2021-06-07 - Interview Dr. David Sinclair - Lex Fridman Podcast - Extending the Human Lifespan Beyond 100 Years
- Length: 1:41:33
- Interviewee: Dr. David Sinclair
Transcript
Introduction
| 0:00 | the following is a conversation with david sinclair he is a professor in the department of genetics at harvard |
| 0:06 | and co-director of the paul f glenn center for the biology of aging at harvard medical school he's the |
| 0:12 | author of the book lifespan and co-founder of several biotech companies he works on |
| 0:18 | turning age into an engineering problem and solving it driven by a vision of a world where |
| 0:24 | billions of people can live much longer and much healthier lives quick mention of our sponsors |
| 0:30 | on it clear national instruments and i simply safe and lino'd |
| 0:36 | check them out in the description to support this podcast as a side note let me say that longevity |
| 0:41 | research challenges us to think how science and engineering will change society |
| 0:47 | imagine if you can live a hundred thousand years even under controlled conditions like in a spaceship say |
| 0:53 | then suddenly a trip to alpha centauri that is uh 4.37 light years away |
| 0:58 | takes a single human lifespan and on the psychological maybe even philosophical level as the horizons of |
| 1:06 | death drifts farther into the distance how will our search for meaning change does meaning require |
| 1:12 | death or does it merely require struggle reprogramming our biology will require |
| 1:18 | us to delve deeper into understanding the human mind and the robot mind |
| 1:23 | both of these efforts are as exciting of a journey as i can imagine this is the lex friedman podcast and |
| 1:30 | here is my conversation with david sinclair i usually feel like the |
Staying young at heart
| 1:35 | same person when i was 12 like when i right now as i think about myself i feel |
| 1:42 | like exactly the same person that i was when i was 12 and yet |
| 1:48 | um i am getting older both body and mind and still feel like time hasn't passed |
| 1:53 | at all do you um feel this tension in yourself that you're the same person |
| 1:59 | and yet you're aging yeah i have this tension that that i'm still a kid but that helps in my career |
| 2:05 | scientists need to have a wonder about the world and you don't want to grow up 12 year olds and even younger |
| 2:11 | 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 |
| 2:17 | think that i can see things for the first time if i choose to and then explain them as i would to a 60 |
| 2:22 | 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 |
| 2:29 | got a book i've got uh you know science to do companies to run and so i have to |
| 2:34 | and on most days just pretend to be a grown up and and be mature but i definitely don't feel that way |
| 2:40 | there's uh there's something i really appreciated in opening your book you talked about your grandmother |
| 2:46 | and on this kind of theme on this kind of topic uh she first of all had a big influence |
| 2:53 | on you my grandma mother had a big influence on me he also mentioned this poem by the |
| 3:00 | author of winnie the pooh allen alexander milne maybe i can |
| 3:05 | read it real quick because i on the topic of being children when i was one i had just begun when i |
| 3:12 | was two i was nearly new when i was three i was hardly me when i was four i was not much more when |
| 3:19 | i was five i was just alive but now i am six i am as clever as clever so i think i'll |
| 3:26 | be six now forever and ever um so this idea of |
| 3:34 | being six and staying six forever being youthful being curious being |
| 3:39 | childlike this and other things what uh |
| 3:44 | influence has your grandmother had in your thinking about life about death about uh love |
| 3:53 | 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 |
| 3:59 | grandmother who partially raised me and she was as much a bohemian as an |
| 4:04 | artist philosopher and she's one of those people that wouldn't talk about the little things |
| 4:09 | she said i hate small talk don't talk to me about politics or the weather yeah talk to me about |
| 4:15 | human beings and culture so i was raised on that and this poem was one that she read to me |
| 4:20 | often because she knew that the mind of a child is precious |
| 4:26 | it's honest uh it's pure and she grew up during the second world war and in |
| 4:32 | hungary and budapest witnessed the worst of humanity she was trying to save a whole group of jewish friends in her |
| 4:40 | apartment saw what happened after the world war which was um there was the the russians were in |
| 4:47 | control and locals weren't necessarily treated well if they were rebellious which she was |
| 4:52 | 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 |
| 4:58 | when humans do their worst and her words to me expressed in part through that poem was |
| 5:05 | david always stay young and innocent and have wonder about the world |
| 5:11 | and then do your best to make humanity the best it can be and that's who i am that's what i live |
| 5:18 | 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 |
| 5:23 | whether it's aliens or some future human historian that we can do better than we did in the 20th century |
Bringing people back to life
| 5:31 | you know we mentioned offline this idea of bringing people back to life through um through artificial |
| 5:36 | intelligence sort of i don't know if you've seen videos of basically animating people back to life |
| 5:45 | meaning uh whether it's for me personally i've been working on specifically about albert einstein |
| 5:51 | but also alan turing isaac newton and richard feynman |
| 5:56 | and it's it's an opportunity to bring people that meant a lot to others in the world and uh |
| 6:04 | animate them and be able to have a conversation with them at first to try to visually |
| 6:12 | visually explore the the full richness of character that they had |
| 6:17 | as they struggle with the ideas of the modern age sort of it's less about bringing back their mind and more |
| 6:24 | bringing back the the visual quirks that made them who they are and then maybe in the future it's using |
| 6:31 | the textual the visual the the the video the audio data to actually |
| 6:37 | compress down the person for who they are and be able to generate text there's a few |
| 6:42 | companies there's replica which is a chat engine that was born out of the idea of bringing |
| 6:48 | the the founder uh lost her friend uh to uh he he got ran over by a car |
| 6:55 | and the initial reason she founded the company was trying to just have a conversation with |
| 7:02 | her friend she trained a machine learning uh natural language system |
| 7:07 | 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 |
| 7:14 | very the the conversation was very trivial it was obvious that it's uh you know a ai agent but it |
| 7:21 | gave her solace it made her actually feel really good and that's the way i wonder if it's |
| 7:27 | possible to bring back people that are that means something to us personally not just einstein but |
| 7:34 | people that we've lost and in that way achieve a kind of small artificial |
| 7:41 | immortality i don't know if you think about this kind of stuff uh well i'd definitely think about a lot of things |
| 7:46 | that that one's a really good one there's a great black mirror episode about the the wife who brings back the |
| 7:51 | 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 |
| 7:58 | 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 |
| 8:06 | early though it may hold you back from moving on that's another thing that could happen as a negative |
| 8:11 | but i think that's great and i also think that it's going to be possible especially when we're recording some of |
| 8:16 | us every aspect of our lives whether it's our face or uh things we see right |
| 8:22 | eventually one day everything we see can be recorded and then you can you can build somebody's experience and |
| 8:29 | and thoughts uh speech and and you will have replicas of everybody |
| 8:34 | um at least digitally and physically you could do that too one day but that that's a good idea especially |
| 8:40 | 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 |
| 8:45 | is benjamin franklin really well i wouldn't go back in time um i would but i'd prefer to bring him |
| 8:52 | into the future and say can you believe we have this thinking machine in our pockets now |
| 8:58 | and he just see the look on his face as to where humanity has come because i think of him as a modern guy |
| 9:03 | that just was before his time yeah so you're you're thinking benjamin franklin the scientist |
| 9:08 | not benjamin flanken the political thing because he'd be very upset with congress right now right so maybe talk to him about science |
| 9:15 | and technology not uh not politics or maybe just don't get him on twitter because he'll be very |
| 9:20 | upset with human civilization you know i wonder what their personalities are like isaac newton it does seem complicated to |
| 9:28 | figure out what their personality is like even friedrich nietzsche who i also thought about feynman is |
| 9:34 | we just have enough video where we get the full kind of um i mean it shows you |
| 9:41 | how important it is to get not the official kind of book level presentation of a |
| 9:47 | human but the authentic the full spectrum of humanity you mentioned collecting data |
| 9:53 | about a person collecting the whole thing the whole of life the ups and downs the embarrassing stuff the |
| 9:59 | beautiful stuff not just the things that's condensed into a book and then with finding you start to see that a little bit |
| 10:05 | through conversations you start to see peaks of like that genius and then through stories about him from |
| 10:12 | others and then certainly you uh the sad thing about alan turing for example |
| 10:17 | is there's very little if any uh recording of him in fact i haven't |
| 10:22 | been able to find recording allegedly there's supposed to be a recording of him doing some kind of radio broadcast but i |
| 10:29 | 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 |
| 10:36 | realize how the upside how nice it is to collect |
| 10:41 | data about a person uh to capture that person there's that's the upside of the |
| 10:47 | modern internet age the digital age that that information uh yeah creates a kind of immortality |
| 10:55 | 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 |
| 11:02 | they're gone so that's a really interesting opportunity you um you've also mentioned to me offline |
Wearables and tracking health data
| 11:07 | that you're really excited about all the different wearables and all the different ways we can collect |
| 11:13 | information about our bodies about uh well the whole thing is what's most |
| 11:19 | exciting to you in terms of collecting the the biological uh data about a human being |
| 11:27 | well so i'm a biologist i find animals and humans as machines very interesting it's one of |
| 11:34 | the reasons i didn't become an engineer or a surgeon i wanted to understand how we actually are built |
| 11:40 | and so i think a lot about machines merging with humans and the first of |
| 11:47 | that are the bio wearables and so i talked a lot about this i wrote about it um in life span the book and |
| 11:53 | pictured a future where you would be monitored constantly so that you wouldn't suddenly have a |
| 11:58 | 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 |
| 12:04 | you need an antibiotic or not um long term how old are you how to fix |
| 12:09 | things what should you eat what should you take what should you do these devices i predicted would be |
| 12:15 | smarter better educated than you than your physician and would augment them and then there'd be a human that would |
| 12:20 | just tick off to see if that it's correct and they approve i also was predicting in the book that |
| 12:27 | we would have video conferences with our doctors and that medicines would be delivered initially by courier but eventually by |
| 12:33 | drones and get it to you sometimes in an emergency and that we could even have pills that were synthesized or delivered |
| 12:40 | um in your kitchen and combined certainly what's amazing about that is that what |
| 12:46 | are we now two years since the book came out even less and that future is basically here |
| 12:51 | already covered uh 19 accelerates accelerated that incredibly |
| 12:56 | 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 |
| 13:03 | before it forms a tumor you can of course do your genome very cheaply for less than a hundred dollars now |
| 13:10 | there are bio wearables already i wear this ring from aura that i have number of years of data i've |
| 13:17 | 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 |
| 13:23 | data as well and there's 34 different parameters on my testosterone my blood glucose my |
| 13:28 | inflammation and i use all that data to of course i wear a watch that that |
| 13:33 | measure things as well i use that data to keep my body in optimal shape so i'm |
| 13:39 | now 51 and according to those parameters i'm at least as good as someone in their early |
| 13:44 | 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 |
| 13:52 | know now eat a little dessert once in a while so that's the future we're in right now |
| 13:58 | anyone can do what i just said but in the very near future just in the next few years |
| 14:04 | you can be wearing wearables so i'm currently wearing a little what's called a bio sticker uh this one |
| 14:12 | i just put on last night uh it's about an inch long a few millimeters yeah |
| 14:18 | people just listening it's uh san diego's chest yeah it's just the how does it attach it's just kind of |
| 14:24 | it sticks on sticks yeah so on one side you have an on button that you press the lights come on flashes four times |
| 14:29 | it's good to go it immediately syncs to your phone and this one uh the it's called a bio button |
| 14:36 | 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 |
| 14:41 | mainly for doctors to monitor patients that go home after a heart attack or surgery but that's medical grade fda approved |
| 14:47 | device so there will be a day in fact it's already here that doctors are using these to get patients |
| 14:53 | to go home and save a week in hospital two thousand dollars at least for each patient |
| 15:00 | that's massive safe um savings for the hospital but ultimately what i'm excited about is |
| 15:06 | a future that isn't that far off where everybody certainly in developed |
| 15:11 | countries eventually these will cost a few cents and rechargeable the only cost will be the software subscription that can be monitored |
| 15:17 | constantly and to give an idea what this is measuring me at a thousand times a second is my vibrations as i speak |
| 15:26 | my orientation it can already has told me this morning how i slept where i slept what side i slept on |
| 15:33 | uh we've got sneezing coughing body temperature heart rate heart of other parameters of |
| 15:40 | the heart that would indicate heart health these these data are being used to now |
| 15:47 | to predict sickness so eventually we'll have just in the next |
| 15:52 | year or so the ability to predict whether something or diagnose whether something is pneumonia |
| 15:58 | or just a rhinovirus that can be treated or not right this is really going to not just |
| 16:05 | revolutionize medicine but i think extend lives dramatically because if i have if i'm going to have a |
| 16:10 | heart attack next week and that's possible this device should know that and i'll be in hospital before i even have it |
| 16:16 | maybe you can talk a little bit about inside tracker because i saw that there's some really cool things in there |
| 16:22 | like it actually so maybe you can talk about i guess that you're collecting blood and to give it the data so |
| 16:30 | and it has like basic recommendations on how to improve your life so we're not just talking about diseases |
| 16:36 | right like anticipating having a particular disease but it's almost like guiding your trajectory to |
| 16:41 | life how to whether it's extend your your life or just live a more fulfilling like improve the |
| 16:47 | quality of life i suppose this is the right way to say it what how does inside tracker work uh |
| 16:52 | what the heck is it because i thought there was also pretty cool yeah what is it is it something other people can use |
| 16:58 | you can definitely use it uh you can sign up it's consumer it's like a company consumer facebook |
| 17:03 | company it is yes uh and i also want to democratize the |
| 17:08 | 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 |
| 17:15 | you'd go to a lab core request in the u.s it's also available overseas you can upload your own data |
| 17:21 | for a minimal cost and get the algorithms the ai in the background to take that data plot |
| 17:28 | where you are against others in your age group as in terms of health and longevity by your age they call it no |
| 17:34 | inner age but also it provides recommendations and this isn't just a bunch of bs it sounds like |
| 17:40 | it might be to say i'll go eat this or go to that restaurant and order that but it's actually based on |
| 17:46 | they basically this company has entered hundreds now it would be thousands of scientific |
| 17:51 | papers into their database and hundreds of thousands of human data points and they have |
| 17:56 | tens of thousands of individuals that have been tracked over time and anonymously that data is used to say |
| 18:02 | 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 |
| 18:09 | showed that the recommendations for food and supplements um |
| 18:15 | was better than the leading drug for type 2 diabetes that's so cool the idea that you can |
| 18:20 | connect like skipping the human having to do this work you can connect the scientific papers |
| 18:27 | almost like meta-analysis of the science connected to the individual data |
| 18:32 | and then based on that sort of connect your data to whatever the proper group is within the |
| 18:38 | whatever the scientific paper is to make the suggestion of how how like how that work |
| 18:44 | applies to your life and then that ultimately maps to like a recommendation what you should do with your life |
| 18:51 | like it all like this giant system that ultimately recommends you should drink more coffee or less |
| 18:58 | 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 |
| 19:04 | way better than we do and and our doctors as well the idea of going to a doctor once a year for an |
| 19:09 | annual checkup and having you know males get a finger up their butt and uh you know you cough that that to me is |
| 19:15 | a joke that's medieval medicine and that's very soon going to be seen as medieval |
| 19:21 | yeah it's um to me as a computer science person it's always upsetting to go to the |
| 19:28 | doctor and just look at him and like realize you know nothing about me |
| 19:33 | like you you're you're you're making your like opinions based on like it is very valuable |
| 19:40 | years of intuition building about basic symptoms but you're just like it is medieval |
| 19:45 | they're very good at it in fact doctors in medieval times are probably damn good at working with very little |
| 19:53 | but the thing is i'd rather pref for a doctor that doesn't really know |
| 19:59 | what they're doing but has a huge amount of data to work with well you're right and many of my good |
| 20:04 | friends are doctors i work at hard so i'm not against the profession at all yeah but i think that |
| 20:10 | 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 |
| 20:16 | would doctors do the same if we could we step back to the big profound philosophical |
How to solve aging
| 20:22 | both tragic and beautiful question about age how and why do we age is it uh |
| 20:30 | from an engineering perspective he said you like the biological machine is that a feature or a bug of the |
| 20:35 | biological machine it is both a bug and a feature uh evolutionary speaking we |
| 20:43 | only live as long as we need to to replace ourselves efficiently if you're a mouse you're only going to |
| 20:48 | 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 |
| 20:56 | of their resources to reproducing rapidly but they don't put a lot of energy into preserving their soma which |
| 21:02 | is their body conversely a baleen type of whale a bowhead whale in particular will live |
| 21:08 | 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 |
| 21:14 | that lasts we're somewhere in between because we've you know we've really only just come out of the savannas where we |
| 21:19 | could be picked off by a cat we were pretty wimpy going back six million years ago |
| 21:25 | uh so we we actually need to evolve quicker than evolution will and that's |
| 21:30 | why we can use our oversized brains and intuition to give us what evolution |
| 21:36 | 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 |
| 21:42 | 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 |
| 21:48 | need to engineer ourselves to be healthier and longer lived so getting to aging we we can do better |
| 21:55 | right whales do way better we're trying to learn how whales do that and if you ask really anybody in the |
| 22:02 | field now professor they'll say there are eight or nine hallmarks of aging which are really it's |
| 22:08 | a it's a word for causes of aging so that you probably have heard of some of these your |
| 22:13 | listeners will have a loss of telomeres the ends of the chromosomes like their little |
| 22:19 | ends of um shoelaces that kind of thing they get too short cells stop dividing becomes senescent |
| 22:24 | they they become they put out what are called mitogens that cause cancer and inflamma inflammatory molecules that's |
| 22:31 | another aspect of aging cellular senescence another one is loss of the energetic so mitochondria the |
| 22:36 | battery packs wind down there's a whole bunch stem cells |
| 22:41 | proteostasis well these are our achilles heels that i'm talking about that are common amongst all life forms |
| 22:47 | really but if you wanted me to jump to the chase as to where what is the upstream defining factor if |
| 22:54 | we boil it down what do we get so most biologists would say you can't boil it down |
| 22:59 | it's too complex i would say you can boil it down to an equation which is the preservation of information |
| 23:05 | and lost due to entropy i.e noise and that is the basis of my research |
| 23:12 | it originally came out of discoveries in yeast cells where i went to mit in the 1990s you studied |
| 23:17 | bread i kind of did i studied the uh the makers of bread a little yeast called |
| 23:24 | saccharomyces cerevisiae which at the time was one of the hottest excuse the pun uh organisms to work on yes |
| 23:30 | but they we we figured out in the lab why yeast cells get old and found genes that control that |
| 23:36 | process and made them live longer which was an amazing four years of my life |
| 23:42 | one of those genes had a name with an acronym sir2 now the two is irrelevant |
| 23:49 | the s-i-r is important and the most important letter out of all of those three is i which stands for information silent |
| 23:57 | information regulator number two when you put more copies of that gene in just put in one more copy |
| 24:02 | the yeast cells lived 30 longer and suppressed the cause of aging which was the dysregulation of information in the |
| 24:08 | cell and then so fast forward to now i've been looking in humans and mice because they live |
| 24:15 | shorter and cheaper to study where the loss of information in our bodies is a root cause of aging |
| 24:22 | and i think it is your boldness in viewing biology in this way is |
| 24:28 | fascinating because that also leads to a kind of |
| 24:34 | uh it's almost like allows for a theory of aging like like you could boil it |
| 24:41 | down to a single equation and it leads to a perhaps a metric that allows you to optimize |
| 24:47 | aging sort of in the fight against entropy to figure out which mechanisms like you |
| 24:53 | said the the silent information regulator which mechanisms allow you to preserve information |
| 24:58 | now without like without injecting noise without without creating entropy without |
| 25:04 | creating degradation of that information for some reason converting biology |
| 25:11 | which i thought was mostly impossible into an engineering problem feels like it makes it amenable to |
| 25:18 | optimization to solving problems to creating technology that can |
| 25:23 | whether that's genetic engineering or ai it makes it uh possible to uh |
| 25:29 | create the technology that would improve the the degradation of information and aging |
| 25:36 | is there more concrete ways you think about the kind of information we want to preserve and also is there good ideas about |
| 25:45 | regulators of that information about ways to prevent the distortion and degradation |
| 25:52 | of that information right so that we have some information regulated genes in our bodies we have seven of them |
| 25:58 | uh certain one through seven they're called and we found in in mice one way to slow down the loss of |
| 26:03 | information is to just give more of these um to up regulate these genes so we we |
| 26:09 | made a mouse that has more of this so t1 gene turned it on and that slowed down the aging of the brain |
| 26:15 | and preserved their information now what information am i talking about you might ask well again you can simplify biology |
| 26:21 | there are two types of information in the cell primarily the one we all read about and know about is the dna the |
| 26:28 | genome and that's base four information atcg the four chemicals that make up the various |
| 26:34 | sequences of the genome billions of letters and that also degrades over time but |
| 26:40 | what's been fascinating is that we find that that information is pretty much intact |
| 26:45 | in old animals and people you can clone a dog one of my friends in l.a just cloned his dog three times |
| 26:50 | so this is doable right it means that the genome can be intact but what's the other type of information |
| 26:56 | it's the epigenome the regulators of the genetic information |
| 27:01 | and physically that's really just how the dna is wrapped up or looped out for the cell to access it |
| 27:06 | and read it so it's similar to an excuse this analogy but it's a good one um a compact disc or |
| 27:13 | a dvd those pits in the foil are the digital information that's the genome |
| 27:19 | and the epigenome is the reader of that information and in in a different cell you'd read different |
| 27:24 | music different songs different symphonies and that's what gets laid down when we're |
| 27:30 | in the womb and that gives makes a skin skin cell forever a skin cell and not a brain cell tomorrow |
| 27:36 | 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 |
| 27:41 | like skin cells and the kidney cells start to look more like liver cells and they what we call x differentiate |
| 27:48 | 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 |
| 27:54 | that process of x differentiation the loss of the reader of the the cd or the dvd |
| 28:01 | we liken that to scratches on the dvd so that the reader cannot |
| 28:07 | fully access the information now we can slow down the scratches as i mentioned we can turn on these genes we |
| 28:13 | can even put in molecules into the cell or even eat them and turn on those pathways which |
| 28:19 | which my father and i have been trying to do for about a decade to slow things down but the question |
| 28:25 | that i've had is is there a repository of information still in the body |
| 28:30 | because anyone who knows anything about the loss of information or even has tried to copy a cassette tape or |
| 28:36 | photocopy or xerox anything knows that over time you you lose that information irreparably |
| 28:41 | so i've been looking for a backup copy inspired largely by claude shannon's work at mit as well in the 1940s |
| 28:49 | his theory mathematical theory of communication is just brilliant and so i've been looking for what he called the observer |
| 28:55 | which is the backup copy we today might call that the tcpi pro tcp ip protocol of the internet that |
| 29:01 | stores information in case it doesn't make it to your computer it will fill in the gaps and we've been |
| 29:07 | 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 |
| 29:14 | scratches away that's incredible so finding the backup so whenever there are too many scratches |
| 29:20 | pile up you can just write a new version like right that not every new version |
| 29:26 | but go to the backup and restore it right that's really all we're talking about it's not that hard |
| 29:32 | once you know the trick and for people that actually remember uh like dvds and scratches on them how |
| 29:39 | frustrating it is that that's a brilliant metaphor for aging |
| 29:45 | and then the the reader is uh is the thing that skips and then it |
| 29:51 | could destroy your experience the richness of the experience that is uh listening to your favorite song |
| 29:57 | 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 |
| 30:03 | and we call that aging and age-related diseases so it's it most people forget that |
| 30:09 | diseases that we get when we get old are 80 to 90 caused by aging and we've been trying to |
| 30:14 | fix things with band-aids after they occur without even generally talking about the root cause of the problem |
| 30:21 | is there um the scratches do those come from |
Why do we age?
| 30:28 | are those programmed or are they failures meaning is it so if it's |
| 30:35 | by design then there's like a encoded timeline schedule that the body's just |
| 30:42 | on purpose degrading the whole thing and then there's the just the wear and tear of like the scratches |
| 30:48 | and a disc that happen uh through time which which one is it that's the source of aging |
| 30:53 | 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 |
| 31:01 | 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 |
| 31:06 | thermodynamics stuff falls apart we live a bit longer than age 40 only because there are robust resilient |
| 31:12 | systems but eventually they fail as well current limit to the human lifespan where they completely fail is 122. |
| 31:19 | 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 |
| 31:26 | system that's built to keep us alive when we're young but actually ghost comes back to bite us |
| 31:32 | as we get older and we call this this issue antagonistic pleiotropy what's good for |
| 31:38 | you when you're young can cause problems when you're older so we've been looking what what is the |
| 31:44 | cause of the main causes of the noise and we've come we found two of them definitively |
| 31:49 | the first one is broken chromosomes when a chromosome breaks the cell has to panic because that's |
| 31:55 | 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 |
| 32:02 | does is it reorganizes the epigenome in a massive way |
| 32:07 | what that leads to is think of it as a tennis match or a ping pong game the proteins are the bowls and they |
| 32:14 | now leave where they should be which is regulating the genes that make the cell type whatever it is |
| 32:19 | and they have to they have a dual function they actually go to the break the chromosome will break and fix that |
| 32:25 | 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 |
| 32:31 | expression the control systems with the repair you want them coordinated problem is as we get older this ping |
| 32:37 | 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 |
| 32:44 | noise for aging and we've also the other cause of aging that we found is is cell stress |
| 32:50 | we damage nerves and they age rapidly so you that's the other issue there's probably others |
| 32:56 | smoking chemicals for example we know accelerates biological age pretty dramatically |
| 33:02 | 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 |
| 33:07 | originally started in the game and we think we've found a way to do that what can you give me hints |
| 33:13 | uh whose fault is it and the ball's not coming back is it the proteins themselves like are they are they starting again |
| 33:20 | 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 |
| 33:27 | um and recruits them so that the brake uh is recognized by proteins who send |
| 33:33 | out a signal uh through phosphorylation is typical way cells talk |
| 33:38 | to other proteins and that recruits those repair factors those ping-pong balls to |
| 33:44 | the brake so the cell's actively doing this to try and help itself but we don't know |
| 33:50 | who's to blame for them not coming back um that could just be a flaw in the |
| 33:56 | quote-unquote design i don't think that there's something saying well one percent of you you bowls |
| 34:02 | proteins never go back i just think it's hard to reset a system that's constantly changing |
| 34:07 | we have in our bodies close to a trillion dna breaks every day |
| 34:12 | and imagine that over 80 years what damage that does to our epigenomic information now we know that this is well i should |
| 34:20 | we never know anything in biology but we have strong evidence that this is true because we can |
| 34:25 | mess with animals we can create dna breaks and tickle them with a few breaks maybe |
| 34:31 | raise it by threefold over background levels of normal breakage and if we're right those mice |
| 34:37 | should get old and they do we can actually we've we've created these breaks in a way that's |
| 34:43 | 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 |
| 34:49 | fan of of spinal tap two going to 11. if we go to 11 we can make a mouse old in a matter |
| 34:54 | of months we prefer to go to a level of about four and it gets old in 10 months |
| 35:00 | but it's definitely old it's got all of the hallmarks of aging it's got diseases it looks old its skin |
| 35:06 | 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 |
| 35:12 | measure it and use machine learning to give us a number and those mice are 50 older than normal |
| 35:19 | so you can replicate the aging process in a controlled way you can all i mean in a way that you i mean you |
| 35:24 | could accelerate it in a controlled way and measure how much |
| 35:29 | exactly it's aging and that gives you step one of a two-step process to when you can |
| 35:35 | then figure out what how can we reverse this and now we're reversing those mice is there a good |
| 35:41 | i love what you said i mean in biology you really don't know it's it's such a beautiful mess uh |
| 35:48 | is is there is there ideas how to do that is that on the genetic engineering level is that uh |
Genetic reset switch that reverses aging
| 35:55 | like what can you mess with is it going to the trying to discover the backup copies |
| 36:02 | and restoring from them like what's if it's it's possible to convert it into natural language words |
| 36:08 | what are the ideas here what is the observer and how do we contact it exactly what's the observer and how do |
| 36:13 | you contact or if there's other ideas how to reverse the the the boss getting |
| 36:19 | lost process yeah well you you can slow it down slow it but we found a reset switch recently we |
| 36:26 | just published this in the december 2020 issue of nature |
| 36:32 | and what we found is that there are three embryonic genes that we could put into the adult |
| 36:38 | animal to reset the age of the tissues and it only takes four to eight weeks to work |
| 36:43 | well and we can take a blind mouse that's lost its vision due to aging neurons aren't working well towards the |
| 36:49 | brain reset those neurons back to a younger age and now the mice can see again these |
| 36:55 | three genes are famous actually because they're a set of four genes discovered by shinya yamanaka who won |
| 37:01 | the nobel prize in 2016 for discovering that those four genes when turned on |
| 37:07 | at high levels in adult cells can generate stem cells and this is i think well |
| 37:13 | 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 |
| 37:20 | a tumor or generating a stem cell in the eye which would be a disaster and the answer is yes there is a system |
| 37:25 | in the body that can take the age of a cell back to a certain point but no further safely and reset the age |
| 37:33 | and uh we're now using that to reset the age of the brain of those mice that we age prematurely |
| 37:39 | and they're getting their ability to learn back this is really exciting right like |
| 37:44 | what's uh what's the downside of this well the downside is if you overdo it and you don't get it right |
| 37:50 | uh you might cause tumors but we do we do it very carefully and we also know |
| 37:55 | that in the eye it's very safe yeah we also injected these we deliver them by viruses so |
| 38:02 | we can control where and when they get turned on and in this paper we've published that |
| 38:08 | if we put high levels in the mouse into their veins throughout the body they don't get cancer for over a year |
| 38:14 | so i'm so optimistic that we're going into human studies in less than two years from now is there |
AI in biology
| 38:20 | a place where ai can help sorry to inject one of the things i'm |
| 38:27 | very excited about i'm passionate about so uh deep uh google deep mind |
| 38:33 | recently had a big breakthrough with alpha fold two but also half a fold two years ago with um |
| 38:41 | achieving sort of uh state-of-the-art performance on the protein folding |
| 38:47 | problem single protein folding but it also paints a hopeful picture of |
| 38:52 | what's possible to do in terms of simulating the folding of proteins but also simulating biological systems |
| 38:59 | through ai is there something to you combined with this brilliant work on |
| 39:05 | the biology side that you're hopeful about where ai can be a tool to help where isn't that a |
| 39:11 | 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 |
| 39:16 | biological clocks to be able to read those scratches we're using it to predict the folding of |
| 39:23 | proteins so we can target molecules and modulate their activity we're using it to assemble |
| 39:28 | genomes of different species what else we use it to predict the longevity of a |
| 39:35 | mouse based on how it reacts to certain things hearing eyesight generally frailty so we |
| 39:41 | have we just put out a paper last year on that um the other thing we can use it for which |
| 39:46 | is a little off the track here but we use it for predicting which microorganisms are in your body |
| 39:53 | actually not predicting telling you so our daughter natalie was infected with |
| 39:59 | lyme disease a few years ago almost went blind from it and the test took four days and i thought |
| 40:05 | 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 |
| 40:11 | this has to be done better so i've started a company that now can take a sample of any |
| 40:16 | part of your body it's typically done now with transplant liver transplant patients to detect |
| 40:22 | viruses that come out of their organs but that's that's another area that ai is extremely |
| 40:27 | important for um i i think if you're not in five years if you're not using |
| 40:33 | you know deep learning you've got a problem because the amount of data that we generate now as biologists |
| 40:38 | is just terabytes can be terabytes per week it'll eventually be terabytes per day and then we just go from there and i |
| 40:44 | actually have trouble recruiting enough bioinformaticians a lot of our work is |
| 40:49 | now just number crunching a part of that is collecting the data |
Health data
| 40:55 | which is kind of something we've talked a little bit about but is there something you can say |
| 41:00 | about how we can like can collect more and more data not just on the one person level |
| 41:07 | like for you to understand your like various markers but to create |
| 41:14 | huge data sets to understand how we can detect certain pathogens detect certain |
| 41:21 | properties characteristics of whether it's aging or all the other ways the human body can fail |
| 41:27 | it seems like with the with biology there's a kind of privacy concerns that well actually not |
| 41:34 | privacy concerns it's almost like regulation that kind of prevents like hospitals and |
| 41:39 | sharing data um you know i'm not sure exactly how to say it but it |
| 41:45 | seems like when you look at autonomous vehicles people are much more willing to share data |
| 41:50 | when you look at human biology system people are much less willing to share data is there a hopeful path forward where we can |
| 41:57 | share more and more data at a large scale that ultimately ends up helping us |
| 42:02 | understand the human body and then treat problems with the human body so we are right in the middle |
| 42:08 | 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 |
| 42:15 | bodies and 20 years ago people didn't want to go on social media they're worried about it now |
| 42:20 | you have to if you're a kid that's for sure same with medical records these are |
| 42:25 | becoming all digitized and and expanded ultimately we're going to |
| 42:31 | even if we don't want to have to be monitored there's going to be a court case that i |
| 42:37 | 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 |
| 42:44 | and you didn't use it lawsuit right there and suddenly all hospitals have to give you one of these there will be a |
| 42:49 | reversal like to where it's your fault if you don't collect the data that's brilliant |
| 42:55 | that's and that's absolutely right i mean that's absolutely right that's the frustration |
| 43:01 | i feel when going to the doctor is like you're it's almost negligent |
| 43:08 | to not collect the data because you're making if there's something really wrong with me |
| 43:13 | and you're making decisions based on very few tests that's almost negligent when you have |
| 43:19 | the opportunity to collect a huge amount more data well like let me tell you something yeah like the |
| 43:25 | i've got this inside tracker data for for myself over a decade and you'd think my doctor would roll his |
| 43:31 | eyes at this oh he's gone to a consumer company blah blah blah i had my first checkup in a year with |
| 43:36 | him through video conference and he was running |
| 43:42 | 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 |
| 43:48 | kind of usual things and i said well i've got new tests back from inside tracker and he said |
| 43:54 | great i'd love to see them so i share screen and we look at the graphs look at the data |
| 43:59 | and he's loving it because he cannot order these tests willy-nilly so i said well let's order a |
| 44:06 | hba1c blood glucose levels because i'm very interested in that that tracks with longevity and he says well |
| 44:12 | i have no reason to order that do you have a family history no uh are you have any symptoms of |
| 44:18 | diabetes no well i can't order the test i almost wanted to reach through the computer and strangle him um |
| 44:23 | 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 |
| 44:30 | 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 |
| 44:36 | educate me i've i think doctors sometimes have a little bit of an ego |
| 44:42 | i understand that the doctor is super experienced a lot of things but this is a fundamental question of human |
| 44:48 | variability like i know a lot of specific details about like um i mean depending of course what we're |
| 44:54 | talking about but there's a i bring a lot of knowledge and if i have data with me then i have |
| 44:59 | like several orders of magnitude more knowledge and i think there's an aspect to where the doctor has to |
| 45:06 | put their expert hat like take it off and actually be a curious |
| 45:13 | open-minded person and study and look at that data do you think it's possible to sort of |
| 45:18 | change the culture of the medical system to where the doctors are almost as you said are excited to see the data |
| 45:25 | or that's already happening it's really happening now we've probably lost the last generation um that they're no hopers but |
| 45:32 | so i teach at harvard medical school and they're excited about this they're excited about aging which is a |
| 45:37 | new aspect to medicine oh wow we can do something about that and then yeah all this data what do we |
| 45:43 | do with it there's still the traditional pathology and all that stuff which they need to know but time will change their |
| 45:50 | their uh mindset i'm not worried about that and like we were discussing this isn't a |
| 45:56 | 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 |
| 46:02 | i had breakfast with with the ceo who uh is making this happen uh just |
| 46:07 | yesterday i can tell you for sure that most people have no idea that this revolution |
| 46:13 | is occurring and is happening so quickly uh if you're running a hospital and you can save two thousand dollars per |
| 46:20 | cardiac patient what are you gonna do you have to use it otherwise you know the hospital down the road's |
| 46:25 | gonna be beating you um and there are large hospital aggregations so there's ascension and |
| 46:31 | others that just have to go this way for budgetary reasons and right now the |
| 46:38 | u.s spends what is 17 of their gdp on healthcare for let's say one of these |
| 46:44 | buttons on my chest cost 20 bucks it's rechargeable and it can predict people's health and save on antibiotics |
| 46:50 | prevent heart attacks how many billions if not trillions of dollars will that save over the next decade |
| 46:58 | 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 |
| 47:04 | 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 |
| 47:12 | companies are going to want to get in on this so now that gets to privacy right if |
| 47:17 | should an insurance company have access to your data i would say no but you could voluntarily show them |
| 47:23 | some of it if they give you a discount and that's also being worked on right now |
| 47:28 | i hope we do create kind of systems where i can volunteer to share my data and i can also |
| 47:34 | take the data back meaning like delete the data request the deletion of data and then maybe policy creates rules to |
| 47:41 | where you can share data you could delete the data and i think if i have the option to |
| 47:48 | delete all my data that that a particular company has then i'll share my data with everyone |
| 47:55 | like i feel like uh if the if uh because that gives me the tools to be a |
| 48:02 | consumer an intelligent consumer of giving of awarding my data to a company that |
| 48:07 | deserves it and taking it back when the company is misbehaving and in that way encourage as a consumer |
| 48:14 | in the capitalist system encourage the companies that are doing great work with that data |
| 48:20 | well yeah health care data security is is number one on on my mind uh inside tracker |
| 48:26 | made sure that that was true but you know these buttons on your chest there's very private stuff they can probably tell |
| 48:33 | 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 |
| 48:38 | blockchain or just for yourself i don't want this public life i guess it depends on how you how |
| 48:44 | 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 |
| 48:51 | 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 |
| 48:57 | yeah so there's on the biology side super exciting ways to um to slow aging but there's also on the |
Fasting
| 49:04 | lifestyle side i've recently did a 72 hour fast it's just an opportunity to take a pause and |
| 49:09 | be you know appreciate life think about like there's something about fasting that um |
| 49:16 | encourages you to reflect deeper than you otherwise might the time kind of |
| 49:22 | slows and you also realize that you're human because your body needs food and you start to see your |
| 49:29 | is almost as a machine that that takes food and produces thoughts and then |
| 49:35 | and then ends briefly i mean there you start to depending who you are if you're like engineering minded you |
| 49:41 | start to think of this whole thing as a kind of yeah as a machine and then also feelings fill this machine |
| 49:50 | uh feelings of gratitude of love but also the uglier things of jealousy and greed |
| 49:57 | and hate and all those kinds of things you start to think okay how |
| 50:03 | 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 |
| 50:10 | to fasting i intermittent fast a lot i eat just one meal a day |
| 50:15 | most of the time is there something you can say about the benefits of fasting in your own life |
| 50:20 | and in general the anti-aging process well you're a philosopher too sorry i |
| 50:26 | apologize no i'm impressed uh through renaissance man uh it's it's a joy to be here |
| 50:31 | uh so when it comes to fasting this is you know being abstinence is one of the the oldest ways to improve health right |
| 50:38 | probably they knew this 5000 plus years ago so that's not new but what we're |
| 50:43 | figuring out is what is optimal and how does it work and one of the things we helped contribute to |
| 50:49 | which i can speak to with some authority is that these longevity genes we work on we showed back in the early 2000s are |
| 50:56 | turned on by fasting and at least in yeast we were the first to show that how calorie restriction |
| 51:02 | fasting works to extend lifespan that was the first for any species something similar happens in our bodies |
| 51:08 | when we're hungry or put our bodies under any other perceived adversity such as running |
| 51:14 | our bodies think wow we're getting run chased by a cyber save tooth cat or something if we're |
| 51:19 | really hot or cold these probably also work to put our bodies in this defensive state to activate these genes in the way |
| 51:26 | that whales do and mice don't and so hunger is the best way to do that |
| 51:31 | 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 |
| 51:36 | recommend to anybody to slow down aging would be to skip a meal or two |
| 51:41 | 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 |
| 51:48 | possible but i've gone from skipping breakfast most of my life now to skipping lunch as well and i have |
| 51:56 | my physique back that i had when i was 20. i feel 20 mentally i'm much sharper i don't |
| 52:02 | 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 |
| 52:08 | beyond one day but have you ever fasted longer than uh than them 24 hours i tried doing two |
| 52:16 | 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 |
| 52:22 | 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 |
| 52:29 | if i can do that seriously anybody can do that um to your listeners and viewers i would say |
| 52:35 | don't try to do it all at once you can't go from snacking and eating three meals a day to what i |
| 52:41 | 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 |
| 52:48 | um that's fine you can fill your stomach up with with liquids uh diet sodas i get criticized for |
| 52:53 | 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 |
| 52:59 | 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 |
| 53:05 | in your mouth chewing feeling that fullness you can break that habit and within two three weeks you'll have done it |
| 53:12 | absolutely so i'm not actually even that strict about it you said that soda uh yeah people are very kind of weirdly |
| 53:18 | strict about fasting the rules and the fasting like for example i i drank |
| 53:23 | uh element electrolytes when i was fasting and that has like five calories and so technically it's uh |
| 53:30 | not fasting or people will say like if you drink coffee there's caffeine and they'll say that's technically not |
| 53:36 | fasting because there's some kind of biological effects of caffeine whatever of course there's like biological benefits that you can argue |
| 53:43 | about but there's also just experiential benefits just calorie restriction broadly has a |
| 53:48 | certain experience to it that like for me personally just as you said has made me feel really good |
| 53:55 | that said like especially uh i've gained quite a bit of weight uh like maybe even |
| 54:01 | like 15 pounds something like that since i moved to austin texas and i i still keep the same diet but |
| 54:09 | i eat a lot of meat in that one just because it's delicious because it's |
| 54:14 | also the the the amazing people i met in texas it's just there's like a camaraderie a |
| 54:21 | friendship of love to the people that like makes you really enjoy the uh the atmosphere of eating the |
| 54:28 | brisket and the meat is this joe rogan insisting joe is i mean he's very different |
| 54:33 | uh joe loves bread and pasta like he knows that his body |
| 54:40 | feels best doing keto or carnivore so that's what he usually tries to stick |
| 54:46 | to but he also does not hold back and he'll just eat pasta when he does |
| 54:52 | pasta and he sort of enjoys life in that way i can't i don't know how to enjoy life |
| 54:57 | in that way i also love pasta but i'm just not going to enjoy it because i know |
| 55:03 | i i know my body ultimately does not feel good with pasta so it's a funny kind of dichotomies i i |
| 55:09 | would like to uh cheat i guess by eating more meat than i you know like |
| 55:17 | overeating uh on the things that i know my body feels good on as opposed |
| 55:22 | to eating stuff i shouldn't like cake and all those kinds of things i tend to um i tend to find happiness in |
| 55:30 | overeating the good stuff versus eating the bad stuff and the that's the |
| 55:36 | kind of balance him he's like [ __ ] it every once in a while you got to enjoy |
| 55:42 | it and and then also coupled with that for him uh is just exercise like then faces |
| 55:49 | demons the next day and just like burn a huge amount of calories which is i mean |
| 55:55 | whatever whatever is up with that guy's mind there's an there's a ability to fully |
| 56:02 | experience life which is represented by the pasta and the ability to just like fight the |
| 56:08 | 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 |
| 56:15 | out of you doing that kind of insane exercise and i think i'm more like you at least |
| 56:20 | towards your direction is like i really hate exercise so i do it but i |
| 56:25 | really hate it and so it's a balance that you have to strike is there something you could say about |
Diet
| 56:31 | the diet side of that for you personally but in general in order to achieve |
| 56:37 | calorie restriction like for me eating i know it may not |
| 56:43 | sound healthy but eating carnivore eating mostly meat has been has made me feel really good |
| 56:50 | both mentally and physically is there something you could say about the kinds of diets |
| 56:56 | that may improve longevity but also enable calorie restriction well sure i mean the first thing that's |
| 57:03 | important to know is that while many people are interested slash obsessed with |
| 57:09 | what they eat the data that's come out of animal studies at least is it's far more important when you eat |
| 57:16 | than what you eat and this was a fantastic study a few years ago by my friend rafael de cabo at the national |
| 57:22 | institutes of health in bethesda and he had 10 000 mice on different diets hoping to find the perfect mix of |
| 57:28 | carbs protein and fat and it turns out that the only ones that lived longer were the ones that only ate |
| 57:34 | once a day and so that if we're we're not mice but i think that we're close enough to mice |
| 57:40 | 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 |
| 57:48 | less often and eat the right things now i'll preface this to say i'm not a nut about this i will eat |
| 57:55 | occasional very occasionally a dessert usually i steal from others which doesn't count right |
| 58:00 | 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 |
| 58:07 | 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 |
| 58:14 | on a steak which i did a couple of days ago i actually had a chicken uh a fried chicken specifically |
| 58:22 | 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 |
| 58:27 | want to binge on meat and fried foods i just can't it just feels bad |
| 58:32 | but what what do i recommend well what the data says which i try to follow is that |
| 58:38 | plant-based foods will will be better than meat-based foods and i know that there are a lot of people disagree |
| 58:43 | 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 |
| 58:50 | diet they're eating mostly plants with a little bit of meat and not a lot of red meat and the other |
| 58:56 | 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 |
| 59:03 | to certain amino acids that are found in more abundance in meat and when it responds it actually |
| 59:08 | shortens lifespan and the converse if you starve it of those three amino acids uh in mostly in meat |
| 59:15 | then it extends lifespan and there there's a drug called rapamycin which some people are experimenting with |
| 59:21 | 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 |
| 59:27 | here but you could potentially take a rapamycin-like drug and counteract the effects of meat on in |
| 59:32 | 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 |
| 59:39 | what i think is going on is that just like testosterone and growth hormone you will get temporary |
| 59:45 | maybe not temporary um immediate health benefits you'll feel great you'll get more muscle |
| 59:50 | energy but the problem is i think it's at the expense of long-term health and longevity |
| 59:57 | well this is actually something i worry about in terms of long-term effects or |
| 1:00:04 | the the cost in terms of longevity it's very difficult to know how your choices affect your longevity |
| 1:00:09 | because the impact is down the line like just because something makes me feel |
| 1:00:16 | good now like eating only meat makes me feel good now i wonder what are the costs down the |
| 1:00:21 | line well think about what i i was saying about the trade-offs between growth and reproduction which is what a |
| 1:00:27 | mouse does and a whale that grows slowly reproduces slowly lives a long time |
| 1:00:32 | it's called the disposable soma theory um kirk would just uh propose that in the 70s what meat |
| 1:00:39 | probably does is put you in the mouse category super fertile grow fast heal fast |
| 1:00:44 | and then if you want to be a whale you should restrict meat uh and do things that promote the |
| 1:00:51 | preservation of your body is it uh difficult to eat a plant-based |
| 1:00:56 | diet that uh you perform well under so uh mentally and physically just |
| 1:01:02 | almost i'm asking uh almost like a anecdotal question unless you know the science |
| 1:01:09 | uh well the science is still being worked out but from the synthesis of everything i've read i try to |
| 1:01:16 | eat a diet that's definitely full of leafy greens uh particularly spinach is great because |
| 1:01:22 | it's got the iron that we need plenty of vitamins i also |
| 1:01:27 | try to avoid too much fruit and berries particularly fruit juice |
| 1:01:33 | definitely avoid that sugar high spiking your sugar is not healthy in the long run |
| 1:01:39 | the other thing that's interesting is we discovered what are called what we call xeno hormetic molecules let me unpack |
| 1:01:46 | that because it's terrible name and i take full responsibility with my friend conrad howitz the xeno means cross |
| 1:01:52 | species and hormesis is the term that what doesn't kill you makes you live longer |
| 1:01:59 | and and and be healthier and so we're getting cross species health improvements by molecules |
| 1:02:05 | that plants make and plants make these molecules when they're also under adversity or perceived adversity for instance uh |
| 1:02:13 | i understand if you want really healthy or good oranges you can drive nails into the the bark of |
| 1:02:18 | the tree before you harvest same with wine you typically want them to be dry before you harvest |
| 1:02:24 | or covered in fungus and that's because these plants make these colorful and xenohemetic molecules that make |
| 1:02:31 | themselves stress resistant turn on their sirtuin defenses the sir genes remember |
| 1:02:37 | 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 |
| 1:02:42 | coincidence it's my theory our theory that we want to know when our food supplies |
| 1:02:48 | is under adversity because we need to get ready for a famine and so we hunker down and preserve our |
| 1:02:53 | body and by eating these colored foods so practically speaking if it's full of color or if there's been some chewing by |
| 1:03:00 | a caterpillar caterpillar organic grown locally in local farms i'll eat that |
| 1:03:05 | versus a watery insipid uh light-colored um lettuce that's been grown in |
| 1:03:12 | california so you want vegetables that have suffered you want the david goggins as the vegetables that's the xenochromatic molecules i |
| 1:03:19 | love that tone i'm gonna take that one with me thank you yeah |
| 1:03:24 | oh i follow him on instagram is always screaming so you want the that he's basically uh the the |
| 1:03:31 | the xeno-harmonic version of a human um i like it so these are the molecules |
| 1:03:37 | that are representative of the stress that's been um that a plant has been under yeah the |
| 1:03:44 | best example of that is resveratrol which many people including myself take as a supplement grapes or grape |
| 1:03:51 | vines produce that in abundance when they're dried out or they have too much light or fungus |
| 1:03:56 | and that we've shown activates the so2 enzyme in our bodies which remember is |
| 1:04:02 | what extends lifespan in yeast and slows down aging in the brain that's beautiful yeah i tend to avoid fruit |
| 1:04:08 | as well so green veggies anything that's not very sweet so i would just say you're relatively |
| 1:04:14 | low like you try to avoid sugary things as well yeah i'm fairly militant about |
| 1:04:20 | that um i rarely would add sugar to anything occasionally i would um |
| 1:04:26 | eat a slice of cheesecake but that would be you know maybe once or twice a year you have to give in occasionally but |
| 1:04:33 | yeah anything that's sweet i would rather substitute something like stevia if i need a sugar hit |
Exercise
| 1:04:40 | what about exercise your favorite topic is there uh is there anybody talking |
| 1:04:47 | about it yeah okay great is there benefits to longevity from exercise well no doubt that's |
| 1:04:54 | that's proven um just like fasting it's pretty clear that that works uh for example there are studies of |
| 1:05:00 | cyclists it was something like people that cycle over 80 miles a week |
| 1:05:06 | have a 40 reduction in a variety of diseases certainly heart disease so that that's not even a question but |
| 1:05:11 | what's interesting is that we're learning that you don't need much to have a big benefit it's an asymptotic curve |
| 1:05:17 | and in fact if you overdo it you probably have reduced benefits particularly if you start to wear out joints that kind of thing |
| 1:05:23 | but just 10 minutes on a treadmill a few times a week getting your lose your breath get hypoxia because it's cold |
| 1:05:28 | seems to be very beneficial for long-term health um and that's the kind of exercise that |
| 1:05:34 | i like to do aerobic though i do enjoy uh lifting weights so that is what i call my exercise which |
| 1:05:40 | has other benefits including maintaining hormone levels male hormone levels |
| 1:05:46 | but also really why i do it is i want to be able to counteract the effects of sitting for |
| 1:05:52 | most of the day yeah and as you get older you lose muscle mass it's a percent or so a year |
| 1:05:57 | 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 |
| 1:06:02 | in this country so maintaining that strength but also doing the cardio for the longevity for |
| 1:06:08 | the avoiding the heart disease yeah i definitely just like with fasting |
| 1:06:13 | have the philosophical benefit of running long and running slow i enjoy because it kind of clears the mind and |
| 1:06:19 | allows you to think and actually listen to brown noise as i run it really helps |
| 1:06:24 | remove myself from the world and just like zoom in on particular thoughts what is brown noise it's like white |
| 1:06:30 | noise but deeper so like the white noise is like shh and then brown noise is more like |
| 1:06:38 | like ocean that sounds great i might try that yeah yeah it's a small sweet thing probably |
| 1:06:44 | 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 |
| 1:06:52 | this is maybe like five years ago i started listening brown noise when i work and uh the first time i listened to it |
| 1:06:58 | something happened to my mind where it just went like zoomed in |
| 1:07:03 | to like in a way that it felt like really weird like how how precisely was able to sort |
| 1:07:11 | of remove the distractions of the world and really help my mind obviously like the |
| 1:07:17 | 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 |
| 1:07:24 | this is generalizable to others people should definitely try it if you're listening to this maybe it's just my own mind but |
| 1:07:31 | it's funny like it made me brown noise made me realize that there's probably |
| 1:07:36 | hacks out there that work for me that i should be constantly looking for it's almost like |
| 1:07:42 | um an encouraging and motivating of event that maybe there's other stuff |
| 1:07:49 | out there maybe there's other brown noise like things out there that truly like almost immediately make me |
| 1:07:55 | 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 |
| 1:08:02 | many others things like that that could be discovered and so it's always disappointing when i find |
| 1:08:09 | things in life that i wish i had found earlier like i got lasik |
| 1:08:14 | eye surgery a few years ago and the first thought i had like the next day when i woke up is like |
| 1:08:21 | damn it why didn't i do this way earlier there's other stuff of that nature that um they're yet to be |
| 1:08:29 | discovered so it pays to explore yeah though you have a different mind you have quite a beautiful mind so i |
| 1:08:34 | suspect brown noise helps you focus and because you're probably all over the place if you don't control it |
| 1:08:40 | yeah exactly i mean it's something about it it's a programmer thing i don't the programming is a really difficult |
| 1:08:47 | um mental journey because you have to keep a lot of things in mind |
| 1:08:52 | you have to uh so you're constantly designing things and you have to be extremely precise by |
| 1:08:58 | making those things concrete in code you also have to look stuff up on the |
| 1:09:04 | internet to sort of feed like information and looking up stuff on the internet |
| 1:09:10 | 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 |
| 1:09:17 | requires a certain discipline and a certain focus that uh i've been very much exploring |
| 1:09:23 | 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 |
| 1:09:30 | uh keeping very positive inspired no social media all those kinds of things and trying to optimize for and everybody |
| 1:09:36 | has their own kind of little journey that they try to understand you get this from like writers |
| 1:09:41 | when you read about the habits of writers like the habits they do in the morning |
| 1:09:47 | they usually write like two three four hours a day and that's it it's like they optimize that ritual and |
| 1:09:53 | then there's always hunters thompson so uh |
| 1:09:59 | sometimes it pays off to be wild what about the sleep how important is sleep for |
Sleep
| 1:10:05 | longevity i would guess based on the evidence that |
| 1:10:10 | it's really important and because we don't know for sure but what we know from animal studies |
| 1:10:16 | is the following if you restrict sleep from a rat for just two weeks it'll develop type 2 diabetes it's that important |
| 1:10:24 | so that's the main thing what we also know is at the molecular level that if you disrupt your |
| 1:10:31 | 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 |
| 1:10:39 | you disrupt that you'll get premature aging and guess what the opposite is true that as you get older |
| 1:10:45 | that cycle the the amplitude becomes diminished and this is why it's harder to get to |
| 1:10:50 | sleep as you get older and then you've got all sorts of problems and i think what's going on is this positive |
| 1:10:56 | feedback loop which is is a disaster in your old age which is um |
| 1:11:01 | right you're aging you can't at this moment totally prevent that and then it's disrupting your sleep then you get not |
| 1:11:07 | enough sleep and then that's going to accelerate your aging process um and so it's known that that people |
| 1:11:12 | who are shift workers are more susceptible to certain age-related diseases so your |
| 1:11:17 | 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 |
| 1:11:24 | what i do the day before if it was a bad idea and i'll stop doing that like eating a fried chicken |
| 1:11:31 | i see you're still carrying the burdens of that decision but is yeah you know sleep is one of |
| 1:11:37 | those things that's making me wonder about the variability between humans a little bit and how |
| 1:11:43 | science is often focused on like it's not often focused on high |
| 1:11:50 | performers in a particular way and it's looking at the aggregate versus the individual cases |
| 1:11:57 | for example like for me i don't know what the exact hours are but like power naps are incredible |
| 1:12:06 | i tend to look at the metric of stress and happiness and joy and try to optimize those so |
| 1:12:13 | decreasing stress increasing happiness and using sleep as just one of the tools |
| 1:12:18 | to do that because like hitting the five six seven eight nine hour mark or whatever the |
| 1:12:25 | correct mark is i find that to be stress inducing for me versus |
| 1:12:30 | stress relieving like thinking about that i i feel best if i sleep sometimes for |
| 1:12:36 | eight hours sometimes for four hours and then power nap and as long as i have a stupid private |
| 1:12:42 | usually smile on my face that's when i'm doing good as opposed to getting |
| 1:12:47 | a perfect amount of sleep according to whatever the latest blog post is and i also pull |
| 1:12:54 | all-nighters still i also think there's something about the body like as long as you do it |
| 1:13:01 | regularly it's not as stress-inducing like you know what you know what it is the reason i pull |
| 1:13:07 | all-nighters isn't for like i'm playing diablo 3 or something is because i'm doing something i'm truly |
| 1:13:13 | passionate about well i can also love video games but i'm doing something i'm truly passionate about |
| 1:13:18 | 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 |
| 1:13:24 | night and still i'm working on it there's a kind of a celebration of the human spirit that i really enjoy it |
| 1:13:30 | like uh and that's happiness and to sort of then and i usually don't tell that kind |
| 1:13:37 | of stuff to people because their first statement will be like you should get more sleep |
| 1:13:42 | it's like no i'm doing stuff i love you should get more love in your life |
| 1:13:47 | bro that's right so but that said in aggregate when you look at the full span of life |
| 1:13:55 | it's probably you should be getting a consistent amount of sleep and it |
| 1:14:01 | seems like it's in that seven eight hour range yeah but it's similar to food |
| 1:14:06 | 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 |
| 1:14:14 | and what makes a difference to me is not the amount of hours but the quality the depth and the deep sleep |
| 1:14:20 | 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 |
| 1:14:26 | 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 |
| 1:14:32 | so that like you say if you're happy and contented and you're not don't have these cortisol chemicals going through your |
| 1:14:37 | 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 |
| 1:14:45 | 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 |
| 1:14:52 | 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 |
| 1:14:58 | energy drinks i could probably uh sleep so that i don't know if that's genetics or |
| 1:15:04 | 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 |
| 1:15:10 | i'm almost listening to some kind of biological signal versus societal signal on when i'm supposed to |
| 1:15:16 | go to sleep so i just go to sleep whenever i feel like going to sleep well that's because you're |
| 1:15:21 | 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 |
| 1:15:27 | um but yeah it's super important and those people who have the shift work i mean they they really |
| 1:15:33 | need to to change the way that works because they're literally killing those people |
| 1:15:38 | is there something you can say about the the mind and stress |
| 1:15:45 | uh in terms of effect on longevity sort of um because i don't know if you |
| 1:15:51 | think about it this way but when you talk about the biological machine it's always these mechanisms |
| 1:15:56 | that don't are not necessarily directly connected to the brain or the operation of the brain like |
| 1:16:02 | what's the role about stress and happiness and uh |
| 1:16:08 | yeah the sort of higher cognitive things going on in the brain on longevity right well that's a great |
| 1:16:15 | point that the brain is is the center for longevity actually we we do know that first start when when |
| 1:16:21 | i'm stressed i can see mentally stressed then i can see it in my body |
| 1:16:27 | heart rate hormones it's clear you know that's no true surprise so you've got to work on |
| 1:16:32 | your brain first and foremost if you are totally freaked out agitated uh |
| 1:16:38 | all the time you will live shorter i'm certain of it you know i keep fish i'm a big |
| 1:16:46 | aquarium guy and you can see the difference between the the fish that's having a good time and dominant |
| 1:16:51 | 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 |
| 1:16:58 | it so i used to be extremely stressed as a kid i was a perfectionist very shy always worried about being a |
| 1:17:04 | 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 |
| 1:17:12 | 30s and realized that's not the way to live so i've worked very hard to get to this point |
| 1:17:17 | where i almost never get stressed never there's nothing that i've never gotten angry in my lab i've |
| 1:17:23 | got 20 kids sometimes it's like a most of the time it's like a kindergarten um i |
| 1:17:29 | haven't lost my temper i very calm but that's intentional um and i don't worry about stuff |
| 1:17:34 | millions of dollars billions of dollars at stake sometimes keep it cool it's only life we're all |
| 1:17:40 | headed to the same place anyway don't worry about it um but the the to answer your question i think |
| 1:17:46 | in a better way if you manipulate the brain of an animal i'll give you an example if we turn on |
| 1:17:51 | this cert gene that i mentioned sir one we a good friend of mine that wash you shiny my did this |
| 1:17:58 | they upregulate the operate of that gene just in the neurons of the animal |
| 1:18:03 | it lived longer so that's sufficient to extend lifespan we also know that you can manipulate the |
| 1:18:08 | part of the brain called the hypothalamus which leaches a lot of chemicals into the body |
| 1:18:13 | and proteins most of which we don't know yet but just changing the inflammation of that little organ |
| 1:18:20 | or part of the brain is sufficient to make animals live longer as well so get your brain in order first before |
| 1:18:26 | you tackle anything else i would say so you kind of mention this with the |
Data
| 1:18:32 | inside tracker there's a ability to take blood measurement and then infer from that |
| 1:18:39 | a bunch of different things about your body how you can improve how you can improve the longevity and |
| 1:18:44 | you've also mentioned saliva and more efficient ways |
| 1:18:49 | to uh to get data uh what does that involve what's the future |
| 1:18:56 | of data collection look like yeah for the human biological system right well yeah the the issue with with |
| 1:19:01 | 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 |
| 1:19:06 | 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 |
| 1:19:12 | machine and it'll it'll do that for you but we're not there yet so the intermediate um |
| 1:19:18 | future that that i'm building right now is that you would take a swab of the inside of your mouth which |
| 1:19:24 | is the easiest way to take cells out of your body and just ship them off okay so called a buckle swab |
| 1:19:30 | 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 |
| 1:19:36 | 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 |
| 1:19:43 | you'll swab your cheek stick it back in an envelope send it off and you know a week later you have either a |
| 1:19:48 | doctor's report or a health recommendation and what can you get off a cheek swab well you can get |
| 1:19:55 | anything you can get hormones stress levels stress hormones blood glucose levels you |
| 1:20:00 | can also tell your age reasonably accurately doing that actually quite accurately and those |
| 1:20:06 | clocks cannot just tell you how you're doing over time but can be used to give you |
| 1:20:11 | recommendations to slow that process down because some people sometimes are 10 years older biologically than their |
| 1:20:16 | actual chronic chronological age i mean why does it matter how many times the |
| 1:20:21 | 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 |
| 1:20:28 | 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 |
| 1:20:35 | you are biologically based on what we call the epigenetic clock |
| 1:20:41 | and you might be freaked out you might be happy but either way we can advise you on how to improve the |
| 1:20:47 | trajectory because we know that smoking increases the speed of that clock we also know that fasting and people who |
| 1:20:53 | eat the right foods have a slower clock without that knowledge you're flying blind |
| 1:20:58 | 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 |
| 1:21:04 | non-stop a rapid antigen test so let me say that particular one |
| 1:21:09 | rapid antigen test they've been a source of frustration for me because like everybody should be doing it |
| 1:21:14 | 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 |
| 1:21:20 | to a dollar so just to clarify you're talking about not research you talk about like company stuff |
| 1:21:25 | like actual facing things i i well right the research on bringing the price |
| 1:21:30 | down has occurred in my lab at harvard and then that intellectual property is being licensed and has been licensed out |
| 1:21:36 | to a company yeah that that will be uh consumer-facing so anybody |
| 1:21:41 | for a small amount of money can do this well you got subscriber number one obsessed i think that's a beautiful |
| 1:21:47 | beautiful idea so somebody who maybe i would have been more hesitant about it until a covid |
| 1:21:54 | uh but home tests are super easy i almost wanted to share that data with the world |
| 1:21:59 | like in some way not not the entirety of the data but like some visualization of like how i'm doing |
| 1:22:05 | 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 |
| 1:22:11 | i could share because it inspires others and then you can have a conversation about like |
| 1:22:16 | well what are the hacks that you've tried and have a conversation about like how to improve lifestyle and those kinds |
| 1:22:21 | 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 |
| 1:22:27 | talked about security there but once it's anonymized you can then plot these numbers and i've plotted my |
| 1:22:34 | epigenetic age versus hundreds of other people who have taken this test now and i can tell you where i fit |
| 1:22:40 | relative to others in terms of my biological age and i'm happy to share that with you all because it's pretty low |
| 1:22:47 | you can choose to share it of course not everyone wants to share that but when you go to the doctor first of |
| 1:22:52 | 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 |
| 1:22:58 | but second of all we never know how we're doing relative to others because we all |
| 1:23:03 | 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 |
| 1:23:09 | 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 |
| 1:23:16 | 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 |
| 1:23:21 | white and we're male and we're this age and we do this are we good are we doing the right |
| 1:23:27 | things or the wrong things do we need to fix certain things and this is what the future is it's |
| 1:23:32 | forget about just experimenting and not knowing the result i mean who doesn't experiment and doesn't look at the data |
| 1:23:38 | 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 |
| 1:23:46 | where our doctors can look at that but we can also look at it and they can recommend you know go to |
| 1:23:51 | 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 |
| 1:23:57 | vitamin k2 go for it ridiculous question or perhaps not if |
Extending lifespan
| 1:24:03 | 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 |
| 1:24:09 | terms of how long a person would live like what is the maximum longevity that |
| 1:24:14 | we can achieve through the methods that we have today of uh or are |
| 1:24:20 | developing some of the things we've been talking about and in terms of genetics in terms of |
| 1:24:25 | biology what's is there a number right uh well so it changes all the time |
| 1:24:31 | because technology's changing so quickly i keep revising the number upward uh but i would say that if you do |
| 1:24:38 | the right things during your life and start at an early age let's say 25 we don't want malnutrition starvation |
| 1:24:43 | that's not what i'm talking about but in your 20s start eating the kind of |
| 1:24:48 | diets that i talked about skipping meals in animals that gives you an extra 20 |
| 1:24:54 | to 30 percent we don't know if that's true for humans and that would you know even five percent more would be |
| 1:24:59 | a good a big deal for the planet i think that we should all aim to at |
| 1:25:05 | least reach a century um i i'm i'm a little bit behind i was born too early to benefit |
| 1:25:11 | the most from all of this discovery those of you who are in your twenties you should definitely aim to reach a |
| 1:25:17 | hundred i don't see why not consider this is really important the |
| 1:25:23 | average life span of a human that looks after themselves and but doesn't pay attention |
| 1:25:29 | is about 80 okay japan that's the average age for a male bit higher if you do the right things |
| 1:25:36 | in your life which is eat healthy food don't overeat don't become obese do a bit of exercise get good |
| 1:25:43 | sleep and don't stress that gives you on average 14 extra years that gets you to 94. |
| 1:25:48 | so getting to 100 if you just focus on what i'm talking about it's not a big deal so what's the |
| 1:25:54 | 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 |
| 1:26:02 | of of uh of where we can get to with the types of technologies that i'm talking about |
| 1:26:07 | medicines like i mentioned rapamycin there's one called metformin which is the diabetes drug |
| 1:26:12 | which i take that in combination with these lifestyle changes should get us beyond a hundred |
| 1:26:18 | how long can we ultimately live well there's no maximum limit to human lifespan why can a whale live 300 years |
| 1:26:23 | 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 |
| 1:26:30 | x i think is is full of it there's nothing that i've seen that says biological |
| 1:26:35 | organisms have to die there are trees that live for thousands of years and their biochemistry is pretty close to ours |
Immortality
| 1:26:42 | 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 |
| 1:26:48 | years there's some some sense you could argue |
| 1:26:54 | that there is immortal organisms already living on earth like there's bacteria so |
| 1:26:59 | there's certain there's certain living organisms that in some fundamental way do not |
| 1:27:06 | die because they keep replicating their genetic information they keep like cloning themselves |
| 1:27:13 | is is it the same human if we can somehow persist the human mind |
| 1:27:21 | like copy clone certain aspects and just keep replacing body parts um do you think that's |
| 1:27:28 | another way to achieve immortality to achieve of a prolonged sort of increased longevity is |
| 1:27:34 | to replace the parts that break easily and keep because actually from your theory of um |
| 1:27:41 | aging as a degradation of information it's an information theory view of aging like what is what is the key |
| 1:27:49 | information that makes a human can we persist that information and just replace |
| 1:27:54 | the the trivial parts uh yeah i mean the short answer is yes we're already |
| 1:28:00 | replacing body parts but what makes us human is our brain everything else is is sub-optimal |
| 1:28:06 | except our brain the ability to replace actual neurons is |
| 1:28:12 | really hard right i think it might be easy to upload rather than replace neurons because they're so tight |
| 1:28:19 | it's such a network and just perturbing the system you know it's it's uh it's stretching this cat you |
| 1:28:26 | you change everything once you get in there the problem is um well i guess the solution let me go to |
| 1:28:32 | the solution that's more interesting what we're learning is that if you reverse the age of nerve cells |
| 1:28:37 | 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 |
| 1:28:43 | how to interpret them and function correctly and this is one of the things we're starting in my lab if |
| 1:28:48 | you take an old mouse that has learned something when it was young but forgotten does it get that back and |
| 1:28:54 | all evidence points to that being true so i'd rather go in and rejuvenate the brain as it sits rather than replace |
| 1:29:00 | individual cells which would be really hard what do you think about like efforts like neurolink |
| 1:29:06 | which basically you mentioned uploading are trying to figure out so creating |
| 1:29:12 | brain computer interfaces they're trying to figure out how to communicate with the brain but one of the features that is trying |
| 1:29:18 | to record the human brain more and more accurately do you have hope for that |
| 1:29:25 | to um of course there's uh it will lead to us better understanding |
| 1:29:30 | from a neuroscience perspective the human mind but do you have hope for it increasing longevity in |
| 1:29:36 | terms of how it's used i think that it can help with certain diseases uh but i see at least within our |
| 1:29:42 | 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 |
| 1:29:48 | retina and other parts the visual cortex back here that that's going to be doable in terms |
| 1:29:54 | of longevity maybe we could put something on the hypothalamus and start secreting those hormones and get |
| 1:29:59 | that back ultimately i think it the best way to |
| 1:30:04 | preserve the brain uh is going to be to uh record it but also i think it's going to |
| 1:30:11 | require death unfortunately to then do very detailed scans even |
| 1:30:17 | if you have enough time and money atomic microscopy and rebuild the brain from scratch rebuild from scratch yeah we are |
| 1:30:25 | living more and more in the digital world i wonder if if the scanning is good |
| 1:30:31 | enough for the critical things in terms of memories in terms of the particular quirks of your cognitive processes |
| 1:30:38 | 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 |
| 1:30:44 | it's uh if you're um if you're an exponential type of person |
| 1:30:50 | yeah well let's dream a little here yes the way it would work that i could see it working is so you |
| 1:30:56 | take a single cell slice through your your dead brain and we can now the |
| 1:31:01 | problem the problem with the engineering aspect is that the engineering is the physical aspect of the brain is is |
| 1:31:07 | not even half the problem the problem is which genes are switched on and off this experience that |
| 1:31:13 | we're having here is is altering certain genes in neurons that will be preserved hopefully for for |
| 1:31:20 | a number of decades but you cannot see that with a microscope easily but there are technologies invented |
| 1:31:27 | actually just down the hall in the building i'm at george church invented away his lab invented a way |
| 1:31:33 | to look at which genes are switched on and off not only in a single cell which any lab |
| 1:31:38 | can do these days but in situ where it's situated in the brain so you can say okay |
| 1:31:44 | this nerve cell had these genes switched on and they switched off we can recreate that but just scanning |
| 1:31:50 | 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 |
| 1:31:56 | biology the full details and look at the epigenome and the apogenome too yeah which genes are on and off |
| 1:32:03 | it's just easier to reset the epigenome and get them to work like they just use we're doing that now use the |
| 1:32:08 | hardware already have just figure out how to uh make that hardware last longer right |
| 1:32:14 | ultimately information will be lost even genetic information degrades slowly through mutations so we |
| 1:32:20 | immortality is not achievable through that means though i think we could potentially reset the body hundreds of |
| 1:32:25 | times and live for thousands of years okay so we talked about biology |
Denial of death
| 1:32:31 | let's forgive me but let's talk about philosophy for just a brief moment |
| 1:32:36 | so somebody i've enjoyed reading ernest becker wrote the denial of death there's also |
| 1:32:41 | martin heidegger there's a bunch of philosophers who |
| 1:32:47 | claim that most people live life in denial of death sort of we |
| 1:32:55 | don't fully internalize the idea that we're going to die |
| 1:33:00 | the because if we did as as they say there |
| 1:33:07 | will be a kind of terror of um i mean |
| 1:33:12 | a deep fear of death the fact that we don't know what's like we almost don't know what to do |
| 1:33:21 | with non-existence with disappearing like our the way we draw meaning from life seems |
| 1:33:28 | to be grounded in the fact that we exist and that we some point will not exist is |
| 1:33:33 | terrifying and so we live in an illusion that we're not going to die and we run from that terror |
| 1:33:39 | 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 |
| 1:33:45 | experience it every day when i talk to people we have to live that way although unfortunately |
| 1:33:50 | i can't but for most people it's extremely stressing distressing to think |
| 1:33:56 | about their own mortality we think about it occasionally and if we really thought about it every day |
| 1:34:02 | we'd probably be brought to tears how much we not just miss ourselves but miss our family our friends we are |
| 1:34:10 | all living life forms have evolved to to not want to die and when i mean one biochemically |
| 1:34:16 | genetically physically that yeast cell the cells that i studied at mit |
| 1:34:21 | they were fighting for their lives they didn't think but our brain has evolved the same |
| 1:34:26 | survival aspect of course we don't want to die but the problem for us unfortunately |
| 1:34:32 | it's a curse and a blessing is that we're now conscious we know that we're going to die most species |
| 1:34:38 | that have ever existed don't that's a burden that's a curse and so what i think's happened is |
| 1:34:43 | we've evolved certainly to want to live for a long time perhaps never want to die but the thought about |
| 1:34:50 | dying is so traumatic that there is an innate part of our brains and it's probably |
| 1:34:56 | genetically wired to not think about it i really think that's part of being |
| 1:35:02 | human and it because you know think about tribes that obsessed with longevity every day and |
| 1:35:08 | that were going to die they probably didn't make much technological progress because they were just crying |
| 1:35:13 | in their hearts every day or you know on the savannah so i really think that we've evolved to |
| 1:35:18 | naturally deny aging and it's one of the problems that i face in my career and you know when i speak publicly and |
| 1:35:25 | on social media is that it's shocking people don't want to think about their age but i think it's getting better |
| 1:35:31 | i think my book has helped these tests that we're developing should help people understand it's not a problem to think |
| 1:35:38 | about your long-term health in fact if you don't you're going to reach 80 and really regret it |
Meaning of life without death
| 1:35:45 | and the other side of it so again ernest becker but also victor franklin recommended highly man |
| 1:35:50 | search for meeting uh bernard williams he's a moral philosopher they kind of argue that this knowledge |
| 1:35:58 | of death even if we often don't contemplate it we do at times |
| 1:36:03 | 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 |
| 1:36:11 | able to contemplate our own mortality that gives meaning to life so death |
| 1:36:17 | gives meaning to life is what viktor frankl's argues i would probably argue the same there's |
| 1:36:22 | something about the scarcity of life and contemplating that that makes each moment |
| 1:36:28 | that much sweeter is there something to that i think it's individual in my case it's |
| 1:36:34 | completely wrong i appreciate you saying that i don't get |
| 1:36:40 | 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 |
| 1:36:46 | it that way and even if i would if i thought i was going to live forever i would still be enjoying this moment |
| 1:36:52 | just as much and i bet you would too well that's uh |
| 1:36:58 | i think about that a lot i i think it's very difficult to know i'm almost |
| 1:37:04 | afraid that i wouldn't enjoy it as much if i was immortal i'm almost afraid to want |
| 1:37:09 | to be immortal or to live longer because |
| 1:37:16 | it perhaps is a kind of justification for me to accept that i'm going to die is saying |
| 1:37:22 | 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 |
| 1:37:27 | enjoy just as much of course enjoying life whether you're |
| 1:37:33 | mortal or not takes work like it it requires you to have the right kind of freedom of mind you |
| 1:37:39 | can discover you can focus your mind on the ugliness of life there's plenty of ugly things in this |
| 1:37:46 | world and you can focus on them you can complain whenever like you know if it's raining |
| 1:37:51 | outside you can you can focus on the fact that you have shelter and you enjoy the the |
| 1:37:57 | hell out of it or you can enjoy running in the rain when it's warm and like |
| 1:38:02 | the the beauty of nature just being one with nature or you can just complain this [ __ ] weather again in boston |
| 1:38:08 | and there you see they're always raining or freezing damn it and like uh the the same the same thing with like |
| 1:38:15 | wi-fi going out on airplanes like you can either complain about like |
| 1:38:21 | stupid wi-fi and on jetblue or something or you could say like how incredible it |
| 1:38:27 | 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 |
| 1:38:34 | uh like check email and even watch movies through this while connecting through satellites that |
| 1:38:39 | are flying to space so it's a matter of perspective and perhaps there's an extra level of work required |
| 1:38:44 | when you're immortal because it's easier when you're immortal or live longer to |
| 1:38:50 | uh to be lazy to delay stuff but if you're not you can still derive the same amount of |
| 1:38:55 | joy it's possible it's possible it's definitely possible in my life |
| 1:39:00 | i i went from being the nothing's working to every day is great to wake up to and i i |
| 1:39:06 | think even if you live i think you're gonna live forever you can you can enjoy every day |
| 1:39:12 | what i do is everything's relative we can compare ourselves to our neighbor who has more money |
| 1:39:17 | 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 |
| 1:39:24 | says look i can when i tell my fingers to form a fist they actually do that |
| 1:39:31 | 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 |
| 1:39:36 | object it's a metal cube about an inch by an inch by an inch and i i tell myself not |
| 1:39:41 | not about cubes but about inanimate objects probably once a day i'll say i'm a |
| 1:39:47 | living thing i can think i can move i can eat i am full of energy and there's that leaf or |
| 1:39:52 | this cube here that will never be alive that's what i look at and compare myself |
| 1:39:58 | 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 |
| 1:40:05 | this lump of metal on this table here we are wondrous things in the universe |
| 1:40:10 | and probably the most wondrous things in the universe yeah we're able to deeply appreciate the leaf or the cube |
| 1:40:18 | and deeply appreciate ourselves which is uh it can be a curse but it's mostly a gift |
| 1:40:25 | especially when you're such a beautiful poem now i'm six i'm as clever as clever so i |
| 1:40:32 | think i'll be six now forever and ever that's a good thing to aspire to |
| 1:40:37 | your uh your grandmother was on to something david this is uh incredible conversation i'm a huge fan |
| 1:40:43 | of your work so thank you for wasting your valuable time with me today i really really appreciate |
| 1:40:50 | it this was awesome thank you for having me on lex appreciate it thanks for listening to this conversation with david sinclair and |
| 1:40:56 | thank you to on it clear national instruments simply safe and linode check them out in |
| 1:41:04 | the description to support this podcast and now let me leave you some words from arthur shorpenhauer |
| 1:41:10 | all truth passes through three stages first it is ridiculed second it is |
| 1:41:16 | violently opposed third it is accepted as being self-evident |
| 1:41:22 | thank you for listening and hope to see you next time |
| 1:41:33 | you |