David Sinclair: Extending the Human Lifespan Beyond 100 Years | Lex Fridman Podcast #189
the following is a conversation with david sinclair he is a professor in the department of genetics at harvard and co-director of the paul f glenn center for the biology of aging at harvard medical school he's the author of the book lifespan and co-founder of several biotech companies he works on turning age into an engineering problem and solving it driven by a vision of a world where billions of people can live much longer and much healthier lives quick mention of our sponsors on it clear national instruments and i simply safe and lino'd check them out in the description to support this podcast as a side note let me say that longevity research challenges us to think how science and engineering will change society imagine if you can live a hundred thousand years even under controlled conditions like in a spaceship say then suddenly a trip to alpha centauri that is uh 4.37 light years away takes a single human lifespan and on the psychological maybe even philosophical level as the horizons of death drifts farther into the distance how will our search for meaning change does meaning require death or does it merely require struggle reprogramming our biology will require us to delve deeper into understanding the human mind and the robot mind both of these efforts are as exciting of a journey as i can imagine this is the lex friedman podcast and here is my conversation with david sinclair i usually feel like the same person when i was 12 like when i right now as i think about myself i feel like exactly the same person that i was when i was 12 and yet um i am getting older both body and mind and still feel like time hasn't passed at all do you um feel this tension in yourself that you're the same person and yet you're aging yeah i have this tension that that i'm still a kid but that helps in my career scientists need to have a wonder about the world and you don't want to grow up 12 year olds and even younger i would say 6 7 year olds i've still got that boy in me and i can look at things it's a gift i think that i can see things for the first time if i choose to and then explain them as i would to a 60 or 6 year old because i i am that mentally but on the other hand i'm getting older right i run a lab of 20 people at harvard i've got a book i've got uh you know science to do companies to run and so i have to and on most days just pretend to be a grown up and and be mature but i definitely don't feel that way there's uh there's something i really appreciated in opening your book you talked about your grandmother and on this kind of theme on this kind of topic uh she first of all had a big influence on you my grandma mother had a big influence on me he also mentioned this poem by the author of winnie the pooh allen alexander milne maybe i can read it real quick because i on the topic of being children when i was one i had just begun when i was two i was nearly new when i was three i was hardly me when i was four i was not much more when i was five i was just alive but now i am six i am as clever as clever so i think i'll be six now forever and ever um so this idea of being six and staying six forever being youthful being curious being childlike this and other things what uh influence has your grandmother had in your thinking about life about death about uh love yeah i was getting misty-eyed as you read that because that that poem was read to me very often if not every day by my grandmother who partially raised me and she was as much a bohemian as an artist philosopher and she's one of those people that wouldn't talk about the little things she said i hate small talk don't talk to me about politics or the weather yeah talk to me about human beings and culture so i was raised on that and this poem was one that she read to me often because she knew that the mind of a child is precious it's honest uh it's pure and she grew up during the second world war and in hungary and budapest witnessed the worst of humanity she was trying to save a whole group of jewish friends in her apartment saw what happened after the world war which was um there was the the russians were in control and locals weren't necessarily treated well if they were rebellious which she was and then there was the revolution in 56 which she was part of and had to escape the country so she saw what can happen when humans do their worst and her words to me expressed in part through that poem was david always stay young and innocent and have wonder about the world and then do your best to make humanity the best it can be and that's who i am that's what i live for that's what i get up in the morning to do is to leave the world a better place and show to whoever's watching us whether it's aliens or some future human historian that we can do better than we did in the 20th century you know we mentioned offline this idea of bringing people back to life through um through artificial intelligence sort of i don't know if you've seen videos of basically animating people back to life meaning uh whether it's for me personally i've been working on specifically about albert einstein but also alan turing isaac newton and richard feynman and it's it's an opportunity to bring people that meant a lot to others in the world and uh animate them and be able to have a conversation with them at first to try to visually visually explore the the full richness of character that they had as they struggle with the ideas of the modern age sort of it's less about bringing back their mind and more bringing back the the visual quirks that made them who they are and then maybe in the future it's using the textual the visual the the the video the audio data to actually compress down the person for who they are and be able to generate text there's a few companies there's replica which is a chat engine that was born out of the idea of bringing the the founder uh lost her friend uh to uh he he got ran over by a car and the initial reason she founded the company was trying to just have a conversation with her friend she trained a machine learning uh natural language system on the text that they exchanged with each other and try she had a conversation with him sort of after he was gone uh and it's very the the conversation was very trivial it was obvious that it's uh you know a ai agent but it gave her solace it made her actually feel really good and that's the way i wonder if it's possible to bring back people that are that means something to us personally not just einstein but people that we've lost and in that way achieve a kind of small artificial immortality i don't know if you think about this kind of stuff uh well i'd definitely think about a lot of things that that one's a really good one there's a great black mirror episode about the the wife who brings back the the boyfriend or husband i think one of the challenges with bringing back richard feynman would be to to capture his sense of humor but that would be awesome um but yeah bringing back loved ones would be great especially if uh if it's you're they're young and uh they die early though it may hold you back from moving on that's another thing that could happen as a negative but i think that's great and i also think that it's going to be possible especially when we're recording some of us every aspect of our lives whether it's our face or uh things we see right eventually one day everything we see can be recorded and then you can you can build somebody's experience and and thoughts uh speech and and you will have replicas of everybody um at least digitally and physically you could do that too one day but that that's a good idea especially because there are people that i'd like to meet and i think it's easier than building a time machine one person i'd love to meet is benjamin franklin really well i wouldn't go back in time um i would but i'd prefer to bring him into the future and say can you believe we have this thinking machine in our pockets now and he just see the look on his face as to where humanity has come because i think of him as a modern guy that just was before his time yeah so you're you're thinking benjamin franklin the scientist not benjamin flanken the political thing because he'd be very upset with congress right now right so maybe talk to him about science and technology not uh not politics or maybe just don't get him on twitter because he'll be very upset with human civilization you know i wonder what their personalities are like isaac newton it does seem complicated to figure out what their personality is like even friedrich nietzsche who i also thought about feynman is we just have enough video where we get the full kind of um i mean it shows you how important it is to get not the official kind of book level presentation of a human but the authentic the full spectrum of humanity you mentioned collecting data about a person collecting the whole thing the whole of life the ups and downs the embarrassing stuff the beautiful stuff not just the things that's condensed into a book and then with finding you start to see that a little bit through conversations you start to see peaks of like that genius and then through stories about him from others and then certainly you uh the sad thing about alan turing for example is there's very little if any uh recording of him in fact i haven't been able to find recording allegedly there's supposed to be a recording of him doing some kind of radio broadcast but i haven't been able to find anything and so that that's that's that's truly sad that it feels like it makes you realize how the upside how nice it is to collect data about a person uh to capture that person there's that's the upside of the modern internet age the digital age that that information uh yeah creates a kind of immortality the and then you can choose to highlight the best parts of the person maybe throw away the ugly parts and celebrate them even after they're gone so that's a really interesting opportunity you um you've also mentioned to me offline that you're really excited about all the different wearables and all the different ways we can collect information about our bodies about uh well the whole thing is what's most exciting to you in terms of collecting the the biological uh data about a human being well so i'm a biologist i find animals and humans as machines very interesting it's one of the reasons i didn't become an engineer or a surgeon i wanted to understand how we actually are built and so i think a lot about machines merging with humans and the first of that are the bio wearables and so i talked a lot about this i wrote about it um in life span the book and pictured a future where you would be monitored constantly so that you wouldn't suddenly have a heart attack you'd know that was coming or you you wouldn't go to the doctor and they don't know if it's you need an antibiotic or not um long term how old are you how to fix things what should you eat what should you take what should you do these devices i predicted would be smarter better educated than you than your physician and would augment them and then there'd be a human that would just tick off to see if that it's correct and they approve i also was predicting in the book that we would have video conferences with our doctors and that medicines would be delivered initially by courier but eventually by drones and get it to you sometimes in an emergency and that we could even have pills that were synthesized or delivered um in your kitchen and combined certainly what's amazing about that is that what are we now two years since the book came out even less and that future is basically here already covered uh 19 accelerates accelerated that incredibly so where we're at now in society is if you if you want to pay for it you can have a blood test that will detect cancer 10 20 years earlier than it would before it forms a tumor you can of course do your genome very cheaply for less than a hundred dollars now there are bio wearables already i wear this ring from aura that i have number of years of data i've been doing blood tests for the last 12 years with a company called inside tracker which i consult for and so i have all of that data as well and there's 34 different parameters on my testosterone my blood glucose my inflammation and i use all that data to of course i wear a watch that that measure things as well i use that data to keep my body in optimal shape so i'm now 51 and according to those parameters i'm at least as good as someone in their early 40s and i if i really work at it i can get my biochemistry down to early to mid 30s though i like to you know now eat a little dessert once in a while so that's the future we're in right now anyone can do what i just said but in the very near future just in the next few years you can be wearing wearables so i'm currently wearing a little what's called a bio sticker uh this one i just put on last night uh it's about an inch long a few millimeters yeah people just listening it's uh san diego's chest yeah it's just the how does it attach it's just kind of it sticks on sticks yeah so on one side you have an on button that you press the lights come on flashes four times it's good to go it immediately syncs to your phone and this one uh the it's called a bio button a nice name and there's a there's another one that i have that i haven't tried yet that does ekg on your heart um this is mainly for doctors to monitor patients that go home after a heart attack or surgery but that's medical grade fda approved device so there will be a day in fact it's already here that doctors are using these to get patients to go home and save a week in hospital two thousand dollars at least for each patient that's massive safe um savings for the hospital but ultimately what i'm excited about is a future that isn't that far off where everybody certainly in developed countries eventually these will cost a few cents and rechargeable the only cost will be the software subscription that can be monitored constantly and to give an idea what this is measuring me at a thousand times a second is my vibrations as i speak my orientation it can already has told me this morning how i slept where i slept what side i slept on uh we've got sneezing coughing body temperature heart rate heart of other parameters of the heart that would indicate heart health these these data are being used to now to predict sickness so eventually we'll have just in the next year or so the ability to predict whether something or diagnose whether something is pneumonia or just a rhinovirus that can be treated or not right this is really going to not just revolutionize medicine but i think extend lives dramatically because if i have if i'm going to have a heart attack next week and that's possible this device should know that and i'll be in hospital before i even have it maybe you can talk a little bit about inside tracker because i saw that there's some really cool things in there like it actually so maybe you can talk about i guess that you're collecting blood and to give it the data so and it has like basic recommendations on how to improve your life so we're not just talking about diseases right like anticipating having a particular disease but it's almost like guiding your trajectory to life how to whether it's extend your your life or just live a more fulfilling like improve the quality of life i suppose this is the right way to say it what how does inside tracker work uh what the heck is it because i thought there was also pretty cool yeah what is it is it something other people can use you can definitely use it uh you can sign up it's consumer it's like a company consumer facebook company it is yes uh and i also want to democratize the ability to to just take a mouth swab eventually we don't need to have a blood test necessarily but for now it's a blood test and and you'd go to a lab core request in the u.s it's also available overseas you can upload your own data for a minimal cost and get the algorithms the ai in the background to take that data plot where you are against others in your age group as in terms of health and longevity by your age they call it no inner age but also it provides recommendations and this isn't just a bunch of bs it sounds like it might be to say i'll go eat this or go to that restaurant and order that but it's actually based on they basically this company has entered hundreds now it would be thousands of scientific papers into their database and hundreds of thousands of human data points and they have tens of thousands of individuals that have been tracked over time and anonymously that data is used to say what works and what doesn't if you eat that what works if you take that supplement what works and i was a co-author on a paper that showed that the recommendations for food and supplements um was better than the leading drug for type 2 diabetes that's so cool the idea that you can connect like skipping the human having to do this work you can connect the scientific papers almost like meta-analysis of the science connected to the individual data and then based on that sort of connect your data to whatever the proper group is within the whatever the scientific paper is to make the suggestion of how how like how that work applies to your life and then that ultimately maps to like a recommendation what you should do with your life like it all like this giant system that ultimately recommends you should drink more coffee or less right and and we'll have the genome in there as well you can upload that yeah uh and so so these programs will know us way better than we do and and our doctors as well the idea of going to a doctor once a year for an annual checkup and having you know males get a finger up their butt and uh you know you cough that that to me is a joke that's medieval medicine and that's very soon going to be seen as medieval yeah it's um to me as a computer science person it's always upsetting to go to the doctor and just look at him and like realize you know nothing about me like you you're you're you're making your like opinions based on like it is very valuable years of intuition building about basic symptoms but you're just like it is medieval they're very good at it in fact doctors in medieval times are probably damn good at working with very little but the thing is i'd rather pref for a doctor that doesn't really know what they're doing but has a huge amount of data to work with well you're right and many of my good friends are doctors i work at hard so i'm not against the profession at all yeah but i think that they need just as much help as anyone else does we wouldn't drive a car without a dashboard we wouldn't think of it so why would doctors do the same if we could we step back to the big profound philosophical both tragic and beautiful question about age how and why do we age is it uh from an engineering perspective he said you like the biological machine is that a feature or a bug of the biological machine it is both a bug and a feature uh evolutionary speaking we only live as long as we need to to replace ourselves efficiently if you're a mouse you're only going to live two and a half years three years you're probably going to die of starvation predation freezing in the winter so they they divert most of their resources to reproducing rapidly but they don't put a lot of energy into preserving their soma which is their body conversely a baleen type of whale a bowhead whale in particular will live hundreds of years because they're at the top of the food chain and they can live as long as they want so they breed slowly and build a body that lasts we're somewhere in between because we've you know we've really only just come out of the savannas where we could be picked off by a cat we were pretty wimpy going back six million years ago uh so we we actually need to evolve quicker than evolution will and that's why we can use our oversized brains and intuition to give us what evolution not only didn't give us but took away from us you know we're pathetic look at our bodies these arms if any of us even the strongest person in the world went in a cage with a chimpanzee the chimp could knock that person's head off no question so we're pathetic so we need to engineer ourselves to be healthier and longer lived so getting to aging we we can do better right whales do way better we're trying to learn how whales do that and if you ask really anybody in the field now professor they'll say there are eight or nine hallmarks of aging which are really it's a it's a word for causes of aging so that you probably have heard of some of these your listeners will have a loss of telomeres the ends of the chromosomes like their little ends of um shoelaces that kind of thing they get too short cells stop dividing becomes senescent they they become they put out what are called mitogens that cause cancer and inflamma inflammatory molecules that's another aspect of aging cellular senescence another one is loss of the energetic so mitochondria the battery packs wind down there's a whole bunch stem cells proteostasis well these are our achilles heels that i'm talking about that are common amongst all life forms really but if you wanted me to jump to the chase as to where what is the upstream defining factor if we boil it down what do we get so most biologists would say you can't boil it down it's too complex i would say you can boil it down to an equation which is the preservation of information and lost due to entropy i.e noise and that is the basis of my research it originally came out of discoveries in yeast cells where i went to mit in the 1990s you studied bread i kind of did i studied the uh the makers of bread a little yeast called saccharomyces cerevisiae which at the time was one of the hottest excuse the pun uh organisms to work on yes but they we we figured out in the lab why yeast cells get old and found genes that control that process and made them live longer which was an amazing four years of my life one of those genes had a name with an acronym sir2 now the two is irrelevant the s-i-r is important and the most important letter out of all of those three is i which stands for information silent information regulator number two when you put more copies of that gene in just put in one more copy the yeast cells lived 30 longer and suppressed the cause of aging which was the dysregulation of information in the cell and then so fast forward to now i've been looking in humans and mice because they live shorter and cheaper to study where the loss of information in our bodies is a root cause of aging and i think it is your boldness in viewing biology in this way is fascinating because that also leads to a kind of uh it's almost like allows for a theory of aging like like you could boil it down to a single equation and it leads to a perhaps a metric that allows you to optimize aging sort of in the fight against entropy to figure out which mechanisms like you said the the silent information regulator which mechanisms allow you to preserve information now without like without injecting noise without without creating entropy without creating degradation of that information for some reason converting biology which i thought was mostly impossible into an engineering problem feels like it makes it amenable to optimization to solving problems to creating technology that can whether that's genetic engineering or ai it makes it uh possible to uh create the technology that would improve the the degradation of information and aging is there more concrete ways you think about the kind of information we want to preserve and also is there good ideas about regulators of that information about ways to prevent the distortion and degradation of that information right so that we have some information regulated genes in our bodies we have seven of them uh certain one through seven they're called and we found in in mice one way to slow down the loss of information is to just give more of these um to up regulate these genes so we we made a mouse that has more of this so t1 gene turned it on and that slowed down the aging of the brain and preserved their information now what information am i talking about you might ask well again you can simplify biology there are two types of information in the cell primarily the one we all read about and know about is the dna the genome and that's base four information atcg the four chemicals that make up the various sequences of the genome billions of letters and that also degrades over time but what's been fascinating is that we find that that information is pretty much intact in old animals and people you can clone a dog one of my friends in l.a just cloned his dog three times so this is doable right it means that the genome can be intact but what's the other type of information it's the epigenome the regulators of the genetic information and physically that's really just how the dna is wrapped up or looped out for the cell to access it and read it so it's similar to an excuse this analogy but it's a good one um a compact disc or a dvd those pits in the foil are the digital information that's the genome and the epigenome is the reader of that information and in in a different cell you'd read different music different songs different symphonies and that's what gets laid down when we're in the womb and that gives makes a skin skin cell forever a skin cell and not a brain cell tomorrow thank god otherwise our brains wouldn't work very well but over time what we see is that the brain cells start to look more like skin cells and the kidney cells start to look more like liver cells and they what we call x differentiate this is a term that we use in my lab but isn't yet widely used but we needed a term to explain this and that those that process of x differentiation the loss of the reader of the the cd or the dvd we liken that to scratches on the dvd so that the reader cannot fully access the information now we can slow down the scratches as i mentioned we can turn on these genes we can even put in molecules into the cell or even eat them and turn on those pathways which which my father and i have been trying to do for about a decade to slow things down but the question that i've had is is there a repository of information still in the body because anyone who knows anything about the loss of information or even has tried to copy a cassette tape or photocopy or xerox anything knows that over time you you lose that information irreparably so i've been looking for a backup copy inspired largely by claude shannon's work at mit as well in the 1940s his theory mathematical theory of communication is just brilliant and so i've been looking for what he called the observer which is the backup copy we today might call that the tcpi pro tcp ip protocol of the internet that stores information in case it doesn't make it to your computer it will fill in the gaps and we've been spending about the last five years to try and find if there really is a backup copy in the body to reset the epigenome and polish those scratches away that's incredible so finding the backup so whenever there are too many scratches pile up you can just write a new version like right that not every new version but go to the backup and restore it right that's really all we're talking about it's not that hard once you know the trick and for people that actually remember uh like dvds and scratches on them how frustrating it is that that's a brilliant metaphor for aging and then the the reader is uh is the thing that skips and then it could destroy your experience the richness of the experience that is uh listening to your favorite song right but in biology it's even worse because you'll lose your memory your kidneys will fail you'll you'll get diabetes your heart will fail and we call that aging and age-related diseases so it's it most people forget that diseases that we get when we get old are 80 to 90 caused by aging and we've been trying to fix things with band-aids after they occur without even generally talking about the root cause of the problem is there um the scratches do those come from are those programmed or are they failures meaning is it so if it's by design then there's like a encoded timeline schedule that the body's just on purpose degrading the whole thing and then there's the just the wear and tear of like the scratches and a disc that happen uh through time which which one is it that's the source of aging uh it's more akin to wear and tear there isn't a program um getting back to evolution there's no selection for aging we're not designed to age we just live as long as we need to and then we're at the whim of entropy basically second law of thermodynamics stuff falls apart we live a bit longer than age 40 only because there are robust resilient systems but eventually they fail as well current limit to the human lifespan where they completely fail is 122. uh but so it's and i but i don't like to think of it as wear and tear because there's there's two aspects to it there's a system that's built to keep us alive when we're young but actually ghost comes back to bite us as we get older and we call this this issue antagonistic pleiotropy what's good for you when you're young can cause problems when you're older so we've been looking what what is the cause of the main causes of the noise and we've come we found two of them definitively the first one is broken chromosomes when a chromosome breaks the cell has to panic because that's either going to cause a cancer or kill the cell there's only two outcomes it's pretty much a problem uh and so what the cell does is it reorganizes the epigenome in a massive way what that leads to is think of it as a tennis match or a ping pong game the proteins are the bowls and they now leave where they should be which is regulating the genes that make the cell type whatever it is and they have to they have a dual function they actually go to the break the chromosome will break and fix that and then they come back you might ask well why is it set up that way well it's a beautiful system it coordinates gene expression the control systems with the repair you want them coordinated problem is as we get older this ping pong game some of the balls get lost they don't come back to where they originally started uh and that's what we think is the main noise for aging and we've also the other cause of aging that we found is is cell stress we damage nerves and they age rapidly so you that's the other issue there's probably others smoking chemicals for example we know accelerates biological age pretty dramatically but the question is can you slow that down or can you reset them to get those ping-pong balls to go back to where they originally started in the game and we think we've found a way to do that what can you give me hints uh whose fault is it and the ball's not coming back is it the proteins themselves like are they are they starting again i've been obsessed with the protein folding problem from the ai perspective so is it the proteins or is it something else well we know who hits the balls um and recruits them so that the brake uh is recognized by proteins who send out a signal uh through phosphorylation is typical way cells talk to other proteins and that recruits those repair factors those ping-pong balls to the brake so the cell's actively doing this to try and help itself but we don't know who's to blame for them not coming back um that could just be a flaw in the quote-unquote design i don't think that there's something saying well one percent of you you bowls proteins never go back i just think it's hard to reset a system that's constantly changing we have in our bodies close to a trillion dna breaks every day and imagine that over 80 years what damage that does to our epigenomic information now we know that this is well i should we never know anything in biology but we have strong evidence that this is true because we can mess with animals we can create dna breaks and tickle them with a few breaks maybe raise it by threefold over background levels of normal breakage and if we're right those mice should get old and they do we can actually we've we've created these breaks in a way that's titratable we can it's like a rheostat we can send it to 11. you know i drove my tesla here i'm a big fan of of spinal tap two going to 11. if we go to 11 we can make a mouse old in a matter of months we prefer to go to a level of about four and it gets old in 10 months but it's definitely old it's got all of the hallmarks of aging it's got diseases it looks old its skin is old it's got gray hair but importantly we can now measure age by looking at the scratches we can look at the epigenome we can measure it and use machine learning to give us a number and those mice are 50 older than normal so you can replicate the aging process in a controlled way you can all i mean in a way that you i mean you could accelerate it in a controlled way and measure how much exactly it's aging and that gives you step one of a two-step process to when you can then figure out what how can we reverse this and now we're reversing those mice is there a good i love what you said i mean in biology you really don't know it's it's such a beautiful mess uh is is there is there ideas how to do that is that on the genetic engineering level is that uh like what can you mess with is it going to the trying to discover the backup copies and restoring from them like what's if it's it's possible to convert it into natural language words what are the ideas here what is the observer and how do we contact it exactly what's the observer and how do you contact or if there's other ideas how to reverse the the the boss getting lost process yeah well you you can slow it down slow it but we found a reset switch recently we just published this in the december 2020 issue of nature and what we found is that there are three embryonic genes that we could put into the adult animal to reset the age of the tissues and it only takes four to eight weeks to work well and we can take a blind mouse that's lost its vision due to aging neurons aren't working well towards the brain reset those neurons back to a younger age and now the mice can see again these three genes are famous actually because they're a set of four genes discovered by shinya yamanaka who won the nobel prize in 2016 for discovering that those four genes when turned on at high levels in adult cells can generate stem cells and this is i think well known now that we can create stem cells from adult tissue but what wasn't known is can you partially take age back without becoming a tumor or generating a stem cell in the eye which would be a disaster and the answer is yes there is a system in the body that can take the age of a cell back to a certain point but no further safely and reset the age and uh we're now using that to reset the age of the brain of those mice that we age prematurely and they're getting their ability to learn back this is really exciting right like what's uh what's the downside of this well the downside is if you overdo it and you don't get it right uh you might cause tumors but we do we do it very carefully and we also know that in the eye it's very safe yeah we also injected these we deliver them by viruses so we can control where and when they get turned on and in this paper we've published that if we put high levels in the mouse into their veins throughout the body they don't get cancer for over a year so i'm so optimistic that we're going into human studies in less than two years from now is there a place where ai can help sorry to inject one of the things i'm very excited about i'm passionate about so uh deep uh google deep mind recently had a big breakthrough with alpha fold two but also half a fold two years ago with um achieving sort of uh state-of-the-art performance on the protein folding problem single protein folding but it also paints a hopeful picture of what's possible to do in terms of simulating the folding of proteins but also simulating biological systems through ai is there something to you combined with this brilliant work on the biology side that you're hopeful about where ai can be a tool to help where isn't that a tool and if you're not using ai right now in biology you're getting left behind we use it all the time we're using it to generate these biological clocks to be able to read those scratches we're using it to predict the folding of proteins so we can target molecules and modulate their activity we're using it to assemble genomes of different species what else we use it to predict the longevity of a mouse based on how it reacts to certain things hearing eyesight generally frailty so we have we just put out a paper last year on that um the other thing we can use it for which is a little off the track here but we use it for predicting which microorganisms are in your body actually not predicting telling you so our daughter natalie was infected with lyme disease a few years ago almost went blind from it and the test took four days and i thought just give me the dna for my spinal fluid i'll go tell you what's in it if it's lyme disease or not they refused and so at that point i said this has to be done better so i've started a company that now can take a sample of any part of your body it's typically done now with transplant liver transplant patients to detect viruses that come out of their organs but that's that's another area that ai is extremely important for um i i think if you're not in five years if you're not using you know deep learning you've got a problem because the amount of data that we generate now as biologists is just terabytes can be terabytes per week it'll eventually be terabytes per day and then we just go from there and i actually have trouble recruiting enough bioinformaticians a lot of our work is now just number crunching a part of that is collecting the data which is kind of something we've talked a little bit about but is there something you can say about how we can like can collect more and more data not just on the one person level like for you to understand your like various markers but to create huge data sets to understand how we can detect certain pathogens detect certain properties characteristics of whether it's aging or all the other ways the human body can fail it seems like with the with biology there's a kind of privacy concerns that well actually not privacy concerns it's almost like regulation that kind of prevents like hospitals and sharing data um you know i'm not sure exactly how to say it but it seems like when you look at autonomous vehicles people are much more willing to share data when you look at human biology system people are much less willing to share data is there a hopeful path forward where we can share more and more data at a large scale that ultimately ends up helping us understand the human body and then treat problems with the human body so we are right in the middle we're living through what's going to be seen as one of the biggest revolutions in human health through the gathering of data about our bodies and 20 years ago people didn't want to go on social media they're worried about it now you have to if you're a kid that's for sure same with medical records these are becoming all digitized and and expanded ultimately we're going to even if we don't want to have to be monitored there's going to be a court case that i bet two three years from now someone's going to say how come my father died from a heart attack you had these biosensors 20 bucks and you didn't use it lawsuit right there and suddenly all hospitals have to give you one of these there will be a reversal like to where it's your fault if you don't collect the data that's brilliant that's and that's absolutely right i mean that's absolutely right that's the frustration i feel when going to the doctor is like you're it's almost negligent to not collect the data because you're making if there's something really wrong with me and you're making decisions based on very few tests that's almost negligent when you have the opportunity to collect a huge amount more data well like let me tell you something yeah like the i've got this inside tracker data for for myself over a decade and you'd think my doctor would roll his eyes at this oh he's gone to a consumer company blah blah blah i had my first checkup in a year with him through video conference and he was running blind he really didn't know what was going on with me he asked the usual things how am i sleeping how am i eating these kind of usual things and i said well i've got new tests back from inside tracker and he said great i'd love to see them so i share screen and we look at the graphs look at the data and he's loving it because he cannot order these tests willy-nilly so i said well let's order a hba1c blood glucose levels because i'm very interested in that that tracks with longevity and he says well i have no reason to order that do you have a family history no uh are you have any symptoms of diabetes no well i can't order the test i almost wanted to reach through the computer and strangle him um but instead you know i i pay a little bit to get these tests done and then he looks at them so that's now the way consumer health is going is that you can get better data than your doctor can and but they like you to do that quick human question maybe you can educate me i've i think doctors sometimes have a little bit of an ego i understand that the doctor is super experienced a lot of things but this is a fundamental question of human variability like i know a lot of specific details about like um i mean depending of course what we're talking about but there's a i bring a lot of knowledge and if i have data with me then i have like several orders of magnitude more knowledge and i think there's an aspect to where the doctor has to put their expert hat like take it off and actually be a curious open-minded person and study and look at that data do you think it's possible to sort of change the culture of the medical system to where the doctors are almost as you said are excited to see the data or that's already happening it's really happening now we've probably lost the last generation um that they're no hopers but so i teach at harvard medical school and they're excited about this they're excited about aging which is a new aspect to medicine oh wow we can do something about that and then yeah all this data what do we do with it there's still the traditional pathology and all that stuff which they need to know but time will change their their uh mindset i'm not worried about that and like we were discussing this isn't a question of if it's just a matter of when and it's you know i have a front row seat on all of this i had breakfast with with the ceo who uh is making this happen uh just yesterday i can tell you for sure that most people have no idea that this revolution is occurring and is happening so quickly uh if you're running a hospital and you can save two thousand dollars per cardiac patient what are you gonna do you have to use it otherwise you know the hospital down the road's gonna be beating you um and there are large hospital aggregations so there's ascension and others that just have to go this way for budgetary reasons and right now the u.s spends what is 17 of their gdp on healthcare for let's say one of these buttons on my chest cost 20 bucks it's rechargeable and it can predict people's health and save on antibiotics prevent heart attacks how many billions if not trillions of dollars will that save over the next decade yeah so when the public wakes up to this they'll almost demand it like this this should be this should be accepted everywhere this is obvious it's gonna save a lot of money it's gonna improve the quality of life well and the cfos of hospital yeah groups will have to and insurance companies are going to want to get in on this so now that gets to privacy right if should an insurance company have access to your data i would say no but you could voluntarily show them some of it if they give you a discount and that's also being worked on right now i hope we do create kind of systems where i can volunteer to share my data and i can also take the data back meaning like delete the data request the deletion of data and then maybe policy creates rules to where you can share data you could delete the data and i think if i have the option to delete all my data that that a particular company has then i'll share my data with everyone like i feel like uh if the if uh because that gives me the tools to be a consumer an intelligent consumer of giving of awarding my data to a company that deserves it and taking it back when the company is misbehaving and in that way encourage as a consumer in the capitalist system encourage the companies that are doing great work with that data well yeah health care data security is is number one on on my mind uh inside tracker made sure that that was true but you know these buttons on your chest there's very private stuff they can probably tell if you're having sex one night right so this is not the kind of stuff you want leaked yeah so i don't know whether it's blockchain or just for yourself i don't want this public life i guess it depends on how you how how you go but yeah uh you know there there's a lot of stuff you don't want out there and this definitely has to be number one because it you know it's one thing to have your credit card information stolen it's another thing health records are permanently out there yeah so there's on the biology side super exciting ways to um to slow aging but there's also on the lifestyle side i've recently did a 72 hour fast it's just an opportunity to take a pause and be you know appreciate life think about like there's something about fasting that um encourages you to reflect deeper than you otherwise might the time kind of slows and you also realize that you're human because your body needs food and you start to see your is almost as a machine that that takes food and produces thoughts and then and then ends briefly i mean there you start to depending who you are if you're like engineering minded you start to think of this whole thing as a kind of yeah as a machine and then also feelings fill this machine uh feelings of gratitude of love but also the uglier things of jealousy and greed and hate and all those kinds of things you start to think okay how how do i manage this body to create a rich experience all that comes from fasting for me anyway but there's also health benefits to fasting i intermittent fast a lot i eat just one meal a day most of the time is there something you can say about the benefits of fasting in your own life and in general the anti-aging process well you're a philosopher too sorry i apologize no i'm impressed uh through renaissance man uh it's it's a joy to be here uh so when it comes to fasting this is you know being abstinence is one of the the oldest ways to improve health right probably they knew this 5000 plus years ago so that's not new but what we're figuring out is what is optimal and how does it work and one of the things we helped contribute to which i can speak to with some authority is that these longevity genes we work on we showed back in the early 2000s are turned on by fasting and at least in yeast we were the first to show that how calorie restriction fasting works to extend lifespan that was the first for any species something similar happens in our bodies when we're hungry or put our bodies under any other perceived adversity such as running our bodies think wow we're getting run chased by a cyber save tooth cat or something if we're really hot or cold these probably also work to put our bodies in this defensive state to activate these genes in the way that whales do and mice don't and so hunger is the best way to do that in fact i don't think you have to feel hungry you can get used to it but if there was one thing i would recommend to anybody to slow down aging would be to skip a meal or two a day now it doesn't mean you don't have to live well you can go out i go to restaurants i eat regular food i try to be as healthy as possible but i've gone from skipping breakfast most of my life now to skipping lunch as well and i have my physique back that i had when i was 20. i feel 20 mentally i'm much sharper i don't feel tired anymore i sleep well so i'm a huge fan of the one meal a day thing uh where i'm not good at is going beyond one day but have you ever fasted longer than uh than them 24 hours i tried doing two days i might have made it to the third and given up i'm i just find that i'm i'm not ver i don't have a lot of willpower i also hate exercise so i'm not sure how long i'm going to live but i've managed to do one meal a day so if i can do that seriously anybody can do that um to your listeners and viewers i would say don't try to do it all at once you can't go from snacking and eating three meals a day to what i do easily work your way up to it but also compensate with drinking if you like tea if you like coffee put some milk in it um that's fine you can fill your stomach up with with liquids uh diet sodas i get criticized for drinking but i'm going to continue to have those but then you know i power through the day i definitely don't feel tired i don't have a lag anymore but give also give it at least two weeks because you there's a habit as well having something in your mouth chewing feeling that fullness you can break that habit and within two three weeks you'll have done it absolutely so i'm not actually even that strict about it you said that soda uh yeah people are very kind of weirdly strict about fasting the rules and the fasting like for example i i drank uh element electrolytes when i was fasting and that has like five calories and so technically it's uh not fasting or people will say like if you drink coffee there's caffeine and they'll say that's technically not fasting because there's some kind of biological effects of caffeine whatever of course there's like biological benefits that you can argue about but there's also just experiential benefits just calorie restriction broadly has a certain experience to it that like for me personally just as you said has made me feel really good that said like especially uh i've gained quite a bit of weight uh like maybe even like 15 pounds something like that since i moved to austin texas and i i still keep the same diet but i eat a lot of meat in that one just because it's delicious because it's also the the the amazing people i met in texas it's just there's like a camaraderie a friendship of love to the people that like makes you really enjoy the uh the atmosphere of eating the brisket and the meat is this joe rogan insisting joe is i mean he's very different uh joe loves bread and pasta like he knows that his body feels best doing keto or carnivore so that's what he usually tries to stick to but he also does not hold back and he'll just eat pasta when he does pasta and he sort of enjoys life in that way i can't i don't know how to enjoy life in that way i also love pasta but i'm just not going to enjoy it because i know i i know my body ultimately does not feel good with pasta so it's a funny kind of dichotomies i i would like to uh cheat i guess by eating more meat than i you know like overeating uh on the things that i know my body feels good on as opposed to eating stuff i shouldn't like cake and all those kinds of things i tend to um i tend to find happiness in overeating the good stuff versus eating the bad stuff and the that's the kind of balance him he's like fuck it every once in a while you got to enjoy it and and then also coupled with that for him uh is just exercise like then faces demons the next day and just like burn a huge amount of calories which is i mean whatever whatever is up with that guy's mind there's an there's a ability to fully experience life which is represented by the pasta and the ability to just like fight the demons which is represented by all the crazy kettlebells and and running the hills and all this kind of stuff that he does that takes a lot out of you doing that kind of insane exercise and i think i'm more like you at least towards your direction is like i really hate exercise so i do it but i really hate it and so it's a balance that you have to strike is there something you could say about the diet side of that for you personally but in general in order to achieve calorie restriction like for me eating i know it may not sound healthy but eating carnivore eating mostly meat has been has made me feel really good both mentally and physically is there something you could say about the kinds of diets that may improve longevity but also enable calorie restriction well sure i mean the first thing that's important to know is that while many people are interested slash obsessed with what they eat the data that's come out of animal studies at least is it's far more important when you eat than what you eat and this was a fantastic study a few years ago by my friend rafael de cabo at the national institutes of health in bethesda and he had 10 000 mice on different diets hoping to find the perfect mix of carbs protein and fat and it turns out that the only ones that lived longer were the ones that only ate once a day and so that if we're we're not mice but i think that we're close enough to mice that this tells us a lot but okay but i still think the best bang for the longevity buck is to do both well eat less often and eat the right things now i'll preface this to say i'm not a nut about this i will eat occasional very occasionally a dessert usually i steal from others which doesn't count right exactly but you've got to live life right what's what's a long life if it's not enjoyable anyway but what i've i also found and this is i'll get to your question a second but my microbiome right now and stomach is at a point where if i try to overeat on a steak which i did a couple of days ago i actually had a chicken uh a fried chicken specifically for two days i felt terrible i couldn't sleep it wouldn't go down so i'm now at a point where even if i want to binge on meat and fried foods i just can't it just feels bad but what what do i recommend well what the data says which i try to follow is that plant-based foods will will be better than meat-based foods and i know that there are a lot of people disagree but one of the facts is there's a few facts one is that people who live a long time tend to eat those type of diets mediterranean okinawa diet they're eating mostly plants with a little bit of meat and not a lot of red meat and the other fact is that in animals we know that there's a there's a mechanism that's called mtor little m capital tr that responds to certain amino acids that are found in more abundance in meat and when it responds it actually shortens lifespan and the converse if you starve it of those three amino acids uh in mostly in meat then it extends lifespan and there there's a drug called rapamycin which some people are experimenting with that does that so you might be able to you know i'm just saying this here from my colleagues we don't know the results here but you could potentially take a rapamycin-like drug and counteract the effects of meat on in the long run don't know we should try that actually we could do that in the lab but uh getting to the bottom of this what i think is going on is that just like testosterone and growth hormone you will get temporary maybe not temporary um immediate health benefits you'll feel great you'll get more muscle energy but the problem is i think it's at the expense of long-term health and longevity well this is actually something i worry about in terms of long-term effects or the the cost in terms of longevity it's very difficult to know how your choices affect your longevity because the impact is down the line like just because something makes me feel good now like eating only meat makes me feel good now i wonder what are the costs down the line well think about what i i was saying about the trade-offs between growth and reproduction which is what a mouse does and a whale that grows slowly reproduces slowly lives a long time it's called the disposable soma theory um kirk would just uh propose that in the 70s what meat probably does is put you in the mouse category super fertile grow fast heal fast and then if you want to be a whale you should restrict meat uh and do things that promote the preservation of your body is it uh difficult to eat a plant-based diet that uh you perform well under so uh mentally and physically just almost i'm asking uh almost like a anecdotal question unless you know the science uh well the science is still being worked out but from the synthesis of everything i've read i try to eat a diet that's definitely full of leafy greens uh particularly spinach is great because it's got the iron that we need plenty of vitamins i also try to avoid too much fruit and berries particularly fruit juice definitely avoid that sugar high spiking your sugar is not healthy in the long run the other thing that's interesting is we discovered what are called what we call xeno hormetic molecules let me unpack that because it's terrible name and i take full responsibility with my friend conrad howitz the xeno means cross species and hormesis is the term that what doesn't kill you makes you live longer and and and be healthier and so we're getting cross species health improvements by molecules that plants make and plants make these molecules when they're also under adversity or perceived adversity for instance uh i understand if you want really healthy or good oranges you can drive nails into the the bark of the tree before you harvest same with wine you typically want them to be dry before you harvest or covered in fungus and that's because these plants make these colorful and xenohemetic molecules that make themselves stress resistant turn on their sirtuin defenses the sir genes remember and when we eat them we get those same benefits that's the idea and we've evolved to do so this isn't a coincidence it's my theory our theory that we want to know when our food supplies is under adversity because we need to get ready for a famine and so we hunker down and preserve our body and by eating these colored foods so practically speaking if it's full of color or if there's been some chewing by a caterpillar caterpillar organic grown locally in local farms i'll eat that versus a watery insipid uh light-colored um lettuce that's been grown in california so you want vegetables that have suffered you want the david goggins as the vegetables that's the xenochromatic molecules i love that tone i'm gonna take that one with me thank you yeah oh i follow him on instagram is always screaming so you want the that he's basically uh the the the xeno-harmonic version of a human um i like it so these are the molecules that are representative of the stress that's been um that a plant has been under yeah the best example of that is resveratrol which many people including myself take as a supplement grapes or grape vines produce that in abundance when they're dried out or they have too much light or fungus and that we've shown activates the so2 enzyme in our bodies which remember is what extends lifespan in yeast and slows down aging in the brain that's beautiful yeah i tend to avoid fruit as well so green veggies anything that's not very sweet so i would just say you're relatively low like you try to avoid sugary things as well yeah i'm fairly militant about that um i rarely would add sugar to anything occasionally i would um eat a slice of cheesecake but that would be you know maybe once or twice a year you have to give in occasionally but yeah anything that's sweet i would rather substitute something like stevia if i need a sugar hit what about exercise your favorite topic is there uh is there anybody talking about it yeah okay great is there benefits to longevity from exercise well no doubt that's that's proven um just like fasting it's pretty clear that that works uh for example there are studies of cyclists it was something like people that cycle over 80 miles a week have a 40 reduction in a variety of diseases certainly heart disease so that that's not even a question but what's interesting is that we're learning that you don't need much to have a big benefit it's an asymptotic curve and in fact if you overdo it you probably have reduced benefits particularly if you start to wear out joints that kind of thing but just 10 minutes on a treadmill a few times a week getting your lose your breath get hypoxia because it's cold seems to be very beneficial for long-term health um and that's the kind of exercise that i like to do aerobic though i do enjoy uh lifting weights so that is what i call my exercise which has other benefits including maintaining hormone levels male hormone levels but also really why i do it is i want to be able to counteract the effects of sitting for most of the day yeah and as you get older you lose muscle mass it's a percent or so a year and i don't want to be frail when i'm older and fall over and break my hip which is which happens every 20 seconds in this country so maintaining that strength but also doing the cardio for the longevity for the avoiding the heart disease yeah i definitely just like with fasting have the philosophical benefit of running long and running slow i enjoy because it kind of clears the mind and allows you to think and actually listen to brown noise as i run it really helps remove myself from the world and just like zoom in on particular thoughts what is brown noise it's like white noise but deeper so like the white noise is like shh and then brown noise is more like like ocean that sounds great i might try that yeah yeah it's a small sweet thing probably i'm not sure there could be signs to this i need to look this up i've been meaning to but i've when i started uh this is maybe like five years ago i started listening brown noise when i work and uh the first time i listened to it something happened to my mind where it just went like zoomed in to like in a way that it felt like really weird like how how precisely was able to sort of remove the distractions of the world and really help my mind obviously like the mind is trying to focus and then it just enabled that process of trying to focus on a particular problem i don't know if this is generalizable to others people should definitely try it if you're listening to this maybe it's just my own mind but it's funny like it made me brown noise made me realize that there's probably hacks out there that work for me that i should be constantly looking for it's almost like um an encouraging and motivating of event that maybe there's other stuff out there maybe there's other brown noise like things out there that truly like almost immediately make me feel better i don't know if it's generalizable to others but it does seem that it's the case that there's probably for many others things like that that could be discovered and so it's always disappointing when i find things in life that i wish i had found earlier like i got lasik eye surgery a few years ago and the first thought i had like the next day when i woke up is like damn it why didn't i do this way earlier there's other stuff of that nature that um they're yet to be discovered so it pays to explore yeah though you have a different mind you have quite a beautiful mind so i suspect brown noise helps you focus and because you're probably all over the place if you don't control it yeah exactly i mean it's something about it it's a programmer thing i don't the programming is a really difficult um mental journey because you have to keep a lot of things in mind you have to uh so you're constantly designing things and you have to be extremely precise by making those things concrete in code you also have to look stuff up on the internet to sort of feed like information and looking up stuff on the internet internet is full of like distracting things so you have to be really focused in the way you look stuff up in pulling that information in so it requires a certain discipline and a certain focus that uh i've been very much exploring how to do like i do it really well in the morning coffee is involved all those kinds of things you're trying to optimize uh keeping very positive inspired no social media all those kinds of things and trying to optimize for and everybody has their own kind of little journey that they try to understand you get this from like writers when you read about the habits of writers like the habits they do in the morning they usually write like two three four hours a day and that's it it's like they optimize that ritual and then there's always hunters thompson so uh sometimes it pays off to be wild what about the sleep how important is sleep for longevity i would guess based on the evidence that it's really important and because we don't know for sure but what we know from animal studies is the following if you restrict sleep from a rat for just two weeks it'll develop type 2 diabetes it's that important so that's the main thing what we also know is at the molecular level that if you disrupt your sleep wake cycle so we actually have proteins that go up and down that control our sleep wake all of us most of our cells do that if you disrupt that you'll get premature aging and guess what the opposite is true that as you get older that cycle the the amplitude becomes diminished and this is why it's harder to get to sleep as you get older and then you've got all sorts of problems and i think what's going on is this positive feedback loop which is is a disaster in your old age which is um right you're aging you can't at this moment totally prevent that and then it's disrupting your sleep then you get not enough sleep and then that's going to accelerate your aging process um and so it's known that that people who are shift workers are more susceptible to certain age-related diseases so your bottom line you definitely want to work on that it's one of the reasons i have this ring on my finger which helps me optimize my sleep and learn what i do the day before if it was a bad idea and i'll stop doing that like eating a fried chicken i see you're still carrying the burdens of that decision but is yeah you know sleep is one of those things that's making me wonder about the variability between humans a little bit and how science is often focused on like it's not often focused on high performers in a particular way and it's looking at the aggregate versus the individual cases for example like for me i don't know what the exact hours are but like power naps are incredible i tend to look at the metric of stress and happiness and joy and try to optimize those so decreasing stress increasing happiness and using sleep as just one of the tools to do that because like hitting the five six seven eight nine hour mark or whatever the correct mark is i find that to be stress inducing for me versus stress relieving like thinking about that i i feel best if i sleep sometimes for eight hours sometimes for four hours and then power nap and as long as i have a stupid private usually smile on my face that's when i'm doing good as opposed to getting a perfect amount of sleep according to whatever the latest blog post is and i also pull all-nighters still i also think there's something about the body like as long as you do it regularly it's not as stress-inducing like you know what you know what it is the reason i pull all-nighters isn't for like i'm playing diablo 3 or something is because i'm doing something i'm truly passionate about well i can also love video games but i'm doing something i'm truly passionate about and it's almost like there's the jocko willing feeling of when i'm up at seven a.m and i haven't slept all night and still i'm working on it there's a kind of a celebration of the human spirit that i really enjoy it like uh and that's happiness and to sort of then and i usually don't tell that kind of stuff to people because their first statement will be like you should get more sleep it's like no i'm doing stuff i love you should get more love in your life bro that's right so but that said in aggregate when you look at the full span of life it's probably you should be getting a consistent amount of sleep and it seems like it's in that seven eight hour range yeah but it's similar to food it it's the quality not the quantity right and and when you get it so i i look at my my data pretty often and what makes a difference to me is not the amount of hours but the quality the depth and the deep sleep is what what'll do it so if i have a lot of alcohol before going to sleep and i can see my heart rate being different but what really kills me is that i don't get a lot of that deep sleep and i wake up you know barely remembering stuff so that like you say if you're happy and contented and you're not don't have these cortisol chemicals going through your body you will more naturally get into that deep state and even if you just get four hours way better than eight hours of none of that yeah yeah that's beautiful and some of that could be genetic for me i just i just fall asleep like this if you want me to fall asleep right now i can do it it's it's no um i have no problem with the combined with coffee i just had two energy drinks i could probably uh sleep so that i don't know if that's genetics or it's kind of um i don't know what it is or maybe that i don't have kids that i'm single so i don't have uh i'm almost listening to some kind of biological signal versus societal signal on when i'm supposed to go to sleep so i just go to sleep whenever i feel like going to sleep well that's because you're self-employed so most people don't have that luxury but we're lucky the two of us that we can make our own hours yeah um but yeah it's super important and those people who have the shift work i mean they they really need to to change the way that works because they're literally killing those people is there something you can say about the the mind and stress uh in terms of effect on longevity sort of um because i don't know if you think about it this way but when you talk about the biological machine it's always these mechanisms that don't are not necessarily directly connected to the brain or the operation of the brain like what's the role about stress and happiness and uh yeah the sort of higher cognitive things going on in the brain on longevity right well that's a great point that the brain is is the center for longevity actually we we do know that first start when when i'm stressed i can see mentally stressed then i can see it in my body heart rate hormones it's clear you know that's no true surprise so you've got to work on your brain first and foremost if you are totally freaked out agitated uh all the time you will live shorter i'm certain of it you know i keep fish i'm a big aquarium guy and you can see the difference between the the fish that's having a good time and dominant and one that gets picked on yeah it just looks like crap you don't want to be that the little fish getting picked on if you can help it so i used to be extremely stressed as a kid i was a perfectionist very shy always worried about being a failure if i didn't get an a plus you know i was crying in my bedroom that kind of sad existence i got into my 20s then in my 30s and realized that's not the way to live so i've worked very hard to get to this point where i almost never get stressed never there's nothing that i've never gotten angry in my lab i've got 20 kids sometimes it's like a most of the time it's like a kindergarten um i haven't lost my temper i very calm but that's intentional um and i don't worry about stuff millions of dollars billions of dollars at stake sometimes keep it cool it's only life we're all headed to the same place anyway don't worry about it um but the the to answer your question i think in a better way if you manipulate the brain of an animal i'll give you an example if we turn on this cert gene that i mentioned sir one we a good friend of mine that wash you shiny my did this they upregulate the operate of that gene just in the neurons of the animal it lived longer so that's sufficient to extend lifespan we also know that you can manipulate the part of the brain called the hypothalamus which leaches a lot of chemicals into the body and proteins most of which we don't know yet but just changing the inflammation of that little organ or part of the brain is sufficient to make animals live longer as well so get your brain in order first before you tackle anything else i would say so you kind of mention this with the inside tracker there's a ability to take blood measurement and then infer from that a bunch of different things about your body how you can improve how you can improve the longevity and you've also mentioned saliva and more efficient ways to uh to get data uh what does that involve what's the future of data collection look like yeah for the human biological system right well yeah the the issue with with blood is you need someone to take it it's it i mean or you prick your finger which hurts yes so you gotta have something better so i think what the future looks like is that you'll spit onto a little piece of paper and stick it in a machine and it'll it'll do that for you but we're not there yet so the intermediate um future that that i'm building right now is that you would take a swab of the inside of your mouth which is the easiest way to take cells out of your body and just ship them off okay so called a buckle swab um i think we we became very used to that right right now because of covert people don't like going to the doctor as much they don't like going out they just want to have home tests and so that i think is the next 10 years where you'll get a kit in the mail you'll swab your cheek stick it back in an envelope send it off and you know a week later you have either a doctor's report or a health recommendation and what can you get off a cheek swab well you can get anything you can get hormones stress levels stress hormones blood glucose levels you can also tell your age reasonably accurately doing that actually quite accurately and those clocks cannot just tell you how you're doing over time but can be used to give you recommendations to slow that process down because some people sometimes are 10 years older biologically than their actual chronic chronological age i mean why does it matter how many times the earth's gone around the sun seriously who cares about birthdays it's how long your body's clock has been ticking and how fast so i could take a cheek swab from you today lex take it back to my lab and we then by tomorrow tell you how old you are biologically based on what we call the epigenetic clock and you might be freaked out you might be happy but either way we can advise you on how to improve the trajectory because we know that smoking increases the speed of that clock we also know that fasting and people who eat the right foods have a slower clock without that knowledge you're flying blind but i like the idea of a swab because it's it's just so easy we've a lot of us have done something like that for covert tests it's not even i've been doing a non-stop a rapid antigen test so let me say that particular one rapid antigen test they've been a source of frustration for me because like everybody should be doing it it's so easy we've also been working in my lab on democratizing these tests to bring them down from a few hundred bucks to a dollar so just to clarify you're talking about not research you talk about like company stuff like actual facing things i i well right the research on bringing the price down has occurred in my lab at harvard and then that intellectual property is being licensed and has been licensed out to a company yeah that that will be uh consumer-facing so anybody for a small amount of money can do this well you got subscriber number one obsessed i think that's a beautiful beautiful idea so somebody who maybe i would have been more hesitant about it until a covid uh but home tests are super easy i almost wanted to share that data with the world like in some way not not the entirety of the data but like some visualization of like how i'm doing like it's almost like uh like you know when you share if you had like a long run or something like that i wish i could share because it inspires others and then you can have a conversation about like well what are the hacks that you've tried and have a conversation about like how to improve lifestyle and those kinds of things that's grounded in data that's exactly that's what's that's what's going to happen now everything's anonymous of course we talked about security there but once it's anonymized you can then plot these numbers and i've plotted my epigenetic age versus hundreds of other people who have taken this test now and i can tell you where i fit relative to others in terms of my biological age and i'm happy to share that with you all because it's pretty low you can choose to share it of course not everyone wants to share that but when you go to the doctor first of all your doctor doesn't does treat you as though you're an average person and none of us are average there's no such thing but second of all we never know how we're doing relative to others because we all most of us we we don't share our information so we might have this number and that number but do you know that your numbers are good for your age or not you have no idea no even your doctor probably doesn't even know so this this graph that i'm talking about is the beginning of a world where you can say how am i doing i'm a you know for the two of us we're white and we're male and we're this age and we do this are we good are we doing the right things or the wrong things do we need to fix certain things and this is what the future is it's forget about just experimenting and not knowing the result i mean who doesn't experiment and doesn't look at the data no one it makes no sense so we're going to enter a world where we have a dashboard in our body the swabs the blood tests the biosensors where our doctors can look at that but we can also look at it and they can recommend you know go to this restaurant down the road they've got this great meal it's high in whatever you need today because you're lacking vitamin d and vitamin k2 go for it ridiculous question or perhaps not if you look maybe 50 years from now or 100 years from now a person born then what do you think is a good goal in terms of how long a person would live like what is the maximum longevity that we can achieve through the methods that we have today of uh or are developing some of the things we've been talking about and in terms of genetics in terms of biology what's is there a number right uh well so it changes all the time because technology's changing so quickly i keep revising the number upward uh but i would say that if you do the right things during your life and start at an early age let's say 25 we don't want malnutrition starvation that's not what i'm talking about but in your 20s start eating the kind of diets that i talked about skipping meals in animals that gives you an extra 20 to 30 percent we don't know if that's true for humans and that would you know even five percent more would be a good a big deal for the planet i think that we should all aim to at least reach a century um i i'm i'm a little bit behind i was born too early to benefit the most from all of this discovery those of you who are in your twenties you should definitely aim to reach a hundred i don't see why not consider this is really important the average life span of a human that looks after themselves and but doesn't pay attention is about 80 okay japan that's the average age for a male bit higher if you do the right things in your life which is eat healthy food don't overeat don't become obese do a bit of exercise get good sleep and don't stress that gives you on average 14 extra years that gets you to 94. so getting to 100 if you just focus on what i'm talking about it's not a big deal so what's the maximum well we know that one human made it to 122 and a number of them make it into their teens i think that's also the next level of of uh of where we can get to with the types of technologies that i'm talking about medicines like i mentioned rapamycin there's one called metformin which is the diabetes drug which i take that in combination with these lifestyle changes should get us beyond a hundred how long can we ultimately live well there's no maximum limit to human lifespan why can a whale live 300 years but we cannot we're basically the same structure we just need to learn from them so anyone who says oh you max max out at x i think is is full of it there's nothing that i've seen that says biological organisms have to die there are trees that live for thousands of years and their biochemistry is pretty close to ours what do you think it means to live for a very long time let's say if it's 200 years we're talking about or a thousand years there's some some sense you could argue that there is immortal organisms already living on earth like there's bacteria so there's certain there's certain living organisms that in some fundamental way do not die because they keep replicating their genetic information they keep like cloning themselves is is it the same human if we can somehow persist the human mind like copy clone certain aspects and just keep replacing body parts um do you think that's another way to achieve immortality to achieve of a prolonged sort of increased longevity is to replace the parts that break easily and keep because actually from your theory of um aging as a degradation of information it's an information theory view of aging like what is what is the key information that makes a human can we persist that information and just replace the the trivial parts uh yeah i mean the short answer is yes we're already replacing body parts but what makes us human is our brain everything else is is sub-optimal except our brain the ability to replace actual neurons is really hard right i think it might be easy to upload rather than replace neurons because they're so tight it's such a network and just perturbing the system you know it's it's uh it's stretching this cat you you change everything once you get in there the problem is um well i guess the solution let me go to the solution that's more interesting what we're learning is that if you reverse the age of nerve cells they look it looks like they get their memories back right so the memories are not lost they're just that the cells don't know how to interpret them and function correctly and this is one of the things we're starting in my lab if you take an old mouse that has learned something when it was young but forgotten does it get that back and all evidence points to that being true so i'd rather go in and rejuvenate the brain as it sits rather than replace individual cells which would be really hard what do you think about like efforts like neurolink which basically you mentioned uploading are trying to figure out so creating brain computer interfaces they're trying to figure out how to communicate with the brain but one of the features that is trying to record the human brain more and more accurately do you have hope for that to um of course there's uh it will lead to us better understanding from a neuroscience perspective the human mind but do you have hope for it increasing longevity in terms of how it's used i think that it can help with certain diseases uh but i see at least within our lifetime that's the best use of it is to be able to replace parts of the body that are not functioning such as the the retina and other parts the visual cortex back here that that's going to be doable in terms of longevity maybe we could put something on the hypothalamus and start secreting those hormones and get that back ultimately i think it the best way to preserve the brain uh is going to be to uh record it but also i think it's going to require death unfortunately to then do very detailed scans even if you have enough time and money atomic microscopy and rebuild the brain from scratch rebuild from scratch yeah we are living more and more in the digital world i wonder if if the scanning is good enough for the critical things in terms of memories in terms of the particular quirks of your cognitive processes they're not they're not yeah we're not we're not close yes but we've made quite a bit of progress so it's uh if you're um if you're an exponential type of person yeah well let's dream a little here yes the way it would work that i could see it working is so you take a single cell slice through your your dead brain and we can now the problem the problem with the engineering aspect is that the engineering is the physical aspect of the brain is is not even half the problem the problem is which genes are switched on and off this experience that we're having here is is altering certain genes in neurons that will be preserved hopefully for for a number of decades but you cannot see that with a microscope easily but there are technologies invented actually just down the hall in the building i'm at george church invented away his lab invented a way to look at which genes are switched on and off not only in a single cell which any lab can do these days but in situ where it's situated in the brain so you can say okay this nerve cell had these genes switched on and they switched off we can recreate that but just scanning the brain and looking how the nerves are touching each other is not going to do it wow okay so you have to scan the full biology the full details and look at the epigenome and the apogenome too yeah which genes are on and off it's just easier to reset the epigenome and get them to work like they just use we're doing that now use the hardware already have just figure out how to uh make that hardware last longer right ultimately information will be lost even genetic information degrades slowly through mutations so we immortality is not achievable through that means though i think we could potentially reset the body hundreds of times and live for thousands of years okay so we talked about biology let's forgive me but let's talk about philosophy for just a brief moment so somebody i've enjoyed reading ernest becker wrote the denial of death there's also martin heidegger there's a bunch of philosophers who claim that most people live life in denial of death sort of we don't fully internalize the idea that we're going to die the because if we did as as they say there will be a kind of terror of um i mean a deep fear of death the fact that we don't know what's like we almost don't know what to do with non-existence with disappearing like our the way we draw meaning from life seems to be grounded in the fact that we exist and that we some point will not exist is terrifying and so we live in an illusion that we're not going to die and we run from that terror that's what ernest beckham would say do you think there's any truth to that oh i know there's truth to that i experience it every day when i talk to people we have to live that way although unfortunately i can't but for most people it's extremely stressing distressing to think about their own mortality we think about it occasionally and if we really thought about it every day we'd probably be brought to tears how much we not just miss ourselves but miss our family our friends we are all living life forms have evolved to to not want to die and when i mean one biochemically genetically physically that yeast cell the cells that i studied at mit they were fighting for their lives they didn't think but our brain has evolved the same survival aspect of course we don't want to die but the problem for us unfortunately it's a curse and a blessing is that we're now conscious we know that we're going to die most species that have ever existed don't that's a burden that's a curse and so what i think's happened is we've evolved certainly to want to live for a long time perhaps never want to die but the thought about dying is so traumatic that there is an innate part of our brains and it's probably genetically wired to not think about it i really think that's part of being human and it because you know think about tribes that obsessed with longevity every day and that were going to die they probably didn't make much technological progress because they were just crying in their hearts every day or you know on the savannah so i really think that we've evolved to naturally deny aging and it's one of the problems that i face in my career and you know when i speak publicly and on social media is that it's shocking people don't want to think about their age but i think it's getting better i think my book has helped these tests that we're developing should help people understand it's not a problem to think about your long-term health in fact if you don't you're going to reach 80 and really regret it and the other side of it so again ernest becker but also victor franklin recommended highly man search for meeting uh bernard williams he's a moral philosopher they kind of argue that this knowledge of death even if we often don't contemplate it we do at times and the very the what you call the curse which i agree with you it's a it's a curse and a blessing that we're able to contemplate our own mortality that gives meaning to life so death gives meaning to life is what viktor frankl's argues i would probably argue the same there's something about the scarcity of life and contemplating that that makes each moment that much sweeter is there something to that i think it's individual in my case it's completely wrong i appreciate you saying that i don't get joy out of every day because i think i'm going to die yeah i get joy out of every day because every day is joyous and i make it that way and even if i would if i thought i was going to live forever i would still be enjoying this moment just as much and i bet you would too well that's uh i think about that a lot i i think it's very difficult to know i'm almost afraid that i wouldn't enjoy it as much if i was immortal i'm almost afraid to want to be immortal or to live longer because it perhaps is a kind of justification for me to accept that i'm going to die is saying like oh if i was immortal i wouldn't be able to enjoy life as much as i do but it's very possible that i wouldn't enjoy just as much of course enjoying life whether you're mortal or not takes work like it it requires you to have the right kind of freedom of mind you can discover you can focus your mind on the ugliness of life there's plenty of ugly things in this world and you can focus on them you can complain whenever like you know if it's raining outside you can you can focus on the fact that you have shelter and you enjoy the the hell out of it or you can enjoy running in the rain when it's warm and like the the beauty of nature just being one with nature or you can just complain this fucking weather again in boston and there you see they're always raining or freezing damn it and like uh the the same the same thing with like wi-fi going out on airplanes like you can either complain about like stupid wi-fi and on jetblue or something or you could say like how incredible it is that i can fly through the sky and in a matter of hours be anywhere else in the world and then it could also on occasion watch uh like check email and even watch movies through this while connecting through satellites that are flying to space so it's a matter of perspective and perhaps there's an extra level of work required when you're immortal because it's easier when you're immortal or live longer to uh to be lazy to delay stuff but if you're not you can still derive the same amount of joy it's possible it's possible it's definitely possible in my life i i went from being the nothing's working to every day is great to wake up to and i i think even if you live i think you're gonna live forever you can you can enjoy every day what i do is everything's relative we can compare ourselves to our neighbor who has more money or to the flight that should have had wi-fi or which is what i do i'm still six years old remember what a six-year-old does says look i can when i tell my fingers to form a fist they actually do that that's really cool that's how i live my life you know i'm i can pick up on your desk here this metal object it's a metal cube about an inch by an inch by an inch and i i tell myself not not about cubes but about inanimate objects probably once a day i'll say i'm a living thing i can think i can move i can eat i am full of energy and there's that leaf or this cube here that will never be alive that's what i look at and compare myself to and for as long as i live if it's forever of course it won't be but even if it was forever the relative to this lump of metal on this table here we are wondrous things in the universe and probably the most wondrous things in the universe yeah we're able to deeply appreciate the leaf or the cube and deeply appreciate ourselves which is uh it can be a curse but it's mostly a gift especially when you're such a beautiful poem now i'm six i'm as clever as clever so i think i'll be six now forever and ever that's a good thing to aspire to your uh your grandmother was on to something david this is uh incredible conversation i'm a huge fan of your work so thank you for wasting your valuable time with me today i really really appreciate it this was awesome thank you for having me on lex appreciate it thanks for listening to this conversation with david sinclair and thank you to on it clear national instruments simply safe and linode check them out in the description to support this podcast and now let me leave you some words from arthur shorpenhauer all truth passes through three stages first it is ridiculed second it is violently opposed third it is accepted as being self-evident thank you for listening and hope to see you next time you