How to Extend Your Lifespan with David Sinclair | IVY Masterclass

all right do you know the comedian run wait right I'm Ron white tonight and and you you have the the fortune of having me with wine in my hands so whatever you ask is gonna give you a big truthful answer all right how do I live longer that's a good question but I don't know if you know me for the red wine story that was about 12 13 years ago or when we found that red wine in particular a molecule in red wine called resveratrol what it would basically make animals resistant to the effects of a Western high-fat diet and live just as long as an animal that was thin and healthy we published that and that that was some of the media that I first was exposed to that was the Barbara Walters interview on 60 minutes but sales of red wine went up 30% yep right so so I've since learned invest in things that are going to go up in price not but that we've come a long way since then a long long way and I'm fortunate you all have a copy of my first book which is a description of really why we should think about our lives very differently most people are going through their lives right now not realizing that they're going to live a lot longer than they think a lot longer we look at our grandparents and sometimes our parents and think okay that's how long we're gonna live but the truth is that our generations and even more so our children's generation and you know we can talk about our grandkids what's going to happen is that we're going to continue to live longer and longer but the real question and what's most important to me is are we going to live healthier because there's no point in keeping the body alive which is what modern quote/unquote medicine is doing if it's going to keep our brains the same age right and that's what we've been doing we haven't been very good at keeping our brains young so my goal is really to first of all understand why do we age how do we slow it down is it reversible and can we keep the whole body younger and I believe we can and that's what I'm gonna tell you about tonight so now I'm actually 75 that that's a joke but I'm in my 50s now so it's it's getting more and more personal but I started off this project when I was four years old I know it's hard to believe but you you'll read about the story that my grandmother who raised me in part she was a very young grandmother she had my father she gave birth to my father when she was fifteen so to me she wasn't a grandmother she was more like a friend and she wasn't just young she wasn't just you know 40s when I was a kid but she was young at heart she was so immature and irresponsible it was excellent and my mother really didn't appreciate that at all but I was raised essentially by my grandmother who taught me a few things in life which is the reason I'm here today talking to you the first was adults screw up everything and she had lived through World War two and the aftermath and she thought wow humans really can do a lot of bad things so she said to you know little four-year-old David you have to do really good things and show humanity the best that they can be stay young six is the youngest the best age it's it's so if you ask my wife I'm definitely still a kid in my mind she's the one that makes sure everything runs on time and the kids actually get to school but it's been great for my career because I'm a scientist and scientists succeed typically if they stay young and why is that helpful well it's not the immaturity and the irresponsibility that's that's helpful it's the curiosity the wonder of life and I've managed to keep that and I struggled to keep it because the world is a scary and sad place many times but what I try to do mice the secret of my success as a scientist to share that with you is the following I try to imagine what life would look like to an alien what I mean by that I mean that if we can get rid of every preconceived idea we've never watched a movie we've never delved into politics there's no tradition and we just looked at humanity from above and said how do they score are we a 1 out of 5 or they are 5 out of 5 I think we're kind of a 2 out of 5 at this point and we can do a lot better and one of the things that aliens would do when they looked at us they would say well great they figured out pi the debt that the the numeral numeral PI to a million decimal places great get a gold star for that they figured out equals mc-squared that's pretty good kind of advancing what else would be good well that they've traveled to a rock that's floating around their planet good stuff guys but they'd say well what about medicine and we'd say well we're tackling this heart disease it's really bad in it and then there's diabetes we've got to solve that and they'd say that's great but do you know what causes all those things we'd say uh I'm not sure what and they'd say aging aging is your problem and we would right now in our civilization we'd say aging isn't that just natural isn't it shouldn't we just deal with that and they said the aliens would say guys and ladies aging is just as natural as cancer and heart disease and Alzheimer's why are you focusing on all those things that kill you while ignoring all the things that cause those things in the first place so my argument is why are we focusing on what causes us to fall off the cliff without even talking about let alone working on in a big way what drives off us to that edge of the cliff in the first place and so my mother she died a few years ago from lung cancer and I'll be the first person to say lung cancer and cancer in general is a great push you to solve cancer but we spend I think it's about five billion dollars a year just on research alone on cancer but cancer is only part of the story if you smoke like my mother did your chance of getting cancer lung cancer goes up by about fivefold which is really bad right so we try not to smoke and there's big government campaigns to try and prevent it but if you go from 20 to 70 your chances of getting lung cancer go up by five hundred fold and nobody's even talking about it so what's the major killer it's aging so my goal with my research at Harvard Medical School which I've been doing at Harvard for 20 years and five years over the road at MIT is to figure out why do we age I mean does any doesn't anyone have a clue why we age does anyone really and do any of you think about it probably not right because even doctors who treat aging the gerontologists they don't think about it either it's as though we're we've evolved to not even think about it and I think the reason is that it's too painful to think about mortality I mean let's do a little experiment and I've never done this before this is off the cuff think about your parents if they're still alive that's great if they're not imagine that they're still with you what would you give for an extra month with with them to be able to talk to them spend time with them show them what you've been doing spend time with your grandkids those those are the important things in life and we we don't even think about our own mortality typically it's really quite painful right to think that one day literally none of this will be around for us and we'll be we'll be out of here that's scary stuff right you got the whole hold on about 100 religions to help us with that but my book is is not a negative message it's not oh let's all freak out because we're going to die it's more let's focus on what's going wrong during aging and try and keep all of us our parents ourselves healthier until 90 or hundred or beyond and the good news is the science which I'll tell you about tonight says that it's not about extending lifespan even though that's the title of the book it's about extending health span so that you don't have to be sick when you're 70 or 80 and I'll show you that it's very possible with things that we can do today with our lives and I I'm quite happy that I heard some of the right things tonight about what you should be doing the other great message and inspiring fact is that only 20% of your life span and health in old age 20% is genetic and we know that because we've studied twins and twins there's always a good bet good twin and a bad twin right and the bad twin who goes in the Sun who smokes who doesn't exercise who eats a lot of food that's when we'll age rapidly not just be sick but but literally you can measure aging now I'll tell you about the clock in our bodies so we know that 80% of our existence and our health is in our own hands that's great that's really my message and one of the reasons I wrote the book is that don't be afraid of aging take action because you really can have a big impact on your own life and spread the word because there's really a lot we can do fairly simple things to live longer and healthier all right so that's let's see if we can get this all right okay so this is a picture of a young person an old person and when I asked you how long do you want to live which I will do think about that I want you to imagine that some of the technologies that I'm going to talk about tonight and the things you can do will actually work okay so you might have an extra five years ten years so my question to you is it's a multiple choice question but you get to get to vote once who of you wants to live just 280 and then and then you know pass away is 80 enough for you you are the first audience who has zero at 80 fantastic what that means is either I've convinced you but I think what more importantly what it says is that you're an audience who's really enjoying life why not why if you love life why would you want it to end of course not if as long as you're healthy and enjoying what you're doing nobody wants to die if I actually told you you're all 110 and that you know imagine we go up to City Hall in Cambridge and there's a summer at the desk and they made a mistake on your birth certificate turns out you're actually 110 you didn't know it do you suddenly want to kill yourself no of course right just being a certain age doesn't mean you want to die it's how you feel how about let's let's pick another number who would like to live beyond a hundred well that's where I'm going all right no no that's okay but you still got a vote and then we'll come back all right well let's jump ahead what about 150 does that sound attractive enough if T okay so in it does to Penn so that's where we're going what about immortality yeah so you must really love what you don't all right so so here's the catch most people and and you're you're a cut above most audience as I speak to I can tell already most people say 80 or 100 that's enough because they've seen what it looks like to get old but because I think I prepped you and I think because you think more deeply than most we're talking about being a hundred and still being able to play tennis and hang out with the great grandkids and live a life like we do today without losing your mind and that's what we're we're talking about with the things that I can tell you today and the technologies that are coming very soon so let's uh let me ask you again okay I'm certain none of you won't have changed your mind about 80 but what about a hundred anybody want to die at a hundred even if you're feeling the same way as you do today it's enough you get you get bored with life out of here okay that's fair enough everyone's choice night yeah living in yeah well so one of the points I make in my book is that we should have the choice to die when we want to as well all right that's just as important to choosing how long you can live so a hundred how about let's go 250 yeah maybe somewhere in between 120 what what what makes you feel that way yeah I I pity your parents well you well I'm gonna say that at 150 you you look and feel the same way you do today and so do all your family and friends so nothing's changed just just the number of candles you have to put on your birthday cake is there a date where you don't want to live anymore [Music] so we can get into the laws of thermodynamics I'm prepared for that psychologically though so here's what I'm trying to get out if you don't feel any different and you've got a great career and you're surrounded by family and friends is there a date when you want to die is it a point in life where you just get bored I've seen every movie I've done everything I wanted to do my bucket list is full I want to die bang is there a date it sounds like yes that's fair that's totally fine that's that some people so what about immortality under these conditions of Continuing nope would you now that's a good question yeah Yeah right do we only enjoy life and have agency because we know that there's an expiry date very Protestant of you yeah no it's it's a fair point but it we don't know what it's like to live without fear of death that's right but I what I've discovered in my lab which most people don't know unless they've read the book is we found that there's a backup hard drive of youth in ourselves in our body that we can tap into and reset the system and we've reached we've reset at once we maybe can reset it a hundred times maybe let's talk about that let's talk about that we've only done it in mice but we can reset a mouse pretty quickly and pretty easily and send their age way back I'll show you how that works exactly so I just got off a plane yesterday from was a bodega Marine Labs I think I'm messing up the name but it is north of LA and I was there collecting jellyfish because we're studying jellyfish in the lab because I think just like you've proposed that the secret of reversing aging continually was solved by jellyfish it was solved by a lot of life-forms trees do it they can spawn new offspring our bodies have forgotten how to do that but what you'll you'll read about hopefully you'll get into the book is that we figured out that there are three genes in the body that if you turn them on again because they could get switched off when we're young we turn them on again in an old animal and probably ourselves I would guess we get to experience what it's like to be a jellyfish let me show you the mouse because the mouse doesn't have to be in water and I promise to tell you the clicker is not working but let's plug it in and see if it works all right this is the only graph I'm going to show you all right but it's a really cool graph it's a graph of the longest-lived countries in the world versus the 19th and 20th century yes see if we can get that to work so this is 1840 so the life expectancy average life expectancy in the best country in the world right which is light blue which is probably your heroes Sweden cool I'm jinxed there we go we'll get there all right so in 1840 the best you could do was in Sweden and you're at 45 years 1840 cholera you could die from a splinter horrible right into the kind of the modern times 1940 right it's still pretty pathetic average life expectancy the best you could do in the world was about 70 years and this is when we expected to retire at 65 and live another five years and drop off that's not the world we live in and it's certainly not going to be the world we live in when we're older and when when we're in our late late retirement but I want to point out two things one is that this is this is very linear right that even though we've had advances in vaccines and and antibiotics and all of the wonderful medicine it's it's almost unbelievable how linear this is and the second thing I want to point out in this slide is that what these little things are you can't read them but these are estimates of the maximum human average lifespan so for instance this study here in 1921 said that that's where we're gonna stop that that'll be the plateau and people won't live longer than that and every time these studies have come out saying we've reached our maximum they've been wrong so that's the good news and we keep breaking it and you can see the predictions that everyone says we're gonna slow down no it's true in the u.s. that we're we're not going up dramatically currently but that's not because of educated people with access to health care it's because there are you know that it's offset by people who are addicted to opioids and other issues not to mention obesity being an epidemic but that's not most of most of the people in this town really and I do get to in in the book I talk about how there's a disparity especially in the u.s. between those who know what to do to be healthy and live longer and those who are trapped in a cycle of where their lifespans are you know basically down here and that's why the u.s. lifespan is what it is but that's the average and not everybody is average most people are not average yeah well it could but we're not we're no longer at the whim of evolution we innovate okay what about this room is natural give me one thing the wood there's a plant cool alright so yeah we probably have a natural maximum yeah yeah there's nothing natural seriously I was a once on a plane with a guy who was flying with me to Tokyo and I told him that we're working on aging and trying to make people live healthier for longer he goes I don't know that doesn't sound natural are you kidding me we're drinking gin and tonics we're texting our partners we're watching movies 10,000 feet above the ground don't give me what's natural so the point is that we can we can engineer our way out of things and we're already way beyond our natural lifespan all right the minute we killed off all the wild animals in this town that's a good start yeah so my understanding of this graph is that this is life expectancy not average lifespans so that it discounts early childhood death but it's a good point which is that initially most of the gains in average lifespan were at the lower end of life and we've basically most of us can expect to live if we're lucky enough to get through our 40s 50s and 60s so we're coming up against the limit which is aging okay so that you know we can we can study childhood diseases a lot and I think that's worthy but most of us now get to be old and that's what the problem is the biggest problem on the planet so right now as of last year there are more people on earth who are over 65 than under the age of five and that's the first time ever in human history and it's only going to continue to widen so our problem as a species is what are we going to do with all the people who are frail and cannot work and have to go to a nursing home that's a lot of money we already spend in the u.s. seventeen percent of our GDP taking care mostly of the sick and the elderly and it's only going to get worse unless we do something about it so we really have two futures one is let's just forget about aging and we'll just deal with a lot of sick people who spend more and more of their % of their lives being looked after or we can say this is a problem let's figure it out and let's fix it which is what we've done for everything that's why we we wear clothes and we were indoors in a heated building so yeah so hopefully I've convinced you at least you've seen my argument that it's natural therefore acceptable that argument should be thrown out the window we've never as a species accepted things that have caused us pain or difficulty just because they're natural I'm also gonna tell you that there's no one solution to aging you might read about it it's not true I'm one of the world's leading scientists in the study of longevity we don't call it anti-aging because that's that's a bad word because a lot of people out there saying I've got your anti-aging treatment what we're trying to figure out is other genes that control the aging process and other things we could do to turn them on in our daily lives and eventually with medicines and they're actually some medicines some things that I take right now which when you go home you can skip to page 304 and read all about that's the cheat sheet but those things we've learned through really hardcore world leading science so you may not know that that there have been at least one you could argue two Nobel prizes awarded for aging research already one was the tell'em the telomeres you know about telomeres the ends of chromosomes how those get extended and the other one is about protein misfolding called motofuji the clearance of these bad proteins those two things led to a Nobel Prize and I'm sure there's going to be more Nobel Prizes awarded for other aspects of Aging all right so this is the anti-aging if you go online you will be completely depressed and why do I say that because you don't know what to believe people are saying take this pill take that pill this pill works David Sinclair says so it's all wrong I don't say any product works but you know that this is the world we live in we have a world of pharmaceuticals which are essentially proven to work and a world of supplements which are not proven to work but there's some some academics like me that it may be treated in a mouse so it looks looks kind of interesting and what's difficult about the world that I'm in is that I'm trying to do the hardcore research and make medicines but every day understandably I'm asked by people well that's great about medicines but I'm getting old right now what can I do now and so I I've written the book which covers both angles what are the medicines that are in the pipeline what are the medicines you could get prescribed right now that would slow aging we think but also what can you do in your daily lives that you don't need a doctor to do I want to bring up antioxidants so you know I hope I don't get sued for saying this but antioxidants have been extremely disappointing in the aging field longevity not anti-aging film why is that because there's a lot of things going wrong in the body besides free radical damage it was a good story it made some sense and all fables are built on things that make sense but doesn't mean they're true an antioxidant so actually have been a Lodge failure in the aging field and we haven't had a lot of success treating animals with antioxidants and making them live healthier or longer and even antioxidants are healthy for you yeah all right all right so we've we figured out that the molecules that some companies are named say are fantastic for you are actually working through a different mechanism which I'll tell you about right oh I definitely believe in in the plant molecules and that's a whole story but I'll get to it and if I don't ask me at the end yep but antioxidants unfortunately not a cure to aging right oh we're all be living 250 at this point orally some of us who are eating a lot of blueberries and drinking pom wonderful every day you know I'm not saying that bad for you but I'm reminding you that that we we know a lot more but people don't know about it yet yeah I'll leave it there but I'll come back so this is what scientists scientists believe are the main causes of Aging these are called the hallmarks of Aging and there are eight or nine depending on which continent you come from and some of these you've probably heard of right they make it into the public's perception of what we work on there is well let's see cellular senescence how many of you have heard of senescence before a few yeah so what this is is that cells will become old and and lose their identity and they'll check out and they'll just sit there and that that would be not so bad if it wasn't for the fact that these senescence cells or sometimes we call them as the zombie cells they start putting out all these other signals in the cell or outside of the cell that make other cells sick so there even though if you don't have a lot of senescence cells in your body even if it's only a few percent they will basically cause the rest of your body to become inflamed and aged as well and we know that mostly from Mouse experiments where you put a few senescence cells a little dab of senescence cells in the animal and the whole animal gets all so they're horrible so we don't want Samba cells we don't want to rather run out of stem cells DNA damage genome instability so that's picture of DNA we've known about for many years telomeres the ends of chromosomes gets shorter and you know it goes on and on and on but here's the point this was 10 years ago and the field of aging research we felt pretty good about ourselves we said yeah we figured this out put a flag in the ground we've done this we figured out what causes aging and everyone with very few exception has started it or don't focus their lab on this one or there you know there's a purple lab and there's a green lab and there's a red lab but I've always believed that you can simplify everything I'm a reductionist and I think eventually we can reduce aging down to a single equation and I can even write it out for you if I had a whiteboard and I'll tell you what that is aging is essentially what's driving all of these things is a loss of information okay we live in an Information Age we know what happens when you lose information we used to lose emails we don't anymore and I'll explain why but information is key and when we're born we have all this great information that we got from our parents and what we what we ate what we absorbed in the womb and how our mother was eating and feeling that's information and what we've discovered in my lab is that over time what's happening to cause all of those things on that pie chart is just one major thing and that's the loss of information in the cell okay so what kind of information I'm glad you asked I'll tell you there are two types of information in biology the one you all know about is DNA genetic information it's a great way to store information in fact you can get information out of a fossil I can go to a mummy and see that mummies do that's a very robust way to store information it's way better than a compact disk or hard drive they wouldn't last thousands of years were they so DNA is a great storage information and the reason it's particularly impressive in terms of the biological system is that it's one of the few things in our body that's digital and we all know digital is better the reason we converted from analog in the first place we don't use cassette tapes anymore for a good reason because analog information sucks anyone who's had you know is old enough to have cassette tapes or record player records knows that you can lose information pretty easily if it's stored in analog but DNA is digital a TCG that's a that's a digital code it's not binary it's core ternary so what is it about the body's information that gets lost over time turns out we used to think it was the digital information that we lost right how many of you I'm sure all of you have heard I won't even ask you we've all heard that mutations drive aging we're losing genetic information as we get older the problem with that is that you can delete a lot of genetic information in animals and they don't age it's also true that very little very few mutations can be found in our our old bodies the smoking gun just isn't there and what happened to the field a few years ago was we had no clue what was driving aging at the fundamental level because the old idea of free radical damage and mutations was out the window there's nothing to replace it with and so what I've proposed in the book and in some recent publications that and some of that are just about to come out as a radical new theory that the other type of information is what we lose over time it's the analog information in the body and that's not very stable at all so what's the analog information it's this green stuff this is the DNA the digital and the packaging of the genome is the analog form of information but we need analog information because the analog system tells the cell which genes to read and without knowing which genes to read a cell is basically a tumor at best or dead we need to have these structures that say read this gene but bundle up all these others who don't read those genes if all cell's read every gene a nerve cell wouldn't be a nerve cell and a skin cell wouldn't be a skin cell you need to be able to tell it only read those 10% of genes and turn off those others and what we found during aging is that these structures that control how the DNA is packaged the analog information which we call the epi genetic information or epigenome is what gets screwed up with time does that make sense it certainly made a lot of sense to the people in my lab but just making sense as I warned you isn't proof of anything right most things that make sense are wrong you know like I won't get into religion but there's a lot of things that we believe that probably are not not true so what what do you do to test this hypothesis okay what do you do you have to say well if I disrupt the analog information if I accelerate that process what should happen well we should get aging we should accelerate that process the converse should be true if I can regain the epigenome the at the analog information we should get younger and that's what we've been doing for 10 years in my lab but most of the world doesn't know about it yet because we haven't published it but it will come out next year so you get a sneak preview and it was also fortunate I was writing a book while we made these discoveries so I said screw it it's gone in the book so for the first time probably since a long time a scientists biggest discovery is in a in a book that you can read about before scientists have actually had a chance to have it published all right so there's that another analogy that I think is appropriate here is a compact disc now when I teach high school students I have to tell them what a compact disc is we used to put music and and movies on these things but it's a it's the best analogy I can give you so our genome is that is the music that's encoded in these ones and zeros as we get older we're getting scratched up so that the music becomes it's skipping and the cell by this analogy is not reading the right songs at the right time and this if this were a cell this cell would not be behaving well it would be losing its identity if it was a nerve cell it might be thinking that it's my like a skin cell liver cell isn't behaving the cardiovascular system is forgetting to how to how to be a cardiovascular system and that's why we get sick as we get older I I believe and all of these symptoms of aging and these diseases that we we try to treat but too late I think it because our cells have lost their ability to read the genes at the right time in the right place and that we essentially had really good evidence for for the last seven years in my lab and I'll show you that data but what if we could remove those scratches would that be amazing what if the cell could now go back and read the right genes and we didn't know that that was possible until recently but turns out as I said there's a backup of these of this original state so we can polish all right I have a movie to show you so one of the things that happens on the chromosome that disrupts the cells identity and the ability to read the genes is a broken chromosome okay wherever you see that flash the chromosome is being broken and when you break a chromosome a cell gets really nervous because it it's actually the worst thing you can do to a cell because if a cell doesn't repair a chromosome it'll it'll die or it'll become a tumor you got to fix it no question you cannot live with broken chromosomes so what I showed you in that video those balls are proteins in the cell that we've discovered when I was over at MIT and now and more recently in my lab these proteins are what we call longevity enzymes they're encoded by longevity genes and when we turn them on the animals very healthy they're great we have mice that live longer and we think in our bodies they keep us young but they unfortunately they have two functions the first function is really important it's to maintain the structure of of the the epigenome to keep us young so that's great when when we're young these proteins are in the right place they're sitting on the right genes and so the genes that should be on Iran and the genes that should be offer off but as I showed you in this video their other role is that they get distracted by broken DNA if you go out in the Sun and you get sunburned you broke a lot of DNA unfortunately so these proteins are moving from where they should be in a panic to try and repair the DNA there's a reason for that I think that it's that they're moving because they're they're telling the cell there's an emergency you got to fight you got to survive but if you keep doing that as I showed so this is an acceleration of of what I think happens during aging let's have a look again these proteins are perfect perfectly aligned then they get distracted by the break they go back to where they came from they go to the break they go back to where they came from they go to the break whoops didn't go back whoops didn't go back so this is aging I believe and we can test this we can create this in the lab in an animal and ask what happens and we've done that that's taken us ten years I'll tell you a little bit about these guys on the video lose what I said so these genes are called sirtuins that we've worked on and it's pretty interesting when you think about why they're called sirtuins and you probably don't know the first three letters of sirtuin is si R and that stands for silent which means turn the jeans off silence them information regulator okay so it in the name of these genes has been the answer all along I believe information regulation is the key to longevity but breaking DNA is one of the things they accelerates aging because it distracts them and eventually like opening andrey gifting a present a thousand times it's going to be pretty ugly by that point but the question that I've been asking myself in the lab for the last few years is is there a treatment you can give to a cell or an old animal or eventually an old person that can go from there back to frame one and get them to go back to where they came from so the cell reads the right genes to be a neuron a young healthy neuron or a young skin cell and I think we found that so here's the experiment in the lab where we scratched the DVD scratched the CD this is a control mouse that's at this point it would be 16 months old and we took one of its brothers or sisters and we scratches DVD what we actually did was we cut the chromosome in a few places distracted the proteins and they ended up getting older okay and you might say well that looks like a sick Mouse but David how how do you know it's old well it certainly looks old it's got grey hair it's got wrinkled skin that has lost its hair hair loss mice lose their hair when they get older but that's not proof of anything you know anybody can create a mouse looking like this you know maybe if you microwave a mouse they look like that I don't know don't do that at home I'm joking so what we did was we we studied these mice for years to find out how much do they look like real aging and they look like real aging we've sent mice to hundreds of researchers around the world two experts on the kidney on the skin on the bone on the eye sight on the hearing and they look at the tissues and they say yeah that's old and I have to say they're not old we've given them aging but there's really been a breakthrough in the last few years in our ability to really know if that Mouse is older or not not just by looking at it but by measuring its age and we no longer in my field count age buy candles we can actually count the age biologically because there's a clock that ticks over in mice in whales in bats and in our own body which we can measure in fact if I took your blood back to my lab within a few days and you know a fair bit of money I could tell you exactly how old you are biologically and predict within a matter of months when you're going to die using this clock but don't freak out because we can we can change the trajectory we can slow it down so here's the clock this is the DNA right there's the the a C T C so C chemicals in DNA the cytosines they get modified by a chemical called a methyl and a methyl is just carbon hi in hydrogen Argent's nothing spectacular but it's like a it's like crust on well I think it's probably better analogy would be the plaque on your teeth it's accumulating and it does so with very predictable way over time in our lifetime so I can measure your methylation pattern with a DNA sequencer for a few hundred bucks and I could say you're older or younger for your age by this much and we know that if you smoke if you don't exercise if you eat the wrong things you will be older than the average human and vice versa right so this is a new world and so we could do with these mice because we could measure their actual biological age and what you can see from this okay I lied I have another graph but it's not a very complicated one obviously that the one that looks old is older based on this objective measure it's called the DNA methylation clock it's also sometimes called the horvath clock named after my friend and colleague Steven Horvath who actually helped us with this study now I'm gonna tell you something up you're a smart bunch so if you tell you something really interesting but a little bit technical so stick with me there are enzymes that remove the plaque off your DNA called tetes and they're very important when we're young that they're what allows a nerve cell to become a nerve cell and the skin cells of the skin so and I think a jellyfish to regenerate ok these are on when we're young but they you don't want these genes on when you're old it's not a good thing if they're deregulated but it is possible to remove these and so I'll get back to that because it's I think it's part of the understanding of how we can remove those scratches on the CD and reverse aging so here's where things get really interesting can we take that older Mouse and make it young again if we're right about this we should be able to remove those methyl DNA plaques and it might actually not just make them else appear younger in the lab when you read it but maybe it would actually behave like it was young that was the idea so how do you do that how do you get the clock to go backwards well I'll tell you that but first of all I wanted to tell you about why we chose the nervous system to regenerate to reverse aging in because we could have chosen the skin could have chosen the liver to reverse aging but nerve cells become old very quickly as soon as we're you know 3 years old if we damage our eye or we break our back our spine we're not gonna walk again well they're not going to see again we know that right it's because nerve cells become old very quickly and they don't act like they were when we were embryos and so this shows an embryonic nerve growing in the dish that's great but as well as we turn into adults if you put one of our nerves in a dish it'll just sit there it'll try its best to try and grow but it really won't grow very well so we thought what if you could take adult nerve cells damage them or even just old nerve cells in the eye and turn their age back to when they were young would they grow and function like they were young again so how did we decide to do that well there was a nobel prize awarded to Shinya Yamanaka from japan for the discovery that there are a set of four genes called the Yamanaka factors that can take an adult cell and turn it into a stem cell so quite simply any high school student could take one of your skin cells in your mouth take it back to my lab or even to the high school lab put in these four genes from Yamanaka which we call OS k and M for short and those cells many of them would become stem cells not just normal stem cells but pluripotent stem cells meaning they could become any type you want we could regrow we could grow a little mini rain in the dish you can now do that it's pretty freaky we'll grow your own mini brain in the dish I don't think they conscious thank goodness but we could build any tissue and that that was well work well worthy of a Nobel Prize right so we wondered could we use some aspect of this discovery to reverse aging so we don't want to take them all the way back to being an embryo Oh to a stem-cell you know if we did that we'd all end up with the world's biggest tumors in our bodies we wanted to know if we could do partial reversal and just take off the right methyls pick off just the right plaque on the teeth without taking all your teeth off which is what Yamanaka did so we didn't know if it would work we had some clue because there's a scientist at the Salk Institute that a couple of years ago showed that if you turn on all four of these genes in a mouse it lives forty percent longer but that but that sounds great until I tell you that every three days if they didn't stop the treatment the mice would die so that I think he may get the Nobel Prize with his discovery but it wasn't perfect because those poor mice were hit with these factors and they would almost die and then they'd let them recover for another five days and they'd hit them again this is not going to be a medicine any time soon but it sure is an interesting proof of principle that you can turn on these things and make an animal live longer now it was a short lived Mouse so we still have to show that this happens in a regular Mouse but I'll show you what happens in regular mice when you when you put these factors in right so what I'm showing you for the first time is what it was like to make a discovery of a lifetime this was the discovery of my lifetime these are conversations with my student Ryan who made this discovery he put the Yamanaka factors not all four of them he found that three were safe and effective the you know the one at the end to M Mik he left that off because that causes cancer that's known to be a problem but osk put into the back of the eye regenerated the the optic nerve in these mice and so what you're seeing are pictures for the first time that he was sending me of regenerating optic nerves in mice so we had damaged the back of the eye and here we have it the regrowth of something that should has no business we growing in an adult mouse but it's it was you know one of those things where you know we're kind of celebrating that we've we've made a big discovery and I mention it also because when you read the book you'll get a sense of what it was like to experience such a discovery so this is it this is a regular optic nerve that's been damaged it's been pinched and the nerves have died off towards the brain so the brain is out that way and the eye is over here and this mouse has lost a lot of its notes and it's never gonna see again but in this mouse in the in the mouse will show you down here we've reprogrammed its eye to be young again we've put those three Yamanaka factors in turn them on with just an antibiotic called doxycycline now it doesn't have to be an antibiotic sometimes people say what's so good about the antibiotic we've just engineered the system so that the antibiotic is the switch so that we can turn it on and off it's an easy way you just give the mice an injection of antibiotic or put it in their water supply so if we ever have a drug like this it may be that we get treated with the the virus which is the delivery vehicle and then we take an antibiotic to turn it on and off at will so we get reset multiple times anyway look let me show you this but this was the result that most of the nerves here at survived the problem and they started to grow towards the brain we don't know how they know where the brain is they're not growing up that way they're growing towards the brain that's a mystery but then we did a really cool experiment which was if it can make these damaged neurons survive what about if we give it to just regular healthy but old mice what happens to their vision and I don't know about you but you know I'm now in my 50s now starting to become like old mice we lose our ability to see so here's an experiment and I need to give credit to the lab of Bruce and Meredith Cassandra they are at a Massiah near here in Boston and what they do is they ignore ignore the feces this is irrelevant to the experiment I think if if we were handled by giant things we'd be pretty upset too but anyway what they're doing is so he's standing on the platform and this mouse is a year old so those mice actually have become blind and you we know this because when these these lines move they don't watch the lines it's called the Optimo door response so I've had played us for you you'll see that it's not moving its head it's really not not looking anywhere and we can videotape this for from you know half an hour it's not gonna see the lines but you know if we see moving lines we're gonna move our head that's just the natural response so we took myself the same age we gave them a virus that carried the three genes into the eye and that virus infected the nerves at the back of the eye in the retina and they sat there until we gave them the anti bio antibiotic doxycycline to turn on those genes three weeks later after reprogramming their eyes and making them young again and by the way we've measured the age of the eye they do get younger based on the clock the question was does it work or does the clock change but that's just like a clock on the wall you don't really go back in time if you move the hands or if you move the hands because time really go backwards so this was a really good experiment and it was a really good day for Bruce so what Bruce called me about and we get this started so it was 10:00 p.m. at night it was about a year ago and he calls me and he says I'm sorry it's late but I have to tell you we just had a really amazing result and this was the video that he sent me for the first time in history we've got mice that have been cured of blindness that's a mouse they can see and we've done this on dozens of mice this isn't just a fluke every Mouse that gives our treatment gets their vision back and we can measure the the neuronal activity at the back of the eye and we can see that those nerves before the treatment have no electrical activity but after reprogramming them we get the blips back they work again and we can read the pattern of genes which are switched on and off and genes that went off during aging come back on with treatment and genes that went on by accident the scratches come back to normal so we're truly resetting the epigenome so that cells can be young again and mice that shouldn't be seeing you can see again and we've done this also in glaucoma most people have somebody they know friends or family with glaucoma pressure in the eye damaging the retina we've tested mice with that disease and we can restore their vision as well so our first drug if all goes well will be a drug to treat and restore vision in glaucoma patients all right I'm now going to switch to more of a practical thing because we're not likely to be treated with a virus anytime soon it might happen in our lifetimes let's hope we're working on pills as well that can reset cells so it'll be easier than gene therapy but I'm going to talk about some take-home messages for all all of you because I'm asked this every day hundreds of emails what can I do now all right don't show me my show me what I can do and these this is a cheat sheet there's more of it in the book page 304 and I'm gonna go into each of these in detail in a second but the summary is our three meals a day that's that's craziness I really don't think we were we've evolved III three full meals a day certainly not when we're over the age of say 30 so I've started to I've always skipped breakfast I'm sorry to skip lunch when I can and I'm not too stressed so that that sounds pretty brutal right but if you drink coffee tea is fine you can actually be hungry and it's it's not so bad lose your breath you want to yeah I do I do I'll tell you why I'll come back to it yep yep so lose your breath you want to get on a treadmill or walk up some stairs just move get a standing desk our lifestyles today are just atrocious for particularly this region right where atrophying around here I know you're thinking now our muscles our muscles are atrophied most human beings these days in Western in the Western world in that developed well we we have we end up cramping up here our muscles are pathetic it's it's amazing we can even stand upright after sitting for so long so there are exercises that that that I do that I'll highly recommend because every 19 minutes someone in America will fall over and die from it and mostly the elderly of course but if you've got the strength in your hips and a flexibility you're less likely to die from a fall and so the the kind of exercise I I do are I focus on our hip hinge exerciser I'll talk about that a second I think we need feedback because everyone gives up on diets if they don't see it working or they don't know if it's working same with supplements same with sleep so what I'm recommending from what I do with my life is that I I look for feedback you can't change what you don't measure basically and so for over 12 years now I've been measuring various aspects of my life it used to be crazy to measure yourself with blood tests and and other things you know people would say David you're too worried about stuff but actually we now live in a world where it's very easy to monitor things for a few hundred bucks you can get one of these anyone has an aura ring on them they're great I do recommend these I don't only need this company so I can tell you they're great this will measure your heart rate your temperature your movement and be a very good feedback about how you sleeping so if you're wondering why do I feel terrible in the morning this will tell you exactly what happened and for instance you can look at your heart rate and on a bad note my heart rate will stay high and then drop down about 5:00 a.m. and that's if I drink more than a glass of alcohol and I have a heavy meal with a steak so I've learnt to try to avoid those things if I want to have a decent day the next day but if you don't measure it you don't get the feedback the other thing that I do is I have a patch under here okay it's becoming more and more common for non diabetics to to measure their blood sugar levels so blood sugar is a very good predictor of your longevity the higher the worse it is of course you can become diabetic but even without being diabetic it's still bad so for the last couple of months I've stuck a patch on here there's a tiny little needle it doesn't know it you stick it on there and so on my phone I can scan it and I can tell you what my blood sugar is I wasn't going to do this but let's try so it's called the Libra link and let's try so it says ready to scan anyone have has seen one of these before okay so I stick this here and that's my blood sugar so I'm it's in the Green Zone I'm happy you can see that lunch caused can you see the grass lunch caused a big spike the food that I ate earlier good to go it says it's as good as a glucose monitor so it's it most diabetics are moving away from a finger prick now to just putting one of these on oh yeah yeah it's been in Europe for many many years in the u.s. about two years but I do it also because I want to be a role model I want to be on the forefront of this stuff but I've learned a lot of things that I didn't realize and I've also become much more aware of what I stick in my mouth you know like most of us I would just shove stuff in my mouth and forget about it right this was a trash can but if you see it on your phone you know then you're thinking about what's going in and that that alone is fantastic makes you much more cognizant about what you eat and as I mentioned what you what you do for sleep so measure it yeah I never take it out it's stuck there in showers in saunas in swimming yeah it doesn't come off unless you rip it off it's stuck there that's great for two weeks well you can get one from every pharmacy it's just that you need a doctor to write your prescription so if you this one isn't in the book because it's I've only been doing it for a little while but libro link there are a couple of brands Libre link yeah yeah I mean email me if if you want ah so I honestly I don't have any expectations but I do know that people who follow these type of recommendations live an average of 14 years longer than those who don't all right hormesis did I get through all of those points oh we got through sleep and this is BP content I think being meditative is good my rule in life is don't lie because it's just too stressful you got to live life being happy with who you are so I think that's the those are the things hormesis is what doesn't kill you makes you stronger unfortunately we do have to push our bodies or they become complacent and what we've learned through my labs research and others is that these longevity genes these sirtuins they're only activated hyper activated when your body thinks that it's going to die it doesn't mean you have to go to the brink of death but you do need to get out of the chair you do need to be hungry you do need to sometimes have fewer approached amounts of protein because that's what's which is on these defensive genes and it's worse if you become obese and it's worse as you get older their activity goes down and down and down until basically you're at the whim of entropy second law of thermodynamics you're toast but we can turn on our body's natural defenses and the way to do that is is basically give yourself a little bit of adversity that may feel uncomfortable sure being out of breath is not great being cold and in a sauna not that comfortable but what it does is it triggers these defensive responses if you go too much of course that you freeze or you burn or you starve you're not going to live longer but a little bit goes a long way and we know this from many studies even plants respond to hormesis you spray herbicide on a plant a little bit and it will grow better because it turns on these defenses and we didn't know these defenses existed until just about 20 years ago so I'll get to the antioxidants because that's an important point [Music] well calorie restriction which is the the old full term for friends meant and fasting is known to actually speed up metabolism it's act it actually what happens is your body goes into this defensive state when it's really hungry for prolonged periods of hunger maybe not missing a snack but for a day or two what happens is the body starts to burn energy so it'll deplete the fat and it'll rev up your mitochondria so mitochondria the battery packs the power packs of the cell animals that are hungry have more of those than less so actually you burn more when you're hungry it's it's interesting we always thought you became tired and lethargic it's not true and what we think is going on is that the body thinks that it's under threat and it gives you more energy to survive so that's repair your body have more energy to go find food run away from a saber-toothed tiger that might be attacking you but unfortunately modern life all of the the companies whose job is to to make us feel better have done a great job of making us feel better we feel great at the expense of our longevity no there isn't unfortunately you've got to feel it yeah well this will tell you that you're hungry but you don't need that to tell you that no unfortunately there isn't that would be amazing that we should work on there might be a patch that senses things in the blood that can see when things are perfect because it right to get this right we don't know the perfectness the things I told you are my best estimate based on the science and personal experience and epidemiological but the question is if you exercise a lot do you then take the supplement or should you be hungry on the days you don't exercise we don't know the combinations yet so we have to figure that out yeah yeah it's it's complex we're just at the point of understanding what works but not necessarily in combination alright so this is where things get scientific and where I bring in the free radical stuff these are the three main fences that you can turn on in your body to live longer this or two ends are the ones that we work on and they require a molecule called nad to work those enzymes there are seven I mentioned in the body so you can turn them on a few ways you can raise your nad levels by exercising being hungry or taking molecules that raise nad the one that I'm taking page 304 is called nmn not to be confused with M&Ms do not well you can eat M&Ms who just won't live longer and might be 66 is a drug that we're developing for diseases such as frailty there are what are called the accelerators these are the fuel these the accelerators we call these sirtuin activating compounds whereas Verrill the red wine molecule is a certain one activator so that's why when we gave this molecule to mice they were resistant to obesity because the the mice the bodies of the mice thought that they were hungry but they were exercised but they weren't we just tricked them using the red wine molecule but we've made some much better molecules we actually made 14,000 versions since for his very trial one of these has gone into humans and actually was in a small group of people effective in psoriasis which is in an inflammatory skin condition so you know we've come a long way we know if we feed these molecules to mice they live longer this one even works on mice the synthetic one so that the sirtuins again exercise being hungry we'll turn these on nad boosters we'll turn them on NPK that's the middle leg to the stool this is the one that metformin will activate metformin is a drug for type 2 diabetes it's probably used by at least 50 million people around the world probably more it's relatively safe as drugs go the worst complaint typically is an upset stomach which you can usually mitigate with food or a coated pill and it turns on this pathway which is combining with the sirtuins these are talking to each other this evolved to sense the levels of energy in the body and when you didn't have enough energy in the body let's say you are really hungry that would turn on so these are protected pathways the last one the third major one is called mTOR which was discovered by David Sabatini at MIT and it senses how much protein you're taking in and when you have low amounts of protein it will defend your body because it thinks that you're running out of food so these are all hormesis sensors bad stuff happening these genes get turned on and they protect you from disease and aging so what do you want to do you want to not overload yourself with a ton of protein so carnivores I'm sorry it doesn't it's not backed up by the data because you're not going to invoke this guy here mTOR doesn't mean you you have to avoid meat completely but it does mean that I think constantly eating me isn't the right thing to do besides what I like about eating vegetables you can need a lot more of them so you're not hungry this one you can activate by actually not eating as much food regularly eat less often you've got less glucose as you can tell and monitoring that and then this one exercise also being hungry and you can boost your nad with a pill now do we know this is all gonna make us live 30 years longer no that's why I showed you the slide that you know we don't know if this is true or not but it's it's been basically done in in hundreds of labs there's thousands of scientific papers and it's all we've got right now you know those of us who were born in the 20th century wasn't our fault you know probably be better to be born now if you wanted the best of medicine but we have to go with what we've got and this is the best we've got right now based on all the science that we've got I take it and I'm not diabetic I'm not waiting around till I get diabetic my father is taking that for he's borderline diabetic yeah you do so type two diabetics right so that the data as as you'll read in the book is really compelling type two diabetics that go on metformin people have monitored there are other rates of diseases what happens to the rate of heart or frequency of heart disease Alzheimer's frailty and cancer and some cancers are reduced by 40% by this one medicine and those type two diabetics are more are healthier than people that don't even have diabetes and that's in one hundred over a hundred thousand patients so it I take five hundred in the morning and five hundred and night if I yeah so typical debate would take two grams which is that what you recommend for your patients so I take half that and my father takes double that yeah right so there were the Blut there are the Blue Zones where people are known to typically live a long time and one of those places is Okinawa the island of Okinawa in Japan and they do all the right things they're mostly plant-based they have a little bit of protein you need protein so they have a bit of fish but mostly it's plants they're very active so they're exercising a lot raising their nad and they only eat till they're 70% full and they stop that's their habit and they're not exposed to Western hamburger type food but the Okinawans who move to Hawaii they don't live long it's definitely what they're doing as a lifestyle so yeah you you it this all makes sense that we've got this convergence of people who study lifestyle and have said these things make you live longer and those of us who have studied yeast cells and worms and flies and mice and we've come to the same conclusion that there are genes that protect us so what about food oh I'll go quickly because I'm sure you got questions I think eating three meals a day is not the right thing I mentioned that earlier but if you are hungry in the morning by all means have breakfast but try to find a meal that you can go without for me it's breakfast and I actually know that now because I've measured my glucose levels and my body starts to produce a lot of sugar just as I wake up not everybody but some people I sent my data when it first happened I said what's happening I'm glucose overloaded in my body and I'm not eating anything so I sent him a picture of that graph and he said either your liver is making glucose you're one of the people that does that or you've just had sex so I said does it count if you dream about it anyway so it's obvious that that my body's making glucose so I don't need to eat breakfast I've never felt hungry at breakfast so for me to have breakfast on top of my body making sugar makes no sense at all I often miss lunch because I'm so busy today I had a vegetable soup just because I was stressed out but that's my lifestyle I eat normal dinner if anything I eat too much at dinner but I haven't I really like that I do drink red wine one glass of wine today is not going to hurt anybody except for the calories but still worth it in my view how much red wine would you need to drink to be like these mice that live longer the bad news is that you'd need to drink about 300-400 glasses a day so don't do that yeah well some people think that's really good news but the the take-home message is that I think that taking or drinking a glass of red wine for 30 years can have cumulative effects and it's not just resveratrol it's in red wine there are other molecules that are beneficial as well so probably the combination is helpful and very long-lived people often admit to drinking red wine more than more than the rest why I'm not sure why they choose 200 but why is red one better oh that's that's easy to answer yeah because they're skins like the skins have the resveratrol and pulls it out with the alcohol actually most of it is in the in the actual stem but we throw that away in terms of supplements I have a newsletter if you want to subscribe I write about this stuff you can sign up on my on the website it's called lifespan book calm but often people say well where do I get where is very tall if it's not red wine and I have to be careful because I am a professor at Harvard Medical School I'm not a supplement maker I'm not a supplement seller and I don't recommend supplements but I think it's unfair for me to say this is what the science says you're on your own that's not fair either so what I can say is that there are companies that make resveratrol most of them are fine they're look for the really pure ones if you're gonna try it you can get 98% pure or 100% pure resveratrol and that that should be fine I would just recommend don't keep it out in the light I store mine in the fridge I store all all that my supplements in the fridge particularly those nad boosters the nmn that i mentioned it's a little-known fact but it's actually quite unstable if you keep it on the shelf for long for over a few months but yeah so that I can't mention companies unless you grab me on the side whatever but there are a lot of legitimate companies that are making pure resveratrol it doesn't come from red wine they purify it from Japanese knotweed which is everywhere it's on the on the roads here on the side of the road here in in Boston alright so that's food we can get into more things about food later what about the antioxidant i'll i'll tell you about that nope I'll tell you in a minute I've got a few more things what to do move walk everybody says this but it's really really true but it's Malta more important to lose your breath becoming hypoxic will turn on this or to us yes what's wrong with it well so what we think is that when your body has low blood sugar it will turn on those pathways now if you're eating a snack which probably has sugar in it or carbohydrate you'll you'll basically stop your body from turning on the defense's yeah so think of your body as something that only protects itself when it needs to and when it doesn't need to it puts on fat instead for a rainy day which never comes so what we want to do is to do the opposite which is be hungry and in those periods of hunger your body will actually be repairing itself yeah unfortunately at the recommendation from nutritionists which I disagree with is that you should never feel hungry lots of little snacks throughout the day which is based on the idea that you don't want to hurt your pancreas but actually being hungry if you're not sick is very helpful yeah now I skip a meal or two a day there are some people who go for three days and some people who go for a week without eating and I would do that if I could it's pretty painful though has anyone tried intermittent fasting yeah is it ok can you do it yeah not a weeknight yeah it's hard I mean we want to be full we don't want to be hungry it does so there's a dr. Peter a TIA have you heard of him he's an expert in New York he does week and I don't know how he can do that probably because three million people are watching him he does a week fast every quarter yeah he does intermittent fasting but he's he's using his body as an experiment so he's mixing it up sometimes he'll just go keto sometimes he'll do protein and he's monitoring with finger pricks what's happening to him so of course he has one of these but he's also got you know he can measure he toes in your blood yeah yeah so he's done all that and he's he's trying to come up with the right algorithm of what the right combination is because it if we waited for clinical trials we'll all be dead it's it's expensive and slow so there are these people on the frontier I'm kind of on the frontier but he's one of the major ones he's really pushing it so that that's food if you want we can come back this is the the hip exercises that I like to do it's you don't want to just bend your back you've got to keep it straight like a rod and you stick your butt out and then you lift dumbbells like that it's it's pretty annoying but it's very good what happened to me writing this book was that I end up with a permanent cramp in my butt the piriformis muscle which is that one there was seized up and I couldn't walk it was permanently painful and these exercises were the only thing that fixed me and that's apparently very common with our modern lifestyles and I think it's gonna be great when I get older that I'll have full movement and back exercises too so you don't end up with kyphosis like my mother who was around like that what else can you do well this is one of the enjoyable things actually I really do like to sauna and when I was writing the book my editor said what about cold therapy what about that's not true that doesn't work how can that possibly work but I researched it and it turns out there's good evidence that saunas are good for you and increasing evidence that cold plunges are also good for you and a lot of the evidence is written into the book so in the back you'll find there's a lot of endnotes references that you can look up a lot of people read the book two or three times because it's got a lot of information but I do this every weekend with my son as we were talking about before and it's bonding with my 12 year old son it's good for the both of us and in especially in winter it's nothing better than going through this and feeling refreshed like you've just been out at the beach so I spent about 15 minutes in the sauna it's been found that people who do that have lower rates of cardiovascular disease and for example though I do point out that one caveat with that those studies that I cite is that if you're in hospital or you're in the nursing home you're probably not going to go to the gym or to the sauna but that's a caveat I think it's probably working to turn on those longevity genes now cold plunges this is all the rage narrow you can go cryotherapy ice man half is a superstar on the Internet some of the research that we've done is actually showing that cold therapy is good it turns on some of the sirtuins the sirtuin genes number three produces an enzyme that protects the mitochondria free radical damage so when you're revving up metabolism by being cold you're actually helping the cell rid itself of free radicals but you're also building up what's called brown fat and if you haven't heard of brown fat it's because it's a relatively new discovery so babies have a lot of brown fat and beige fat but we thought that adults didn't have brown fat but it turns out we do and the colder we are and the more cold we are when we walk outside the more brown fat we'll have because itself thermogenic our heat producing fat and it's very healthy to have it so I I spend more time the cold these days than I want to and Boston's a pretty good place to be cold the other thing that I'd learned in terms of a bio hack is don't always bundle up and the best place to lose weight and to jet to burn energy is while you sleep super easy just don't have such thick covers on your bed have a sheet I mean don't shiver you got to get a good night's sleep but being a little cold has actually really been helpful to me and I think I'm burning off you know a few hundred cows maybe at least a hundred calories just by having to be a little cool at night so that's an easy easy life hack this one's a little harder we jump my son and I we jump from the sauna into a four degrees Celsius Celsius water bath which feels extremely painful does anyone do ice plunges cold plunge tell you what if it doesn't make me live longer it's it sure does make me feel grateful to be alive my son actually Benjamin he's going for the world record at least his own record I can spend a minute before my body aches and he's in there for 15 minutes what's the problem dad I don't know he was born in New England that's why all right metformin we've covered so I won't go into too much detail you do need a prescription unless you go to Bangkok or somewhere where you can just buy it in a pharmacy it comes from a plant that you find throughout Europe it's just a weed it's a version of a weed molecule called dog wanted quantity one I'd and metformin works does multiple things remember I said it it's important to have mTOR modulated it does that it controls your glucose at Laura's it that's why you're prescribing it but it also has anti-inflammatory action it inhibits DNA damage prevents radicals it stops cancer so it's a remarkable molecule now it wasn't developed to be an anti-aging drug oops I should say longevity molecule but it sure looks like it is one so that's your best bet I think besides all the other things in life that you can do now you might say well gosh how am I gonna get it I don't have diabetes yet I'm gonna have to gonna have to talk to my doctor about that so more and more doctors are learning about this the sales of prescriptions from that Foreman have gone up 20% in the last few years and I brilliant I didn't even have a doctor that gives me metformin though I anyway it's it's a it I'm not recommending it but I'm telling you that the future is here now and there are options all right this is the one I've been wanting to get to because it gets back to antioxidants everybody that I talked to thinks that red wines good for you and blueberries a good view because of antioxidants it's what we've been taught it's a huge marketing campaign and it makes sense the only problem is it's not true the major benefits of resveratrol are not its antioxidant properties it's actually not a very good antioxidant in the first place a lot better ones what it is this chemical here resveratrol it's actually sensed by our body I believe our bodies have evolved to sense the plant world and what we eat is turning on our defenses so why would the body respond to plant molecules besides food well if you're running out of food let's say your crops are dehydrated or the berries that you're picking are have a terrible infestation of caterpillars we can see that but for most of the evolution of animals they didn't have much of a brain they couldn't tell that time was were going to get tough so they needed a way to sense when food was going to be scarce and the best way was to sense the chemicals of plants when they're stressed so what is resveratrol it's actually a plant stress Survival molecule when plants are dehydrated or hit with ultraviolet light too much Sun infected by fungus they make a ton of resveratrol because they're trying to turn on their so2 and survival defences plants have sirtuins right and I think we've evolved to sense that and we've just lucked out that we produce a product that concentrates it and preserves it keeps it away from light keeps it cool and keeps out the oxygen pretty good luck tastes good too but it's also healthy and most of the longest-lived people in the world drink this stuff so that's probably good but we can do better we can make molecules that are a thousand times more effective than resveratrol this is not an antioxidant but it does the same thing as resveratrol because it activates the sirt1 enzyme to defend the body what is sort one do remember I said that it's moving around trying to repair DNA and protect the genome and and stop the scratches I think that by drinking these these molecules and giving those enzymes more activity we're actually keeping the cell from becoming scratched and we know it works in a very accurate way these molecules bind to the blue region of the enzyme so an enzyme it's just a protein that's doing reactions in the cell this end this enzyme will go and tell this gene to be off and while leaving the other one on right remember it's a silent information regulator what it does is remember the original slide where I showed the DNA and then there was that green blob but that green blob is a histone and that's what wraps up the DNA and if you're observant you would have seen that that green thing had little tails swimming off it those are called histone tails and what this enzyme does is that it controls the chemicals that attach to those tails telling a gene to be silent or a gene to be switched on and when you don't have enough of this enzyme around you're old you're not drinking or eating the right things your genes will come on when they shouldn't and that's aging and so it works by binding here these molecules bind here and the enzyme does this and when it's in this act in position it's much more active and it does its job quicker all right we're almost done this is the nmn the nad booster these are the crystals of it that we're turning into a drug and this this molecule when you feed it to mice that are old they can run in some cases twice as far at least 50% further we had some ice that outran the young mice and one actually ran over three kilometers and the treadmill stopped we have little treadmills in the lab and the treadmill stopped and and my postdoc in the lab called me up and said we've got a problem the treadmills broken the experiments screwed up and it turns out it was just that the software was never written for a mouse to run that far so we had to rewrite software so that's we're hoping that in clinical trials we'll see that we can treat a variety of diseases I mentioned frailty but it could be a whole bunch of things related to aging that we end up treating it's in clinical trials we've tested it for two years in people it seems to be very safe I apologize for black mice on a black treadmill there's the mouse there's the mouse you see it can you see a tail so that's the one on Anna man and that's the one that didn't get any we just put in their drinking water they drink it for a few weeks and four weeks and they become fit so why are they running further you might ask well they have more energy but they also have more blood flow it's as though they've been exercising because that's what happens when you exercise better blood flow more energy and then finally I just want to just have a glimpse into what the future might look like I told you we can we have a gene therapy that can reverse aging in a mouse's eye but what if it works in people what if it works in the whole body to reset the age of somebody I just chose Bill Murray because I like Bill Murray but you know he's he's aged right like everybody but imagine if if when we're young we get this injection of the gene therapy so now we're genetically modified but the genes are not turned on yet they're just like in our mice they're switched off they're not doing any harm and then you get to this age I don't know how old is Bill Murray now but he'd be sixty or something maybe even more anyway you get you get to a certain age and your doctor says I've just measured your biological age you're actually 85 you're not doing so well mr. Sinclair but I've got something for you fortunately you've got these three Yamanaka factors in your body I'll give you a course of doxycycline to turn on the genes so you get sent home with basically an antibiotic for Lyme disease not not a problem take it for three weeks and imagine you know you start to see better you don't have to see them hold the menu so far away you can think better you fit and you even look younger that's the kind of future that this technology says could be possible and then I just want to give you an example this is Exhibit A in my family we are a group of at least on my Hungarian side a group of Ashkenazi Jews that change their religion in World War two but we couldn't change our genetics we have terrible genes you probably know Ashkenazi's are not the healthiest people on the planet and I'm carrying a bunch of mutations so I'm not predicted to live a long time in fact most men in our family died in their 70s my grandmother had a stroke in her 30s super high cholesterol right I'm on I'm on huge amounts of lipitor just to keep my cholesterol down so we are not a healthy bunch so my grandmother she became she was she remember she was a young at heart vivacious woman rebel I watched her get old at age 70 she didn't want to go out of the house and she spent 20 years basically in a state of education in their lives it's pretty normal for us to spend 10 years not wanting to live anymore Hassan my father was born 1939 yeah people always say can about those that how can they be so close but I've told you I think she was pregnant 14 but in any case my dad he wasn't expecting to live beyond 70 in a healthy way just like his mom he retired at 67 he thought that he would probably end up in a wheelchair like his grown his mom and he wasn't very happy he was a quite a depressed guy he's like Winnie the Pooh in its no so he's like Eeyore in beneath food so he's not a very optimistic guy if he was here he'd probably say oh you know the temperatures not very good and and why are we wasting our time we're all gonna die anyway that kind of attitude in life and I was there like no no this is great we can do this so anyway he's a scientist he was a bike is a biochemist and he saw the research and he saw that I was still alive after taking a few of these things and he decided to take it as well so he's been now on the same regimen as me not just those three things but a few other things as well including a lot of exercise don't get me wrong there's other things going on but I'll tell you what he's um he's now 80 he started us a new career he's gone back to work he just ordered his dream car he just got it last week a Tesla Model 3 and he's optimistic I can't believe it I mean he's looking forward to another 10 20 years of life so I'm not saying that this is proof of anything but I am holding him up as a role model a beacon of hope for us and I'll show you some photos from the last 12 months of his life right this is not a typical 80 year old he's doing everything he always wanted we just got back he Ria's he led the way up the rain forest in Uganda he took his five grandkids up to see the gorillas and it almost brings a tear to my eye to think about how special that day was that he got to do that with his grandkids and my my kids got to do that with their grandfather that what this is all about this isn't about us living forever it's about spending quality time with your family instead of being in a nursing home so we're very proud of of him we hope he continues we hope it goes well and they're not I just want to finish by saying thank you for getting a copy of the book I hope you like it it was a lot of work I have a co-author we were we spent over a year brainstorming how to put this all together there's philosophy there's art there's history there's science all in there so he gets a lot of credit and I drew some cast of characters so they're in the back too I actually was trying to use photos of people and the publisher said David you've only got four weeks before this has to be done and none of those photos are allowable because they're copyright protected and I said well what if I what if I talk to people online and get your permission no because you have to track down who took the photo I mean I don't know if we took the photos right so I had to draw Lee so most people don't know but that's one of those inside secrets that I had to draw a lease and I only had a month to draw them so it was one every day for a month and there are a lot of really cool people this is the guy that trained me at MIT this is the woman who figured out that you could double a worm's lifespan by changing one gene that's probably a Nobel prize-worthy discovery my friend Ruffer de Cobo we spent Thanksgiving with he's the world's expert in calorie restriction neo browser lies the world's expert in metformin for aging he's down in New York and Sheena my discovered that nad is important and Anna man are important for the search one so these are all really cool people some people are really ancient so let's see we've got some historical figures up here this is this is misty Yamanaka Yamanaka factors eileen Crimmins studies human epidermal dimmi ology anyway this is so there are illustrations in the book did you have a chance to flick through there are actual illustrations drawn by Katie Delphia she's a brilliant artist examples of her drawings my childhood in Australia my grandmother me at MIT Benjamin Gompertz who showed the rate of population decay why we age how it evolved the CD analogy with the cell I didn't get into this but you can imagine the epigenome as a landscape of balls landing in valleys and aging is that the balls move into the wrong valleys and then metformin resveratrol nad rapamycin does anyone know where rapamycin comes from ah can you see those heads up there you know where they're from what's the name of Easter Island the other name Rapa Nui rapamycin so it comes from Easter Island there was bacteria that were found on Easter Island so I'm done [Applause] you

Channel: IVY

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Length: 106min 12sec (6372 seconds)

Published: Thu Jan 30 2020

Reddit Comments

[u/Isaacvithurston]

exercise, eat vegetables, get robot legs etc