

00:48:48 And this definitely has to be number one

00:48:51 because it’s one thing to have your credit card

00:48:54 information stolen, it’s another thing

00:48:55 your health records are permanently out there.

00:48:57 Yeah.

00:48:58 So there’s, on the biology side,

00:48:59 super exciting ways to slow aging.

00:49:03 But there’s also on the lifestyle side.

00:49:05 I recently did a 72 hour fast.

00:49:08 It’s just an opportunity to take a pause

00:49:09 and appreciate life.

00:49:12 Think about, there’s something about fasting

00:49:14 that encourages you to reflect deeper

00:49:19 than you otherwise might.

00:49:22 The time kind of slows.

00:49:24 And you also realize that you’re human

00:49:25 because your body needs food.

00:49:27 And you start to see your body’s almost as a machine

00:49:30 that takes food and produces thoughts.

00:49:33 And then ends briefly.

00:49:36 I mean, you start to, depending who you are,

00:49:39 if you’re like engineering minded,

00:49:41 you start to think of this whole thing

00:49:43 as a kind of, yeah, as a machine.

00:49:46 And then also feelings fill this machine.

00:49:50 Feelings of gratitude, of love,

00:49:52 but also the uglier things of jealousy

00:49:56 and greed and hate and all those kinds of things.

00:49:59 You start to think, okay, how do I manage this body

00:50:04 to create a rich experience?

00:50:06 All of that comes from fasting for me.

00:50:07 Anyway, but there’s also health benefits to fasting.

00:50:11 I intermittent fast a lot.

00:50:13 I eat just one meal a day most of the time.

00:50:16 Is there something you could say

00:50:18 about the benefits of fasting in your own life

00:50:20 and in general the anti aging process?

00:50:23 Well, you’re a philosopher too.

00:50:25 Sorry, I apologize.

00:50:26 No, I’m impressed.

00:50:28 True Renaissance man.

00:50:30 It’s a joy to be here.

00:50:31 So when it comes to fasting, this is,

00:50:34 being abstemious is one of the oldest ways

00:50:37 to improve health.

00:50:38 Probably they knew this 5,000 plus years ago.

00:50:41 So that’s not new.

00:50:43 But what we’re figuring out is what is optimal

00:50:45 and how does it work?

00:50:47 And one of the things we help contribute to,

00:50:49 which I can speak to with some authority

00:50:51 is that these longevity genes we work on,

00:50:54 we showed back in the early 2000s

00:50:56 are turned on by fasting.

00:50:58 And at least in yeast, we were the first to show

00:51:01 that how calorie restriction fasting works

00:51:03 to extend lifespan.

00:51:04 And that was the first for any species.

00:51:06 Something similar happens in our bodies.

00:51:08 When we’re hungry or put our bodies

00:51:10 under any other perceived adversity,

00:51:12 such as running, our bodies think,

00:51:14 wow, we’re getting chased by a saber tooth cat or something.

00:51:19 If we’re really hot or cold, these probably also work.

00:51:22 To put our bodies in this defensive state,

00:51:24 to activate these genes in the way that whales do

00:51:27 and mice don’t.

00:51:28 And so hunger is the best way to do that.

00:51:31 In fact, I don’t think you have to feel hungry.

00:51:33 You can get used to it.

00:51:35 But if there was one thing I would recommend

00:51:37 to anybody to slow down aging

00:51:39 would be to skip a meal or two a day.

00:51:42 Now it doesn’t mean you don’t have to live well.

00:51:44 You can go out.

00:51:45 I go to restaurants, I eat regular food.

00:51:47 I try to be as healthy as possible.

00:51:49 But I’ve gone from skipping breakfast most of my life

00:51:53 now just skipping lunch as well.

00:51:55 And I have my physique back that I had when I was 20.

00:51:59 I feel 20 mentally.

00:52:01 I’m much sharper.

00:52:02 I don’t feel tired anymore.

00:52:03 I sleep well.

00:52:04 So I’m a huge fan of the one meal a day thing.

00:52:07 Where I’m not good at is going beyond one day.

00:52:11 But if you do three days.

00:52:11 Have you ever fasted longer than 24 hours?

00:52:15 I tried doing two days.

00:52:17 I might have made it to the third and given up.

00:52:20 I just find that I’m not very,

00:52:22 I don’t have a lot of willpower.

00:52:23 I also hate exercise.

00:52:24 So I’m not sure how long I’m gonna live.

00:52:27 But I’ve managed to do one meal a day.

00:52:29 So if I can do that, seriously, anybody can do that.

00:52:33 To your listeners and viewers, I would say,

00:52:35 don’t try to do it all at once.

00:52:38 You can’t go from snacking and eating three meals a day

00:52:40 to what I do easily.

00:52:42 Work your way up to it, but also compensate with drinking.

00:52:45 If you like tea, if you like coffee, put some milk in it.

00:52:48 That’s fine.

00:52:49 You can fill your stomach up with liquids,

00:52:52 diet sodas, I get criticized for drinking,

00:52:54 but I’m gonna continue to have those.

00:52:56 But then I power through the day.

00:52:58 I definitely don’t feel tired.

00:52:59 I don’t have a lag anymore.

00:53:00 But also give it at least two weeks

00:53:02 because there’s a habit as well.

00:53:04 Having something in your mouth, chewing,

00:53:06 feeling that fullness, you can break that habit.

00:53:09 And within two, three weeks, you’ll have done it.

00:53:12 Absolutely.

00:53:12 So I’m not actually even that strict about it.

00:53:14 You said diet soda.

00:53:15 Yeah, people are very kind of weirdly strict

00:53:18 about fasting, the rules in fasting.

00:53:20 Like for example, I drank Element electrolytes

00:53:25 when I was fasting, and that has like five calories.

00:53:28 And so technically it’s not fasting.

00:53:31 Or people will say like, if you drink coffee,

00:53:33 there’s caffeine, and they’ll say

00:53:35 that’s technically not fasting

00:53:36 because there’s some kind of biological effects

00:53:38 of caffeine, but whatever.

00:53:40 Of course, there’s like biological benefits

00:53:42 that you can argue about,

00:53:43 but there’s also just experiential benefits.

00:53:45 Just calorie restriction broadly has a certain experience

00:53:49 to it that, like for me personally,

00:53:52 just as you said, has made me feel really good.

00:53:55 That said, especially, I’ve gained quite a bit of weight,

00:54:01 maybe even like 15 pounds, something like that,

00:54:03 since I moved to Austin, Texas.

00:54:05 And I still keep the same diet,

00:54:08 but I eat a lot of meat in that one,

00:54:12 just because it’s delicious,

00:54:14 because it’s also the amazing people I met in Texas.

00:54:19 It’s just there’s like a camaraderie,

00:54:21 a friendship, a love to the people

00:54:23 that like makes you really enjoy

00:54:25 the atmosphere of eating the brisket and the meat.

00:54:29 Is this Joe Rogan insisting?

00:54:31 Joe is, I mean, he’s very different.

00:54:34 Joe loves bread and pasta.

00:54:38 Like he knows that his body feels best

00:54:42 doing keto or carnivore.

00:54:44 So that’s what he usually tries to stick to,

00:54:47 but he also does not hold back,

00:54:50 and he’ll just eat pasta when he eats pasta,

00:54:52 and he sort of enjoys life in that way.

00:54:55 I can’t, I don’t know how to enjoy life in that way.

00:54:57 I also love pasta, but I’m just not going to enjoy it,

00:55:01 because I know my body ultimately

00:55:05 does not feel good with pasta.

00:55:06 So it’s a funny kind of dichotomies.

00:55:09 I would like to cheat, I guess,

00:55:13 by eating more meat than I, you know, like overeating

00:55:19 on the things that I know my body feels good on

00:55:22 as opposed to eating stuff I shouldn’t,

00:55:24 like cake and all those kinds of things.

00:55:26 I tend to find happiness in overeating the good stuff

00:55:32 versus eating the bad stuff.

00:55:35 And that’s the kind of balance.

00:55:37 Him, he’s like, fuck it.

00:55:41 Every once in a while, you gotta enjoy it.

00:55:43 And then also coupled with that for him

00:55:47 is just exercise, like then face his demons the next day

00:55:51 and just like burn a huge amount of calories,

00:55:53 which is, I mean, whatever’s up with that guy’s mind,

00:55:58 there’s an, there’s a ability to fully experience life,

00:56:03 which is represented by the pasta,

00:56:05 and the ability to just like fight the demons,

00:56:09 which is represented by all the crazy kettle balls

00:56:11 and running the hills and all this kind of stuff

00:56:13 that he does.

00:56:14 That takes a lot out of you doing

00:56:16 that kind of insane exercise.

00:56:17 And I think I’m more like you,

00:56:20 or at least towards your direction is like,

00:56:22 I really hate exercise.

00:56:24 So I do it, but I really hate it.

00:56:26 And so it’s a balance that you have to strike.

00:56:29 Is there something you could say about the diet side of that

00:56:33 for you personally, but in general,

00:56:36 in order to achieve calorie restriction,

00:56:39 like for me, eating, I know it may not sound healthy,

00:56:43 but eating carnivore, eating mostly meat

00:56:47 has been, has made me feel really good,

00:56:50 both mentally and physically.

00:56:52 Is there something you could say about the kinds of diets

00:56:56 that may improve longevity,

00:56:57 but also enable calorie restriction?

00:57:01 Well, sure.

00:57:02 I mean, the first thing that’s important to know

00:57:04 is that while many people are interested slash obsessed

00:57:08 with what they eat,

00:57:11 the data that’s come out of animal studies at least

00:57:13 is it’s far more important when you eat than what you eat.

00:57:17 And this was a fantastic study a few years ago

00:57:20 by my friend, Rafael de Cabo

00:57:22 at the National Institutes of Health in Bethesda.

00:57:24 And he had 10,000 mice on different diets,

00:57:26 hoping to find the perfect mix of carbs, protein, and fat.

00:57:30 And it turns out that the only ones that lived longer

00:57:33 are the ones that only ate once a day.

00:57:35 And so that, if we’re not mice,

00:57:37 but I think that we’re close enough to mice

00:57:40 that this tells us a lot.

00:57:42 But okay, but I still think the best bang

00:57:44 for the longevity buck is to do both well,

00:57:47 eat less often and eat the right things.

00:57:51 Now I’ll preface this to say, I’m not a nut about this.

00:57:54 I will eat occasional, very occasionally a dessert.

00:57:57 Usually I steal from others, which doesn’t count, right?

00:58:00 Exactly.

00:58:01 But you gotta live life, right?

00:58:02 What’s a long life if it’s not enjoyable anyway?

00:58:05 But what I also found, and this is,

00:58:08 I’ll get to your question in a second,

00:58:09 but my microbiome right now and stomach is at a point

00:58:12 where if I try to overeat on a steak,

00:58:15 which I did a couple of days ago,

00:58:16 I actually had a chicken, a fried chicken specifically,

00:58:22 for two days, I felt terrible.

00:58:23 I couldn’t sleep, it wouldn’t go down.

00:58:26 So I’m now at a point where even if I want to binge

00:58:28 on meat and fried foods, I just can’t, it just feels bad.

00:58:32 But what do I recommend?

00:58:34 Well, what the data says, which I try to follow,

00:58:37 is that plant based foods will be better

00:58:40 than meat based foods.

00:58:41 And I know that there are a lot of people who disagree.

00:58:43 But one of the facts is, well, there’s a few facts.

00:58:46 One is that people who live a long time

00:58:47 tend to eat those type of diets.

00:58:48 Mediterranean, Okinawa diet,

00:58:51 they’re eating mostly plants with a little bit of meat

00:58:53 and not a lot of red meat.

00:58:55 And the other fact is that in animals we know

00:58:58 that there’s a mechanism that’s called mTOR,

00:59:01 little m, capital TOR, that responds to certain amino acids

00:59:05 that are found in more abundance in meat.

00:59:07 And when it responds, it actually shortens lifespan.

00:59:10 And the converse, if you starve it

00:59:11 of those three amino acids, mostly in meat,

00:59:15 then it extends lifespan.

00:59:17 And there’s a drug called rapamycin,

00:59:19 which some people are experimenting with, that does that.

00:59:22 So you might be able to, I’m just saying this here

00:59:25 from all my colleagues, we don’t know the results here,

00:59:27 but you could potentially take a rapamycin like drug

00:59:30 and counteract the effects of meat in the long run.

00:59:34 Dono, we should try that actually,

00:59:35 we could do that in the lab.

00:59:37 But getting to the bottom of this,

00:59:39 what I think is going on is that

00:59:41 just like testosterone and growth hormone,

00:59:42 you will get temporary, maybe not temporary,

00:59:47 immediate health benefits.

00:59:48 You’ll feel great, you’ll get more muscle energy.

00:59:51 But the problem is I think it’s at the expense

00:59:54 of longterm health and longevity.

00:59:56 Well, this is actually something I worry about

01:00:00 in terms of longterm effects or the cost

01:00:05 in terms of longevity.

01:00:05 It’s very difficult to know how your choices

01:00:08 affect your longevity because the impact is down the line.

01:00:12 Like just because something makes me feel good now,

01:00:17 like eating only meat makes me feel good now,

01:00:20 I wonder what are the costs down the line.

01:00:22 Well, think about what I was saying about the trade offs

01:00:24 between growth and reproduction,

01:00:27 which is what a mouse does and a whale

01:00:29 that grows slowly, reproduces slowly, lives a long time.

01:00:33 It’s called the disposable soma theory.

01:00:35 Koch would just propose that in the 70s.

01:00:38 What meat probably does is put you in the mouse category,

01:00:42 super fertile, grow fast, heal fast.

01:00:44 And then if you wanna be a whale,

01:00:46 you should restrict meat and do things

01:00:49 that promote the preservation of your body.

01:00:53 Is it difficult to eat a plant based diet

01:00:57 that you perform well under?

01:01:00 So mentally and physically, just almost,

01:01:02 I’m asking almost like an anecdotal question

01:01:06 or unless you know the science.

01:01:09 Well, the science is still being worked out,

01:01:12 but from the synthesis of everything that I’ve read,

01:01:15 I try to eat a diet that’s definitely full of leafy greens,

01:01:21 particularly spinach is great

01:01:22 because it’s got the iron that we need, plenty of vitamins.

01:01:25 I also try to avoid too much fruit and berries,

01:01:32 particularly fruit juice,

01:01:34 definitely avoid that sugar high.

01:01:35 Spiking your sugar is not healthy in the long run.

01:01:39 The other thing that’s interesting

01:01:40 is we discovered what we called xenohormetic molecules.

01:01:45 Let me unpack that because it’s a terrible name

01:01:47 and I take full responsibility

01:01:49 with my friend, Conrad Howards.

01:01:51 The Xeno means cross species

01:01:53 and hormesis is the term that what doesn’t kill you

01:01:57 makes you live longer and be healthier.

01:02:01 And so we’re getting cross species health improvements

01:02:04 by molecules that plants make.

01:02:06 And plants make these molecules

01:02:08 when they’re also under adversity or perceived adversity.

01:02:11 For instance, I understand

01:02:14 if you want really healthy, good oranges,

01:02:16 you can drive nails into the bark of the tree

01:02:19 before you harvest.

01:02:20 Same with wine, you typically want them to be dry

01:02:23 before you harvest or covered in fungus.

01:02:25 And that’s because these plants make these colorful

01:02:28 and xenohormetic molecules

01:02:30 that make themselves stress resistant,

01:02:33 turn on their sirtuin defenses, the serogenes remember.

01:02:37 And when we eat them, we get those same benefits.

01:02:40 That’s the idea and we’ve evolved to do so.

01:02:42 This isn’t a coincidence.

01:02:43 It’s my theory, our theory that we want to know

01:02:47 when our food supply is under adversity

01:02:49 because we need to get ready for a famine.

01:02:51 And so we hunker down and preserve our body

01:02:54 and by eating these colored foods,

01:02:55 so practically speaking, if it’s full of color

01:02:58 or if there’s been some chewing by a caterpillar,

01:03:01 organic, grown locally in local farms,

01:03:04 I’ll eat that versus a watery, insipid, light colored lettuce

01:03:11 that’s been grown in California.

01:03:12 So you want vegetables that have suffered.

01:03:14 You want the David Goggins as a vegetables.

01:03:16 That’s the xenohormetic molecules.

01:03:19 I love that term.

01:03:20 I’m gonna take that one with me, thank you.

01:03:23 Yeah.

01:03:24 Oh, I follow him on Instagram, he’s always screaming.

01:03:27 So you want that he’s basically

01:03:30 the xenohormetic version of a human.

01:03:36 I like it.

01:03:36 So these are the molecules that are representative

01:03:38 of the stress that a plant has been under.

01:03:43 Yeah, the best example of that is resveratrol,

01:03:46 which many people, including myself,

01:03:48 take as a supplement.

01:03:49 Grapes, grapevines produce that in abundance

01:03:52 when they’re dried out or they have too much light

01:03:55 or fungus and that we’ve shown activates

01:03:59 the Sertu enzyme in our bodies,

01:04:01 which remember is what extends lifespan in yeast

01:04:03 and slows down aging in the brain.

01:04:05 That’s beautiful.

01:04:06 Yeah, I tend to avoid fruit as well.

01:04:09 So green, veggies, anything that’s not very sweet.

01:04:12 So I would just say you’re relatively low,

01:04:15 like you try to avoid sugary things as well.

01:04:19 Yeah, I’m fairly militant about that.

01:04:21 I rarely would add sugar to anything.

01:04:23 Occasionally I would eat a slice of cheesecake,

01:04:27 but that would be maybe once or twice a year.

01:04:31 You have to give in occasionally.

01:04:32 But yeah, anything that’s sweet,

01:04:34 I would rather substitute something like Stevia

01:04:37 if I need a sugar hit.

01:04:40 What about exercise?

01:04:42 Your favorite topic.

01:04:45 Is there a part?

01:04:46 I don’t mind talking about it.

01:04:48 Okay, great.

01:04:49 Is there benefits to longevity from exercise?

01:04:53 Well, no doubt, that’s proven.

01:04:55 Just like fasting, it’s pretty clear that that works.

01:04:59 For example, there are studies of cyclists.

01:05:01 It was something like people that cycle

01:05:04 over 80 miles a week have a 40% reduction

01:05:07 in a variety of diseases, certainly heart disease.

01:05:10 So that’s not even a question,

01:05:11 but what’s interesting is that we’re learning

01:05:13 that you don’t need much to have a big benefit.

01:05:15 It’s an asymptotic curve.

01:05:17 And in fact, if you overdo it,

01:05:19 you probably have reduced benefits,

01:05:20 particularly if you start to wear out joints,

01:05:22 that kind of thing.

01:05:23 But just 10 minutes on a treadmill a few times a week,

01:05:26 lose your breath, get hypoxic, as it’s called,

01:05:28 seems to be very beneficial for longterm health.

01:05:32 And that’s the kind of exercise that I like to do, aerobic.

01:05:36 Though I do enjoy lifting weights,

01:05:38 so that is what I call my exercise,

01:05:40 which has other benefits,

01:05:41 including maintaining hormone levels, male hormone levels.

01:05:46 But also really why I do it is I want to be able

01:05:49 to counteract the effects of sitting for most of the day.

01:05:53 And as you get older, you lose muscle mass.

01:05:55 It’s a percent or so a year.

01:05:57 And I don’t wanna be frail when I’m older

01:05:59 and fall over and break my hip,

01:06:00 which happens every 20 seconds in this country.

01:06:04 So maintaining that strength,

01:06:05 but also doing the cardio for the longevity,

01:06:07 for avoiding the heart disease.

01:06:10 Yeah, I definitely, just like with fasting,

01:06:13 have the philosophical benefit of running long

01:06:15 and running slow.

01:06:17 I enjoy it, because it kind of clears the mind

01:06:19 and allows you to think,

01:06:20 and actually listen to brown noise as I run.

01:06:22 It really helps remove myself from the world

01:06:26 and just like zoom in on particular thoughts.

01:06:28 What are these brown noise?

01:06:29 It’s like white noise, but deeper.

01:06:31 So like the white noise is like shh,

01:06:35 and then brown noise is more like,

01:06:37 shh, like ocean.

01:06:39 That sounds great.

01:06:40 I might try that.

01:06:41 Yeah, yeah, it’s more soothing probably.

01:06:44 I’m not sure.

01:06:45 There could be science to this.

01:06:46 I need to look this up.

01:06:47 I’ve been meaning to.

01:06:48 But when I started,

01:06:52 this is maybe like five years ago,

01:06:53 I started listening to brown noise when I work.

01:06:56 And the first time I listened to it,

01:06:58 something happened to my mind

01:07:00 where it just went like zoomed in

01:07:03 to like, in a way that it felt like really weird.

01:07:07 Like how precisely it was able to sort of

01:07:11 remove the distractions of the world

01:07:14 and really help my mind.

01:07:16 Obviously, like the mind is trying to focus

01:07:19 and then it just enabled that process

01:07:21 of trying to focus on a particular problem.

01:07:24 I don’t know if this is generalizable to others.

01:07:26 People should definitely try it

01:07:27 if you’re listening to this.

01:07:28 Maybe it’s just my own mind,

01:07:30 but it’s funny, like it made me,

01:07:34 brown noise made me realize

01:07:35 that there’s probably hacks out there

01:07:38 that work for me

01:07:40 that I should be constantly looking for.

01:07:41 It’s almost like an encouraging

01:07:44 and motivating event

01:07:48 that maybe there’s other stuff out there.

01:07:49 Maybe there’s other brown noise like things out there

01:07:52 that truly like almost immediately make me feel better.

01:07:56 I don’t know if it’s generalizable to others,

01:07:57 but it does seem that it’s the case

01:08:00 that there’s probably for many others,

01:08:03 things like that that could be discovered.

01:08:05 And so it’s always disappointing

01:08:07 when I find things in life

01:08:10 that I wish I would have found earlier.

01:08:12 I got LASIK eye surgery a few years ago

01:08:17 and the first thought I had like the next day

01:08:19 when I woke up is like,

01:08:21 damn it, why didn’t I do this way earlier?

01:08:24 There’s all this stuff of that nature

01:08:27 that are yet to be discovered.

01:08:29 So it pays to explore.

01:08:31 You have a different mind, you have quite a beautiful mind.

01:08:34 So I suspect brown noise helps you focus

01:08:37 and cause you’re probably all over the place

01:08:39 if you don’t control it.

01:08:40 Yeah, exactly.

01:08:40 It means something about it.

01:08:42 It’s a programmer thing.

01:08:43 I don’t, programming is a really difficult mental journey

01:08:50 cause you have to keep a lot of things in mind.

01:08:52 You have to, so you’re constantly designing things

01:08:56 then you have to be extremely precise

01:08:58 by making those things concrete in code.

01:09:01 You also have to look stuff up on the internet

01:09:06 to sort of feed like information

01:09:08 and looking up stuff on the internet,

01:09:10 internet is full of like distracting things.

01:09:12 So you have to be really focused

01:09:13 in the way you look stuff up in pulling that information in.

01:09:16 So it requires a certain discipline and a certain focus

01:09:20 that I’ve been very much exploring how to do.

01:09:23 Like I do it really well in the morning,

01:09:26 coffee is involved, all those kinds of things.

01:09:28 You’re trying to optimize, keeping very positive inspired,

01:09:32 no social media, all those kinds of things

01:09:34 and trying to optimize for.

01:09:36 And everybody has their own kind of little journey

01:09:38 that they try to understand.

01:09:40 You get this from like writers

01:09:41 when you read about the habits of writers,

01:09:45 like the habits they do in the morning,

01:09:47 they usually write like two, three, four hours a day

01:09:49 and that’s it.

01:09:50 It’s like they optimize that ritual.

01:09:53 And then there’s always Hunter S. Thompson.

01:09:55 So sometimes it pays off to be wild.

01:10:01 What about sleep?

01:10:04 How important is sleep for longevity?

01:10:06 I would guess based on the evidence

01:10:10 that it’s really important

01:10:12 and because we don’t know for sure.

01:10:15 But what we know from animal studies is the following.

01:10:17 If you restrict sleep from a rat for just two weeks,

01:10:20 it’ll develop type two diabetes.

01:10:22 It’s that important.

01:10:23 So that’s the main thing.

01:10:25 What we also know is at the molecular level

01:10:28 that if you disrupt your sleep wake cycle,

01:10:33 so we actually have proteins that go up and down

01:10:35 that control our sleep wake.

01:10:36 All of us, most of our cells do that.

01:10:39 If you disrupt that, you’ll get premature aging.

01:10:42 And guess what?

01:10:43 The opposite is true.

01:10:44 That as you get older, that cycle,

01:10:46 the amplitude becomes diminished.

01:10:49 And this is why it’s harder to get to sleep

01:10:51 as you get older

01:10:52 and you’ve got all sorts of problems.

01:10:54 And I think what’s going on is this positive feedback loop,

01:10:56 which is a disaster in your old age,

01:10:59 which is you’re aging,

01:11:02 you can’t at this moment totally prevent that.

01:11:05 And then it’s disrupting your sleep

01:11:06 and you get not enough sleep

01:11:08 and then that’s gonna accelerate your aging process.

01:11:10 And so it’s known that the people who are shift workers

01:11:13 are most susceptible to certain age related diseases.

01:11:17 So your bottom line, you definitely wanna work on that.

01:11:19 It’s one of the reasons I have this ring on my finger,

01:11:21 which helps me optimize my sleep

01:11:23 and learn what I do the day before,

01:11:25 if it was a bad idea and I’ll stop doing that,

01:11:28 like eating a fried chicken.

01:11:31 I see you’re still carrying the burdens of that decision.

01:11:34 But yeah, sleep is one of those things

01:11:37 that’s making me wonder about the variability

01:11:41 between humans a little bit

01:11:43 and how science is often focused on,

01:11:47 like it’s not often focused on high performers

01:11:51 in a particular way.

01:11:53 And it’s looking at the aggregate

01:11:55 versus the individual cases.

01:11:57 For example, like for me,

01:11:59 I don’t know what the exact hours are,

01:12:00 but like power naps are incredible.

01:12:06 I tend to look at the metric of stress and happiness and joy

01:12:11 and try to optimize those.

01:12:13 So decreasing stress, increasing happiness

01:12:16 and using sleep as just one of the tools to do that.

01:12:20 Because like hitting the five, six, seven, eight,

01:12:23 nine hour mark or whatever the correct mark is,

01:12:27 I find that to be stress inducing for me

01:12:29 versus stress relieving.

01:12:32 Like thinking about that,

01:12:34 I feel best if I sleep sometimes for eight hours,

01:12:37 sometimes for four hours and then power nap.

01:12:39 And as long as I have a stupid private,

01:12:42 usually smile on my face,

01:12:44 that’s when I’m doing good,

01:12:46 as opposed to getting a perfect amount of sleep

01:12:49 according to whatever the latest blog post is.

01:12:53 And I also pull all nighters still.

01:12:56 I also think there’s something about the body,

01:12:59 like as long as you do it regularly,

01:13:02 it’s not as stress inducing.

01:13:04 Like you know what it is.

01:13:06 The reason I pull all nighters isn’t for like,

01:13:08 I’m playing Diablo three or something,

01:13:11 is because I’m doing something I’m truly passionate about.

01:13:13 Well, like I’m also love video games,

01:13:15 but I’m doing something I’m truly passionate about.

01:13:18 And it’s almost like there’s the Jocko Willing feeling

01:13:21 of when I’m up at 7 a.m. and I haven’t slept all night

01:13:25 and still I’m working on it.

01:13:27 There’s a kind of a celebration of the human spirit

01:13:29 that I really enjoy it.

01:13:31 Like, and that’s happiness.

01:13:33 And to sort of then,

01:13:35 and I usually don’t tell that kind of stuff to people

01:13:37 because their first statement will be like,

01:13:40 you should get more sleep.

01:13:42 It’s like, no, I’m doing stuff I love.

01:13:46 You should get more love in your life, bro.

01:13:48 That’s right.

01:13:50 So, but that said, in aggregate,

01:13:52 when you look at the full span of life,

01:13:55 is probably you should be getting

01:13:57 a consistent amount of sleep.

01:14:00 And it seems like it’s in that seven, eight hour range.

01:14:04 Yeah, but it’s similar to food.

01:14:06 It’s the quality, not the quantity, right?

01:14:09 And when you get it.

01:14:10 So I look at my data pretty often.

01:14:14 And what makes a difference to me is not the amount of hours,

01:14:17 but the quality, the depth and the deep sleep

01:14:20 is what will do it.

01:14:21 So if I have a lot of alcohol before going to sleep

01:14:24 and I can see my heart rate being different,

01:14:26 but what really kills me is that I don’t get a lot

01:14:28 of that deep sleep and I wake up barely remembering stuff.

01:14:32 So that, like you say, if you’re happy and contented

01:14:34 and you don’t have these cortisol chemicals

01:14:37 going through your body,

01:14:38 you will more naturally get into that deep state.

01:14:40 And even if you just get four hours,

01:14:42 way better than eight hours of none of that.

01:14:45 Yeah, yeah, that’s beautiful.

01:14:46 And some of that could be genetic.

01:14:48 For me, I just, I fall asleep like this.

01:14:51 If you want me to fall asleep right now, I can do it.

01:14:54 It’s no, I have no problem with it.

01:14:57 Combined with coffee, I just had two energy drinks.

01:14:59 I can probably sleep.

01:15:01 So that, I don’t know if that’s genetics

01:15:03 or it’s kind of, I don’t know what it is.

01:15:07 Or maybe that I don’t have kids and I’m single.

01:15:09 So I don’t have, I’m almost listening

01:15:11 to some kind of biological signal versus societal signal

01:15:15 on when I’m supposed to go to sleep.

01:15:17 So I just go to sleep whenever I feel like going to sleep.

01:15:20 Well, that’s because you’re a self employed.

01:15:22 Self employed.

01:15:23 Most people don’t have that luxury,

01:15:24 but we’re lucky, the two of us,

01:15:26 that we can make our own hours.

01:15:27 Yeah.

01:15:28 But yeah, it’s super important.

01:15:29 And those people who have shift work,

01:15:32 I mean, they really need to change the way that works

01:15:35 because they’re literally killing those people.

01:15:38 Is there something you could say about the,

01:15:41 the mind and stress in terms of effect on longevity?

01:15:48 Sort of, I don’t know if you think about it this way,

01:15:52 but when you talk about the biological machine,

01:15:55 it’s always these mechanisms that don’t,

01:15:57 are not necessarily directly connected to the brain

01:16:00 or the operation of the brain.

01:16:02 Like what’s the role about stress and happiness

01:16:06 and yeah, the sort of higher cognitive things

01:16:10 going on in the brain on longevity.

01:16:14 Right.

01:16:15 Well, that’s a great point that the brain

01:16:16 is the center for longevity.

01:16:18 Actually, we do know that.

01:16:21 For a start, when I’m stressed,

01:16:22 I can see mentally stressed,

01:16:24 then I can see it in my body.

01:16:27 Heart rate, hormones, it’s clear.

01:16:29 That’s no true surprise.

01:16:31 So you’ve got to work on your brain first and foremost.

01:16:33 If you are totally freaked out, agitated all the time,

01:16:38 you will live shorter.

01:16:40 I’m certain of it.

01:16:41 You know, I keep fish.

01:16:42 I’m a big aquarium guy.

01:16:46 And you can see the difference

01:16:47 between the fish that’s having a good time and dominant

01:16:50 and one that gets picked on.

01:16:52 It just looks like crap.

01:16:54 You don’t want to be that,

01:16:55 the little fish getting picked on if you can help it.

01:16:57 So I used to be extremely stressed as a kid.

01:17:00 I was a perfectionist, very shy,

01:17:02 always worried about being a failure.

01:17:05 If I didn’t get an A+, you know,

01:17:06 I was crying in my bedroom, that kind of sad existence.

01:17:10 I got into my twenties, then in my thirties,

01:17:12 and realized that’s not the way to live.

01:17:15 So I’ve worked very hard to get to this point

01:17:17 where I almost never get stressed, never.

01:17:20 There’s nothing that, I’ve never gotten angry in my lab.

01:17:23 I’ve got 20 kids.

01:17:24 Sometimes it’s like a,

01:17:25 most of the time it’s like a kindergarten.

01:17:28 I haven’t lost my temper.

01:17:29 I’m very calm, but that’s intentional.

01:17:32 And I don’t worry about stuff.

01:17:34 Millions of dollars, billions of dollars at stake sometimes.

01:17:39 Keep it cool.

01:17:39 It’s only life.

01:17:40 We’re all headed to the same place anyway.

01:17:42 Don’t worry about it.

01:17:44 But to answer your question, I think in a better way,

01:17:47 if you manipulate the brain of an animal,

01:17:50 I’ll give you an example.

01:17:51 If we turn on this CERT gene that I mentioned,

01:17:53 CERT1, we, a good friend of mine at WashU,

01:17:56 Sheena Mai did this.

01:17:58 They upregulated that gene

01:18:00 just in the neurons of the animal.

01:18:03 It lived longer.

01:18:04 So that’s sufficient to extend lifespan.

01:18:06 We also know that you can manipulate the part of the brain

01:18:09 called the hypothalamus,

01:18:10 which leeches a lot of chemicals into the body and proteins,

01:18:15 most of which we don’t know yet,

01:18:17 but just changing the inflammation of that little organ

01:18:20 or part of the brain is sufficient

01:18:22 to make animals live longer as well.

01:18:24 So get your brain in order first

01:18:26 before you tackle anything else, I would say.

01:18:29 So you kind of mentioned this,

01:18:31 with the inside tracker, there’s ability

01:18:34 to take blood measurement and then infer from that

01:18:39 a bunch of different things about your body

01:18:40 and how you can improve the longevity.

01:18:44 And you’ve also mentioned saliva

01:18:47 and more efficient ways to get data.

01:18:54 What does that involve?

01:18:55 What’s the future of data collection look like

01:18:57 for the human biological system?

01:18:59 Right, well, yeah, the issue with blood is

01:19:01 you need someone to take it.

01:19:03 I mean, or you prick your finger, which hurts.

01:19:06 So you’ve got to have something better.

01:19:07 So I think what the future looks like

01:19:08 is that you’ll spit onto a little piece of paper

01:19:12 and stick it in a machine and it’ll do that for you.

01:19:14 But we’re not there yet.

01:19:15 So the intermediate future that I’m building right now

01:19:20 is that you would take a swab of the inside of your mouth,

01:19:24 which is the easiest way to take cells out of your body

01:19:26 and just ship them off.

01:19:28 Okay, so it’s called a buckle swab.

01:19:30 I think we became very used to that.

01:19:32 Right now, because of COVID,

01:19:34 people don’t like going to the doctor as much.

01:19:36 They don’t like going out.

01:19:36 They just want to have home tests.

01:19:38 And so that I think is the next 10 years

01:19:40 where you’ll get a kit in the mail,

01:19:43 you’ll swab your cheeks, stick it back in an envelope,

01:19:45 send it off and a week later you have

01:19:48 either a doctor’s report or a health recommendation.

01:19:52 And what can you get off a cheek swab?

01:19:54 Well, you can get anything.

01:19:55 You can get hormones, stress levels,

01:19:58 stress hormones, blood glucose levels.

01:20:00 You can also tell your age reasonably accurately doing that,

01:20:04 actually quite accurately.

01:20:05 And those clocks can not just tell you

01:20:08 how you’re doing over time,

01:20:10 but can be used to give you recommendations

01:20:12 to slow that process down.

01:20:14 Cause some people sometimes are 10 years older biologically

01:20:16 than their actual chronological age.

01:20:19 I mean, why does it matter how many times

01:20:21 the earth’s gone around the sun seriously?

01:20:23 Who cares about birthdays?

01:20:24 It’s how long your body’s clock has been ticking

01:20:27 and how fast.

01:20:28 So I could take a cheek swab from you today, Lex,

01:20:31 take it back to my lab.

01:20:32 And we then by tomorrow tell you

01:20:35 how old you are biologically based on

01:20:37 what we call the epigenetic clock.

01:20:40 And you might be freaked out, you might be happy,

01:20:43 but either way we can advise you

01:20:45 on how to improve the trajectory.

01:20:47 Cause we know that smoking increases

01:20:49 the speed of that clock.

01:20:50 We also know that fasting and people who eat the right foods

01:20:54 have a slower clock.

01:20:55 Without that knowledge, you’re flying blind.

01:20:58 But I like the idea of a swab,

01:20:59 cause it’s just so easy.

01:21:01 A lot of us have done something like that for COVID tests.

01:21:03 It’s not a big deal.

01:21:04 I’ve been doing a nonstop rapid antigen test.

01:21:06 So let me say that particular one rapid antigen test,

01:21:11 they’ve been a source of frustration for me

01:21:12 because like everybody should be doing it.

01:21:14 It’s so easy.

01:21:16 We’ve also been working in my lab on democratizing

01:21:18 these tests to bring them down from a few hundred bucks

01:21:20 to a dollar.

01:21:22 So just to clarify,

01:21:22 you’re talking about not research,

01:21:24 you’re talking about like company stuff,

01:21:25 like actual consumer facing things?

01:21:28 Well, right.

01:21:29 The research on bringing the price down

01:21:30 has occurred in my lab at Harvard.

01:21:32 And then that intellectual property is being licensed

01:21:35 and has been licensed out to a company

01:21:37 that will be consumer facing.

01:21:40 So anybody for a small amount of money can do this.

01:21:43 Well, you got subscriber number one obsessed.

01:21:46 I think that’s a beautiful, beautiful idea.

01:21:48 So somebody who maybe I would have been more hesitant

01:21:51 about it until COVID,

01:21:54 but the home tests are super easy.

01:21:56 I almost wanted to share that data with the world,

01:21:59 like in some way, not the entirety of the data,

01:22:01 but like some visualization of like how I’m doing.

01:22:05 Like, it’s almost like when you share,

01:22:09 if you had like a long run or something like that,

01:22:11 I wish I could share because it inspires others.

01:22:14 And then you can have a conversation about like,

01:22:16 well, what are the hacks that you’ve tried

01:22:18 and have a conversation about like how to improve lifestyle

01:22:21 and those kinds of things that’s grounded in data.

01:22:23 That’s exactly, that’s what’s gonna happen.

01:22:25 Now, everything’s anonymous, of course.

01:22:27 We talked about security there,

01:22:29 but once it’s anonymized, you can then plot these numbers.

01:22:32 And I’ve plotted my epigenetic age

01:22:35 versus hundreds of other people

01:22:37 who have taken this test now.

01:22:39 And I can tell you where I fit relative to others

01:22:41 in terms of my biological age.

01:22:43 And I’m happy to share that with you

01:22:44 because it’s pretty low.

01:22:47 You can choose to share it, of course,

01:22:48 not everyone wants to share that.

01:22:50 But when you go to the doctor,

01:22:52 first of all, your doctor does treat you

01:22:54 as though you’re an average person

01:22:55 and none of us are average, there’s no such thing.

01:22:58 But second of all, we never know

01:23:00 how we’re doing relative to others

01:23:01 because we all, most of us, we don’t share our information.

01:23:05 So we might have this number and that number,

01:23:08 but do you know that your numbers are good for your age

01:23:10 or not?

01:23:11 You have no idea.

01:23:12 Even your doctor probably doesn’t even know.

01:23:14 So this graph that I’m talking about

01:23:16 is the beginning of a world where you can say,

01:23:18 how am I doing?

01:23:18 For the two of us, we’re white and we’re male

01:23:22 and we’re this age and we do this.

01:23:26 Are we good?

01:23:27 Are we doing the right things or the wrong things?

01:23:28 Do we need to fix certain things?

01:23:30 And this is what the future is.

01:23:32 It’s forget about just experimenting

01:23:35 and not knowing the result.

01:23:36 I mean, who doesn’t experiment and doesn’t look at the data?

01:23:38 No one, it makes no sense.

01:23:40 So we’re gonna enter a world

01:23:41 where we have a dashboard on our body,

01:23:43 the swabs, the blood tests, the biosensors

01:23:46 where our doctors can look at that,

01:23:48 but we can also look at it and they can recommend,

01:23:51 go to this restaurant down the road.

01:23:52 They’ve got this great meal.

01:23:54 It’s high in whatever you need today

01:23:56 because you’re lacking vitamin D and vitamin K2.

01:23:58 Go for it.

01:24:00 Ridiculous question or perhaps not.

01:24:03 If you look maybe 50 years from now

01:24:05 or 100 years from now, a person born then,

01:24:07 what do you think is a good goal

01:24:09 in terms of how long a person would live?

01:24:12 What is the maximum longevity that we can achieve

01:24:16 through the methods that we have today

01:24:19 or are developing some of the things

01:24:21 we’ve been talking about in terms of genetics,

01:24:25 in terms of biology?

01:24:27 Is there a number?

01:24:29 Right, well, so it changes all the time

01:24:31 because technology is changing so quickly.

01:24:33 I keep revising the number upward,

01:24:36 but I would say that if you do the right things

01:24:38 during your life and start at an early age,

01:24:40 let’s say 25, we don’t want malnutrition, starvation.

01:24:43 That’s not what I’m talking about.

01:24:45 But in your 20s, start eating the kind of diets

01:24:48 that I talked about, skipping meals.

01:24:51 In animals, that gives you an extra 20 to 30%.

01:24:55 We don’t know if that’s true for humans

01:24:57 and even 5% more would be a big deal for the planet.

01:25:03 I think that we should all aim to at least reach a century.

01:25:08 I’m a little bit behind.

01:25:09 I was born too early to benefit the most

01:25:12 from all of this discovery.

01:25:13 Those of you who are in your 20s,

01:25:16 you should definitely aim to reach a hundred.

01:25:18 I don’t see why not.

01:25:20 Consider this, this is really important.

01:25:23 The average lifespan of a human

01:25:25 that looks after themselves but doesn’t pay attention

01:25:29 is about 80, okay?

01:25:31 Japan, that’s the average age for a male, a bit higher.

01:25:35 If you do the right things in your life,

01:25:37 which is eat healthy food, don’t overeat,

01:25:41 don’t become obese, do a bit of exercise,

01:25:42 get good sleep and don’t stress,

01:25:44 that gives you on average 14 extra years.

01:25:47 That gets you to 94.

01:25:49 So getting to a hundred,

01:25:50 if you just focus on what I’m talking about,

01:25:52 it’s not a big deal.

01:25:53 So what’s the maximum?

01:25:54 Well, we know that one human made it to 122

01:25:57 and a number of them make it into their teens.

01:26:00 I think that’s also the next level

01:26:02 of where we can get to with the types of technologies

01:26:06 that I’m talking about.

01:26:07 Medicines, like I mentioned rapamycin,

01:26:09 there’s one called metformin, which is the diabetes drug,

01:26:12 which I take.

01:26:14 That in combination with these lifestyle changes

01:26:16 should get us beyond a hundred.

01:26:18 How long can we ultimately live?

01:26:19 Well, there’s no maximum limit to human lifespan.

01:26:22 Why can a whale live 300 years, but we cannot?

01:26:24 We’re basically the same structure.

01:26:26 We just need to learn from them.

01:26:27 So anyone who says, oh, you max out at X,

01:26:31 I think is full of it.

01:26:33 There’s nothing that I’ve seen that says

01:26:35 biological organisms have to die.

01:26:37 There are trees that live for thousands of years

01:26:39 and their biochemistry is pretty close to ours.

01:26:42 What do you think it means to live for a very long time?

01:26:44 Let’s say if it’s 200 years we’re talking about

01:26:47 or a thousand years.

01:26:50 There’s some sense, you could argue,

01:26:54 that there is immortal organisms already living on Earth,

01:26:58 like there’s bacteria.

01:26:59 So there’s certain living organisms

01:27:03 that in some fundamental way do not die

01:27:07 because they keep replicating their genetic,

01:27:10 they keep like cloning themselves.

01:27:12 Is it the same human if we can somehow persist

01:27:19 the human mind, like copy, clone certain aspects

01:27:23 and just keep replacing body parts?

01:27:27 Do you think that’s another way to achieve immortality?

01:27:30 To achieve a prolonged sort of increased longevity

01:27:33 is to replace the parts that break easily

01:27:37 and keep, because actually from your theory of aging

01:27:42 as a degradation of information,

01:27:44 so an information theory view of aging,

01:27:48 like what is the key information that makes a human?

01:27:51 Can we persist that information

01:27:53 and just replace the trivial parts?

01:27:57 Yeah, I mean the short answer is yes.

01:27:59 We’re already replacing body parts

01:28:01 but what makes us human is our brain.

01:28:03 Everything else is suboptimal except our brain.

01:28:08 The ability to replace actual neurons is really hard.

01:28:13 I think it might be easy to upload

01:28:16 rather than replace neurons because they’re so tight,

01:28:19 it’s such a network and just perturbing the system.

01:28:24 It’s Roger and Gizcat.

01:28:25 You change everything once you get in there.

01:28:28 The problem is, well, I guess the solution,

01:28:31 let me go to the solution that’s more interesting.

01:28:34 What we’re learning is that if you reverse

01:28:35 the age of nerve cells,

01:28:38 it looks like they get their memories back.

01:28:41 So the memories are not lost.

01:28:42 They’re just that the cells don’t know how to interpret them

01:28:45 and function correctly.

01:28:46 And this is one of the things we’re studying in my lab.

01:28:48 If you take an old mouse that has learned something

01:28:50 when it was young but forgotten, does it get that back?

01:28:53 And all evidence points to that being true.

01:28:56 So I’d rather go in and rejuvenate the brain as it sits

01:28:59 rather than replace individual cells,

01:29:01 which would be really hard.

01:29:03 What do you think about like efforts like Neuralink,

01:29:06 which basically you mentioned uploading,

01:29:10 are trying to figure out,

01:29:11 so creating brain computer interfaces

01:29:13 that are trying to figure out

01:29:14 how to communicate with the brain.

01:29:16 But one of the features of that is trying to record

01:29:19 the human brain more and more accurately.

01:29:22 Do you have hope for that to,

01:29:27 of course, it will lead to us better understanding

01:29:30 from a neuroscience perspective, the human mind,

01:29:33 but do you have hope for it increasing longevity

01:29:36 in terms of how it’s used?

01:29:38 I think that it can help with certain diseases.

01:29:41 But I see, at least within our lifetime,

01:29:42 that’s the best use of it is to be able to replace

01:29:45 parts of the body that are not functioning,

01:29:47 such as the retina and other parts,

01:29:50 the visual cortex back here.

01:29:51 That’s going to be doable.

01:29:53 In terms of longevity,

01:29:55 maybe we could put something on the hypothalamus

01:29:58 and start secreting those hormones and get that back.

01:30:02 Ultimately, I think the best way to preserve the brain

01:30:06 is going to be to record it.

01:30:10 But also, I think it’s going to require death,

01:30:12 unfortunately, to then do very detailed scans,

01:30:16 even if you have enough time and money, atomic microscopy,

01:30:20 and rebuild the brain from scratch.

01:30:22 Rebuild from scratch, yeah.

01:30:24 We are living more and more in a digital world.

01:30:28 I wonder if the scanning is good enough

01:30:31 for the critical things in terms of memories,

01:30:34 in terms of the particular quirks

01:30:36 of your cognitive processes.

01:30:38 They’re not, they’re not, yeah.

01:30:40 We’re not close, yes,

01:30:42 but we’ve made quite a bit of progress,

01:30:44 so if you’re an exponential type of person.

01:30:50 Yeah, well, let’s dream a little here.

01:30:52 Yes, that’s the point.

01:30:52 The way it would work, that I could see it working is,

01:30:56 so you take a single cell slice through your dead brain,

01:31:00 and we can now,

01:31:01 the problem with the engineering aspect is that,

01:31:04 the engineering is, the physical aspect of the brain

01:31:07 is not even half the problem.

01:31:09 The problem is which genes are switched on and off.

01:31:12 This experience that we’re having here

01:31:15 is altering certain genes in neurons

01:31:18 that will be preserved, hopefully, for a number of decades,

01:31:22 but you cannot see that with a microscope easily,

01:31:25 but there are technologies invented,

01:31:27 actually just down the hall in the building I’m at,

01:31:30 George Church invented a way, his lab invented a way,

01:31:33 to look at which genes are switched on and off,

01:31:36 not only in a single cell, which any lab can do these days,

01:31:40 but in situ, where it’s situated in the brain.

01:31:42 So you can say, okay, this nerve cell,

01:31:45 had these genes switched on and these switched off,

01:31:47 we can recreate that,

01:31:49 but just scanning the brain

01:31:50 and looking how the nerves are touching each other

01:31:52 is not gonna do it.

01:31:54 Wow, okay.

01:31:55 So you have to scan the full biology, the full details.

01:31:59 And look at the epigenome.

01:32:00 And the epigenome too.

01:32:01 Yeah, which genes are on and off.

01:32:03 It’s just easier to reset the epigenome

01:32:05 and get them to work like they used to.

01:32:06 True, true.

01:32:07 We’re doing that now.

01:32:08 Use the hardware we already have,

01:32:09 just figure out how to make that hardware last longer.

01:32:13 Right, ultimately information will be lost,

01:32:15 even genetic information degrades slowly through mutation.

01:32:19 So immortality is not achievable through that means,

01:32:22 though I think we could potentially reset the body

01:32:25 hundreds of times and live for thousands of years.

01:32:28 Okay, so we talked about biology.

01:32:31 Let’s, forgive me, but let’s talk about philosophy

01:32:34 for just a brief moment.

01:32:36 So somebody I’ve enjoyed reading,

01:32:38 Ernest Becker wrote The Denial of Death.

01:32:40 There’s also Martin Heidegger.

01:32:42 There’s a bunch of philosophers who claim

01:32:47 that most people live life in denial of death.

01:32:51 Sort of we don’t fully internalize

01:32:58 the idea that we’re going to die.

01:33:04 Because if we did, as they say,

01:33:07 there will be a kind of terror of,

01:33:11 I mean a deep fear of death.

01:33:15 The fact that we don’t know what’s,

01:33:17 like we almost don’t know what to do with non existence,

01:33:23 with disappearing.

01:33:24 Like our, the way we draw meaning from life

01:33:28 seems to be grounded in the fact that we exist

01:33:30 and that we at some point will not exist is terrifying.

01:33:34 And so we live in an illusion that we’re not going to die

01:33:37 and we run from that terror.

01:33:39 That’s what Ernest Becker would say.

01:33:41 Do you think there’s any truth to that?

01:33:44 Oh, I know there’s truth to that.

01:33:45 I experience it every day when I talk to people.

01:33:47 We have to live that way.

01:33:49 Although unfortunately I can’t,

01:33:51 but for most people it’s extremely distressing

01:33:56 to think about their own mortality.

01:33:59 We think about it occasionally.

01:34:00 And if we really thought about it every day,

01:34:02 we’d probably be brought to tears.

01:34:04 How much we not just miss ourselves,

01:34:05 but miss our family, our friends.

01:34:10 All living life forms have evolved to not want to die.

01:34:14 And when I mean want,

01:34:15 biochemically, genetically, physically.

01:34:18 That yeast cell, the cells that I studied at MIT,

01:34:21 they were fighting for their lives.

01:34:23 They didn’t think,

01:34:25 but our brain has evolved the same survival aspect.

01:34:28 Of course, we don’t want to die.

01:34:30 But the problem for us, unfortunately,

01:34:32 it’s a curse and a blessing is that we’re now conscious.

01:34:34 We know that we’re going to die.

01:34:37 Most species that have ever existed don’t.

01:34:40 That’s a burden, that’s a curse.

01:34:42 And so what I think has happened is

01:34:43 we’ve evolved certainly to want to live for a long time,

01:34:46 perhaps never want to die.

01:34:49 But the thought about dying is so traumatic

01:34:52 that there is an innate part of our brains.

01:34:55 And it’s probably genetically wired to not think about it.

01:35:00 I really think that’s part of being human.

01:35:03 Because, think about tribes that obsessed

01:35:06 with longevity every day and that we’re going to die.

01:35:09 They probably didn’t make much technological progress

01:35:12 because they were just crying in their huts every day

01:35:14 or on the Savannah.

01:35:16 So I really think that we’ve evolved

01:35:18 to naturally deny aging.

01:35:20 And it’s one of the problems that I face in my career.

01:35:23 And when I speak publicly and on social media

01:35:26 is that it’s shocking.

01:35:28 People don’t want to think about their age,

01:35:29 but I think it’s getting better.

01:35:31 I think my book has helped.

01:35:33 These tests that we’re developing

01:35:35 should help people understand it’s not a problem

01:35:38 to think about your longterm health.

01:35:40 In fact, if you don’t,

01:35:41 you’re going to reach 80 and really regret it.

01:35:45 And the other side of it, so again, Ernest Becker,

01:35:47 but also Viktor Frankl recommended highly

01:35:50 Man’s Search for Meaning.

01:35:52 Bernard Williams is a moral philosopher.

01:35:54 They kind of argue that this knowledge of death,

01:35:58 even if we often don’t contemplate it, we do at times.

01:36:03 And the very, what you call the curse,

01:36:06 which I agree with you, it’s a curse and a blessing

01:36:10 that we’re able to contemplate our own mortality.

01:36:13 That gives meaning to life.

01:36:16 So death gives meaning to life,

01:36:18 is what Viktor Frankl argues.

01:36:21 I would probably argue the same.

01:36:22 There’s something about the scarcity of life

01:36:25 and contemplating that,

01:36:27 that makes each moment that much sweeter.

01:36:30 Is there something to that?

01:36:32 I think it’s individual.

01:36:33 In my case, it’s completely wrong.

01:36:35 I appreciate you saying that.

01:36:39 I don’t get joy out of every day

01:36:41 because I think I’m going to die.

01:36:43 I get joy out of every day because every day is joyous

01:36:46 and I make it that way.

01:36:47 And even if I thought I was going to live forever,

01:36:50 I would still be enjoying this moment just as much.

01:36:54 And I bet you would too.

01:36:56 Well, I think about that a lot.

01:36:59 I think it’s very difficult to know.

01:37:03 I’m almost afraid that I wouldn’t enjoy it as much

01:37:06 if I was immortal.

01:37:07 I’m almost afraid to want to be immortal or to live longer

01:37:11 because it perhaps is a kind of justification

01:37:18 for me to accept that I’m going to die.

01:37:21 It’s saying like, oh, if I was immortal,

01:37:23 I wouldn’t be able to enjoy life as much as I do.

01:37:26 But it’s very possible that I would enjoy just as much.

01:37:30 Of course, enjoying life, whether you’re immortal or not,

01:37:34 takes work.

01:37:35 Like it requires you to have the right kind

01:37:38 of frame of mind.

01:37:39 You can discover, you can focus your mind

01:37:42 on the ugliness of life.

01:37:44 There’s plenty of ugly things in this world

01:37:46 and you can focus on them.

01:37:47 You can complain.

01:37:49 Whenever like, you know, if it’s raining outside,

01:37:53 you can focus on the fact that you have shelter

01:37:56 and enjoy the hell out of it.

01:37:58 Or you can enjoy running in the rain when it’s warm

01:38:02 and the beauty of nature, just being one with nature.

01:38:05 Or you can just complain, it’s fucking weather again

01:38:07 in Boston and then it’s either always raining

01:38:10 or freezing, damn it.

01:38:13 The same thing with like wifi going out on airplanes.

01:38:18 You can either complain about stupid wifi

01:38:23 on JetBlue or something.

01:38:25 Or you could say like, how incredible it is

01:38:27 that I can fly through the sky and in a matter of hours

01:38:30 be anywhere else in the world.

01:38:31 And then I could also on occasion watch like check email

01:38:35 and even watch movies while connecting through satellites

01:38:39 that are flying through space.

01:38:40 So it’s a matter of perspective and perhaps

01:38:42 there’s an extra level of work required

01:38:44 when you’re immortal because it’s easier

01:38:47 when you’re immortal or live longer to be lazy,

01:38:51 to delay stuff.

01:38:52 But if you’re not, you can still derive

01:38:55 the same amount of joy.

01:38:56 It’s possible, it’s possible.

01:38:59 It’s definitely possible.

01:38:59 In my life, I went from being the nothing’s working

01:39:03 to every day’s great to wake up to.

01:39:06 And I think even if you think you can live forever,

01:39:10 you can enjoy every day.

01:39:12 What I do is everything’s relative.

01:39:14 We can compare ourselves to our neighbor who has more money

01:39:17 or to the flight that should have had wifi

01:39:20 or which is what I do, I’m still six years old remember.

01:39:23 What a six year old does says, look, I can,

01:39:27 when I tell my fingers to form a fist,

01:39:29 they actually do that.

01:39:31 That’s really cool.

01:39:32 That’s how I live my life.

01:39:34 I can pick up on your desk here, this metal object.

01:39:36 It’s a metal cube, about an inch by an inch by an inch.

01:39:39 And I tell myself not about cubes,

01:39:42 but about inanimate objects.

01:39:44 Probably once a day I’ll say, I’m a living thing.

01:39:48 I can think, I can move, I can eat, I am full of energy.

01:39:51 And there’s that leaf or this cube here

01:39:53 that will never be alive.

01:39:55 That’s what I look at and compare myself to.

01:39:59 And for as long as I live, if it’s forever,

01:40:01 of course it won’t be, but even if it was forever,

01:40:04 relative to this lump of metal on this table here,

01:40:07 we are wondrous things in the universe

01:40:10 and probably the most wondrous things in the universe.

01:40:13 Yeah, we’re able to deeply appreciate the leaf or the cube

01:40:18 and deeply appreciate ourselves,

01:40:20 which is, it can be a curse, but it’s mostly a gift,

01:40:24 especially when you’re, it’s such a beautiful poem.

01:40:29 Now I’m six, I’m as clever as clever,

01:40:31 so I think I’ll be six now forever and ever.

01:40:35 That’s a good thing to aspire to.

01:40:37 Your grandmother was onto something.

01:40:40 David, this is an incredible conversation.

01:40:43 I’m a huge fan of your work.

01:40:44 So thank you for wasting your valuable time with me today.

01:40:49 I really, really appreciate it.

01:40:50 This was awesome.

01:40:51 Thank you for having me on, Lex, appreciate it.

01:40:53 Thanks for listening to this conversation

01:40:55 with David Sinclair, and thank you to Onnit, Clear,

01:40:59 National Instruments, Simply Safe, and Linode.

01:41:03 Check them out in the description to support this podcast.

01:41:07 And now let me leave you with some words

01:41:08 from Arthur Schopenhauer.

01:41:10 All truth passes through three stages.

01:41:13 First, it is ridiculed.

01:41:15 Second, it is violently opposed.

01:41:18 Third, it is accepted as being self evident.

01:41:22 Thank you for listening, and hope to see you next time.