Harvard Professor REVEALS How To SLOW & REVERSE AGING | Dr. David Sinclair

what gets really interesting and this is something most scientists don't even know about yet is level three the deep layer of aging there's actually a dna clock that tells our bodies how old we are we i could take your blood and read it and i could tell you roughly when you're going to die everyone welcome to health theory today's guest is david sinclair he's an acclaimed harvard professor who's doing some of the world's most ground-breaking work on human longevity he was named by time magazine as one of the most influential people on the planet and

his new book lifespan the revolutionary science of why we age and why we don't have to is set to permanently shift how we think about the inevitability of aging and possibly even death that is exactly where i want to start so this is my favorite topic i want to live forever i make no bones about it i know that right now though i'm on a collision course with death so you have a really interesting theory about what makes us age that if i'm not mistaken you call the information theory of aging so what exactly is

the information theory of aging and how do we take advantage of it so aging actually has been worked on for about 5 000 years or more and just in the last 20 years we've come up with a set of hallmarks of aging there are about eight of them and i think many of your viewers will know that there's telomere attrition the ends of chromosomes get shorter mitochondria the power packs will run out of energy as we get older there's a list a long laundry list and most of the people in in my field have said

okay we've we've figured out aging we've got this list we put in a nice pie chart and that's it but what i'm saying is that why does all that stuff happen it's not enough just to tick off what happens you have to understand is there an upstream cause of all of that and so in my book and in scientific papers we are now putting out for the scientific community to read as well what we think is going on is that our bodies are losing essential information as we get older that drives many if not all

of those hallmarks that we know exist so what in what way is the epigenome involved in this how are we losing the information give people a quick little diatribe about the difference between genetics which i think they get and then the epigenome and epigenetics and and how that plays out yeah yeah for sure it's not that complicated there's really just two main types of information in our body that we get from our parents the first is genetic we all know about dna and the four letters atcg it's a long molecule in cell and it's a

string of letters that's digital that's like the music that's on on a dvd those things we used to use uh to store movies but there's another level of information that's above that in the cells which is the reader of the information that's called the epigenome and that really is different because it's analog information in the same way that records and cassette tapes they sucked they were terrible at storing information but the problem is we have an analog version of information the epigenome which controls which genes in the string of dna are turned on and off

and that's why are you considering that analog i don't think i understand how it actually works like i can imagine dna sequences as just sort of repeating the atcg code but what is analog about the epigenome this reading about it in your book is the first time that i began to imagine it in a different way well it's very clear that that if you just have four letters that's digital so we understand that but the epigenome is the structure of how the dna is organized so dna isn't just flailing around like a string it's actually

packaged up around proteins we call histones and it's like if you spool your hose in the garden you loop it around and then you can put those loops into bigger structures then you get a chromosome which you can see any high school student can see under a microscope that's that chromatin structure as we call it is the epigenome and so when when the hose is looped tightly and spooled up that's stopping genes from being red so genes are off when they're compacted but also if the cell needs to read certain genes and a nerve cell

needs to read the nerve cell genes and the liver cell needs to read specifically the liver cell genes and so they open those ones up and now the cell can get access and read those that's an analog system because it it's varying all the time it changes when you wake up what you eat so it is literally the amount that the um the dna is unspooled and the place in which it is unspooled so that it can be read right and that's what determines the cell's function and identity which we you know when we're born

where 26 billion cells each one of those cells knows what it is and what it has to be 80 years later it and its descendants and over time what i'm saying is aging is caused because cells lose their packaging and then eventually cells lose their identity disease ensure ensues cells check out they become zombie-like and they're now in essence right senescence and then our organs fail and we die but until recently we had no idea why that was happening and so why is it happening well so the the packaging is the really important part because

much like the software runs the code the epigenome controls which genes are on and off and if you stress the system and by that i mean biological stress and the biggest stress you can cause to a cell is to break its chromosome because it's going to die if that if it doesn't fix it or worse for the body you get a tumor so the cell has to hunker down stop dividing arrest just about everything it's doing and then try to repair that broken dna but in doing so it has to do two things first of

all it has to take proteins from somewhere else that are doing a good job keeping the cell from functioning or making sure the cell's functioning correctly and those proteins are used by the cell to repair the dna that's broken but also what's happening at the break is that that's all opening up as well because you remember if you break a dna and it's spooled up you can't fix it you can't glue it back together unless you unpack it stick it back together and then you've got to repack it so this movement of proteins and the

unpacking repacking of the dna i believe leads to cells losing that original youthful what we call a gene expression pattern of how the genes are turned on and off and nerve cells as they get older lose their ability to stay nerve cells and liver cells lose their identity as liver cells all right so do proteins the way that you're talking about them sound like little creatures i think of them because of my background like powder like just sort of inert molecules which clearly judging by the way that you're talking about them they're not i've seen

them animated before as having like articulatable shapes and they actually move is that accurate that's essentially it it's it's super exciting when you realize that proteins aren't just blobs or powders in the cell they're actually little little machines like pac-man that go around and they can change the function of other things they can package the dna and what they they do is they create chemical reactions that normally would take a billion years to happen this is what an enzyme does it accelerates reactions and so we've got about 20 000 different types of enzymes in the

body and they do different things but what we've discovered over the last 20 years is there are certain types of enzymes that help package the dna and help with the dna repair these are the ones that doing the ping pong game and without those we're screwed we basically will will age more rapidly conversely what's really exciting is we've discovered that you can make them more active to make sure the dna is packaged correctly and the repair is very efficient and there are ways you can do that exercise dieting being hungry they allow these enzymes that

control our body and make us healthier they make those enzymes much more active so instead of a pacman doing this you exercise your diet take them take a molecule that we work on and it'll go around and fix everything much more efficiently and keep you younger for longer we think why do you use the pacman analogy which makes me think of it's eating something is that what's happening is it eating cells that have a level of senescence or is it uh more bob the builder and it's going around tearing some things apart putting some things

back together yeah it's more like bob the builder but i think a good example for at least the enzymes that we work on called serotonins that protect the body they're like a little tiny pair of scissors they they chip up clip off chemicals called acetyls and in doing so when they clip off the acetyls off those packaging proteins the dna gets more compact and that's called gene silencing and over time as we get older and through this dna damage process the sirtuins get inactive they're distracted by dna repair and the packaging of that dna that

that hose spooling starts to loosen and now genes that have no business being on in the brain come on and partly i believe that's why we we have these diseases of the brain [ __ ] that's so interesting um okay so one i want to know from a lifestyle perspective what are we doing that's speeding that up and then two what can we do from a lifestyle perspective to begin slowing that down and reversing it well so i've been studying these enzymes the sirtuins we have seven in our bodies i've been studying them for about

25 years and what we've learned is that they respond to the cellular environment there's a chemical that they require for gas think of them as the fuel called nad and there's another molecule that is like the accelerator on the enzymes uh that makes them going even faster and that's one of them is called resveratrol which we discovered years ago from red wine and together they actually do really great things on these enzymes and make them keep the body younger at least for 25 years we've been studying mostly animals and even little fungi yi cells and

what we've learned from those studies is that these are largely involved in responding to when organisms are under threat of survival so how do you make the body feel like it's under threat adversity uh so one is run a lot or at least become out of breath you know a few times a week your body will say oh man we had we had to outpace one of those saber-toothed cats again gotta go to build up the body um the other is to be hungry either a couple of times a week or every day you know

skip a meal or two and then your body will turn on these sirtuins make more of that fuel nad for the enzymes and we think that's what's in part responsible for the health benefits of those uh lifestyle choices all right one thing though that you talk about that i found really interesting is this notion of what may be good for you when you're young may come back to bite you in the ass when you're older yeah so it's like um the whole notion of hormesis that a little bit of bad is actually extraordinarily good which

is exactly what you're describing now get out of breath do all the stuff and so when the information started pouring out that the only thing across every known um living organism that extends lifespan is to eat less which you talk about in your own book it feels like you're saying to do it for that reason just don't put as much stress on the system but now i hear you saying no no what you actually want to do is stress the system won't that stress of i just ran from a lion a [ __ ] starving

won't that begin to stack up and become problematic well actually if you step on a snail it's going to die so there's certain amounts of stress that that you don't want to do but what you want to do is get the body to fear adversity in the future but not enough to cause lasting damage or the unspooling of the dna that'll lead to disease and eventually death so you you don't want to overdo it you want to be a little bit puffed you want to be a little bit hungry but of course starvation malnutrition is

not going to make you live longer so it's a fine line and what we've learned from many animal studies and increasing numbers of clinical trials in humans is that you want to pulse it let the body recover not constant we used to make animals go hungry all their lives and it worked but it actually works better if you let them recover and i think that's that's the secret then let's really dive into that so i'm guessing you're talking about where um animals were denied something like 20 to 30 of their caloric intake for very long

periods of time is extending their life by what like 30 or something um so super interesting but you're saying that if their caloric intake over a long period of time is roughly the same of an animal that's just allowed to eat until it's satiated that if it's done in a pulse pattern of hunger and and almost over feed they actually have the same benefits as the animal that has a chronic deficit of calories all right well let's be clear nobody knows what the perfect diet is even when it comes to fasting it's all largely based

on rodent studies so what i can tell you about the rodent studies which i'm very familiar with is that if you take a rodent and reduce its calories by 25 for its whole life it will live longer 30 but it'll be really miserable and aggressive uh and that's true for us as well i've tried calorie restriction for about a week and i gave up i was pretty angry but what we discovered my colleagues um discovered is that if you it's not just what you eat it's when you eat that's important and what's been found is

that if as long as you have that period of hunger um in a mouse so you can feed them every other day then they can gorge themselves as much as they want and they do they eat about 90 of what a mouse having free access to food would eat but they they have the same longevity benefit as a mouse that's always been hungry and if that's true what that means is for us is that we can enjoy life as long as we have that period of hunger once a day or maybe twice a week and

i believe the only reason we age you know we could live for a thousand years otherwise the only reason we age is that our repair systems become complacent you mentioned that what what is beneficial for you when you're young come back to bite you when you're old what we think is that these repair systems are very good when we're young so the idea is it's called antagonistic pleiotropy and i think it's right and that is that we evolved to stay healthy and alive and fit till we're 40 and then the forces of natural selection decline

after that because we've essentially bred we've often had children but we don't need to stick around beyond that and building a body that will last a thousand years is pointless at that you know so most species only live as long as they need to to reproduce and then a little bit more if you're a mouse that could die within two years they only build a body that lasts two years if you're a whale that has no predators you can live for a couple of hundred years that makes more sense why why does the whale live

for a couple hundred years like i would say it's pretty safe to say certainly at some point in our past we became a pretty clear apex predator it's not that things couldn't take us out but i mean by and large obviously look at how far we've come they didn't so why would we only live to 40 is it that whales continue to breed and be useful in that sense so that's really super interesting very few people talk about this the reason is that we were not at the apex of the food chain until recently but

in a world where we typically would die from starvation or from war a lot of men didn't make it to 40 because of that we were at the middle of the food chain only now we we actually barely have a chance of dying before 70 or 80 unless we're unlucky give us another 5 million years of evolution we could evolve 200 year life spans that's what should happen if evolution continues a whale has been at the apex for about 30 million years and they've been allowed to evolve those long lifespans we are just like them

we share most of their genes they're warm-blooded they produce milk they're conscious they're basically us in the sea so anyone who says we've reached our maximum limit doesn't know what they're talking about talk to me about this notion of resetting the biological clock how do we do that what's the mechanism and so obviously going hungry occasionally exercise is going to help but i know that you have a regiment that i'll lovingly call a regiment of drugs or precursors to things that we can take what can we do to reset that biological clock well there are

different levels to resetting aging there are three levels that we know of the first is pretty easy to reset or to to manipulate these are the proteins that turn genes on and off very quickly we call them transcription factors and they they basically read a gene and make a protein that's what they do that's level one that's easy go a little bit hungry that'll change level two is a little bit harder the level two is not just changing which genes are quickly turned on and off but actually silencing genes for for a long time and

this is where my enzymes that we work on the sirtuins come into play let's go back to the pacman they clip off acetyls off these packing proteins you spool up the hose and it becomes becomes locked in that gene gets silenced for a long time so to do that you can exercise you can diet but you also i think you need a little bit of help as well what gets really interesting and this is something most scientists don't even know about yet is level three the deep layer of aging there's actually a dna clock that

tells our bodies how old we are we i could take your blood and read it and i could tell you roughly when you're gonna die what yeah we can do that what are you looking for we're looking for chemical groups that get added and subtracted to our dna the long string in the cell you get chemical modifications in predictable ways as you get older starting from conception so even in the womb even as a kid even as a teenager you're aging based on this clock that goes up linearly and where you fit on that line

it's very accurate that tells you your biological age but how do you know when the person is going to die is that just based on straight lines is it actuarial tables though the human average human lifespan is 86 and is that what you mean or is there could you see something specific in my line that would say you're headed for 68 sorry no it's not not specific but what it's based on is machine learning based on thousands of people's um code of methylation on the genome and comparing that to their health and their date of

death oh [ __ ] that's so interesting so if you were to take my blood right now what would you look for exactly we would read the methylation the kemp these are chemicals hydrogen and oxygen bound to the dna chemically physically bound and those accumulate as you get older in very predictable ways in fact they're so predictable that we can use the same clock to measure the dog's age and a human's age whoa all based on methylation right okay what causes methylation well there are two classes of enzymes the ones that add the methyl chemicals

and those that subtract it okay how do i take a boatload of ones that subtract it ah that's what we're working on now here's the key level two aging reset which we can do by some of the things that i'm doing in my life yeah probably you are too those aren't permanent changes you can't just do that and expect that take take one treatment and you go on living for another 10 years okay because level 2 isn't as permanent it's somewhat permanent than level one but level three is truly permanent it you could reset yourself

ten years and then go back and then wait another ten years and potentially reset the clock again if you know how to do that and we're just starting to figure out how to do that okay so level one diet exercise cool got it level two uh metformin you taking metformin right okay so i've talked about this on the show before but explain what is metformin why is it prescribed to diabetics and now why is a seemingly rash of non-diabetic people taking it yeah so there are three main pathways that regulate aging in animals and probably

in ourselves there are the sirtuins that i've talked about a lot today there's one called mtor which responds to how much amino acids or how many amino acids are in your body it will hunker down and protect the body the fewer amino acids it has access to okay okay then the third is called ampk and this is the energy sensor when your body has low levels of energy it will allow the body to hunker down and protect itself from diseases but why ampk is worth mentioning is this is one of the targets as we call

it of the drug metformin metformin will activate this ampk pathway and make the body think that it's hungry when often it's not and also keep your blood sugar levels more steady why would i uh hungry at a cellular level or i actually experience hunger at a certain level okay but it also has an interesting side effect is from for a lot of people myself included it's a bit harsh on the stomach so it also reduces my appetite but what's great about metformin is that it's been in millions of people for a few decades so we

know the side effects they're relatively i'm sorry really fast so metformin is creating at a cellular level the sense that i'm hungry and you're saying that from a hormesis perspective of a little bit of bad it's like stressing the system and that's why we think it works it is it's exactly doing that and so that it actually helps the body respond in a way to boost the energy supply so one thing it does that's that's undeniable is it boosts the level the numbers of mitochondria it actually creates additional mitochondria so your cells are getting more

efficient or more able to generate energy right over the long run but in the short run what it does is it actually poisons part of the mitochondria so it's it's a little bit of poison that leads to benefits down the line what part is poisoned uh it's called complex one so that there are protons that are in one part of the area of the mitochondria in a in a membrane region and you the cell builds up protons it becomes really acidic in that region but they the cell wants to release them so what they do

is they put little pores in between the membranes so they can leak from the high concentrated zone to the low concentration in the middle and as they pass through that pore it spins the pore around and that spinning physical spinning of that protein will generate chemical energy called atp that's how atp is created and without atp we're dead in about 10 seconds yeah okay that's crazy interesting uh and you're saying sorry to go back to the poison the poison is elevating those levels which is causing more to go it's actually decreasing atp in the short

run so the cell says man i haven't got enough chemical energy in atp so that's what forces it to create more mitochondria right so that's the poisoning part it is so the increased number of mitochondria is in response to the slight poisoning exactly but there are two other important points the cells in our body also think that they need to become more sensitive to insulin yeah which keeps our glucose and sugar levels more steady okay yeah that's key because that's what helps the diabetes type 2 diabetics recover and you know prevents the disease from getting

worse yes the second is that it's just been discovered in humans that if you take metformin a lot of it and exercise it can blunt the effects of exercise on building mitochondria what we think is going on is that you don't want to always have metformin in your system or your body won't have a chance to recover from that slight poison i'm not going to prescribe anything i'm not a doctor but we think it's best better to take metformin on days that you're not exercising and recovering and pulse it again so you've got metformin exercise

metformin exercise right i know you're not prescribing anything but uh how many days are you taking it how many days are you not how often are you exercising how often are you not um i actually spent a lot of my 30s and 40s not exercising at all it's crazy right someone like me but i've become better at it now that i'm you know i was approaching 50 now i'm 50. uh so i spend about four hours in the gym on the weekend with my son benjamin dude like two hours a day no four hours straight

but it's not all exercise okay so it's an hour with my trainer sean who does mostly a combination of weights and stretching um some free weights some machines then it's another hour on my own with my son we do some treadmill some more stretching and essentially just muck around doing stuff that's fun for him and then we also then we do some some yoga downstairs in the gym a little bit of relaxation but the best fun part that i really love is at the end we do a sauna hot tub cold bath sauna hot tub

cold bath for about an hour and i feel fantastic talk to me about that so in your book you go into cold exposure you said you moved to boston it sucked coming from australia and you bundled up and now you wish you hadn't um why cold exposure is cold and hot both necessary what's the difference well there are a few reasons one is the high level view is that anything that stresses your body puts it into a state of shock is good in the long run but a little bit of perceived adversity being a little

bit too hot a little bit too cold and especially the gradient between those two which is why we jump from one to the other the next point is that i've looked at the literature and at first when uh i was prompted by my publisher to look into this scientifically they said you know what about this cryotherapy what do you think and a couple of years ago i had no idea that this was real it sounded like [ __ ] to me but i looked into it and there were there are two important things one is

cryotherapy or cold exposure we'll build up what's called brown fat we didn't know brown fat existed in humans until about five years ago typically it's across your back and in other reasons you can see with a pet scan but otherwise it's pretty invisible just looks like fat but brown fat is particularly healthy because it it has a lot of mitochondria and we think it also secretes little proteins that tell the rest of the body to be healthy in what way to be healthy we're not sure yet we're not sure it's interesting oh man i want

the answer to that question but it certainly revs up your metabolism and will burn energy if you're looking to stay lean having a bit of brown fat is all good so my my friend ray cronus and i have written on this and andrew bremer and at the nih we call it the metabolic winter hypothesis and essentially it's saying that in our lifestyles these days we're always warm i'm wearing this jacket we sleep with the covers on we turn up the heat we never get exposed to coal unless we force ourselves to and we think that

that's possibly largely responsible if not you know maybe partly perhaps largely responsible for the diabetic problem we have what okay so if if you're cold at night you're going to burn a lot more energy staying warm yes turn on your brown fat now that's going to keep people lean if we bundle up and and we eat the kind of diets that that we see in the supermarket that's going to be doubly bad for our bodies yeah we're warm we're not losing energy and we're eating a lot more yeah this is this stuff is so interesting

okay so what's your advisor i whatever you're about to tell me no i'm going to do it so like how frequently do i want to be doing it is it every day what's that look like well what i do is because i'm busy and i don't have a sauna or a cold tub at home i subject myself to this stuff um for about an hour on sundays and what i do is i spend about 15 minutes at 150 degrees fahrenheit well that's reasonably intense but you get used to it then we go into the steam

room um you know we're sitting there chatting it's great uh temperatures lower in the steam room because the humidity is saturated the roof's dripping on you hot water uh but that that i i don't know if the steam helps but i certainly love the feeling of being in there and my skin starts to be healthier because of course it's cleaning itself out and then the final thing i do is hot tub pretty hot hot water and then and then i go and dunk below the water a couple of times in water that's less than four

degrees celsius so that that's so cold that it takes your breath away yeah yeah but it's great interesting was there anything else on level three that we should know about yes so work that we've done recently uh just in the last year is finding ways to tweak the cells and the tissues of of mice at least to reset the clock we've been working for 10 years as i said accelerating the clock we can drive that hand of the clock forwards now we we cut the dna of the animal let it heal and in doing so

we distract those proteins from where they come from so we're disturbing this survival circuit so much that we disrupt the spooling of the dna and what we got was an old mouse by every account based on histology which is looking at the tissues based on their physiology they got gray they got arthritis they got heart disease even and when we look at the molecular clock that uh methylation clock they were 50 percent older communications they had more like clumps everywhere uh those methyl groups were added to the dna right right okay so we had given

them heart disease and alzheimer's or dementia we'd given them all these diseases but by measuring the clock what we'd actually done is give them aging but that that was the first step that took 10 years the last year we've been asking how do you get the hands to go backwards that's a lot harder but we were fortunate that the 2012 nobel prize was one for the ability to reverse that clock in cells it's called uh it was the prize awarded to shinya yamanaka a japanese fellow very smart guy and he found at least four genes

that when you put into say skin cells of an adult if you gave me your skin cells i could go back to laven basically clone you i could take your cells make a stem cell pool and i could grow you into a new little liver or a new little kidney that's all easy not easy but it's doable it's doable um what that tells us is that those four yamanaka genes can reset age if i can take someone who's in like you who's in their early 40s and make a new you as we've done now for

many species dogs cats sheep monkeys those animals we can reset the clock hundred percent and those animals actually live a normal lifespan that tells us that the instructions to be young are still in the cell somewhere as though there's a backup hard drive that tells the epigenome those spools had to go back to be young again and get those methyl groups back to being young again not up here but back there but don't strip them off too far to be a stem cell or i'll basically turn you into the world's giant tumor yeah okay so

one why do i become a tumor because a tumor is a cell that doesn't know to stop right so what is it that you're breaking in that process that that makes it so um dysfunctional yeah so in terms of the clock let's just start with that shiny yamanaka wound the clock so far back it went back to zero back to midnight that we do not want to do because the cells lose their identity and that's the last thing we want to do we don't want to go back to us because it's dangerous to have a

pluripotent stem cell in the wrong place in the body of course it'll grow it won't stop growing but why doesn't why why does it become a tumor why doesn't it become a liver or a lung like i would get the problem of having a liver develop in my brain but i'm just saying like why does it become a tumor cell instead of an actual functioning liver uh well so when you go back far enough and it loses its identity it will just multiply into a mass without cellular identity so there's something else going on that

stops it from figuring itself out right so in the lab if we take a pluripotent stem cell and we want to make a liver cell or a neuron a nerve cell we give it a bunch of chemical signals in what we call the niche and when one of these cells lands in a niche around those old cells they'll use that stem cell to rebuild tissue but imagine if we could reset the clock not all the way back to a stem cell but just partial reset the clock so so that you could go back to being

20 again right that's what we're able to do in some tissues in the mouse right now you do it on mass when it's cell by cell dna strand by dna strand like how the hell do you get this to take effect through a whole joint let alone the whole body yeah right now the way we do it is we inject a virus called an aav and this virus will target certain tissues and deliver the genes to most of the cells in that tissue for example we are treating aging of the eye in mice so we

can take an old mouse we deliver a virus the av into the eye tiny little prick it's the same virus that that's used to correct genetic deficiencies in the eye right now fda approved drugs so this isn't science fiction this is out there in in the world right now we give it give it to the old mice we give them an answer about it antibiotic called doxycycline okay same thing you might take if you got lyme disease and that turns on these reprogramming factors we don't use all four of the factors oskm they're called because

one of them causes cancer the m we leave off the m we put osnk into the eye turn it on leave it for a few weeks measure what happens to the eye and those mice can see again like they were young so we've tested three different types of damaged damage to the eye the first one we did was a hail mary so that a lab near ours across the road works on rejuvenating the spine and the optic nerve which is crazy yeah because we know as soon as you're you know a couple of months old

you're not going to regrow a spine it's one of the first parts of the body that ages in fact but jellyfish can regrow axolotls can regrow an arm we lose that ability when we're very very young so we the question was if we turn the clock back a lot without osk genes will those nerve cells be young enough to regrow back to the brain if we damage them and that was the experiment they pinched the back of the optic nerve so that the nerves were defective and they started to die back towards the brain of

course the mice lost their vision we then turned on our reprogramming factors we now see that the nerves get young again wind the clock back and they regrow back to the brain we could give ourselves the healing ability that we only had when we were embryos and you start to think about what could this lead to if we can do this safely of course safe is the important word across the body imagine one day you could have every cell in your body able to be rejuvenated like that you cut yourself you break a bone you

lose your your mind you have a dementia you take a course of doxycycline for a few weeks and then stop switch it off again and you you heal if you turn it on at high levels there's a lab in spain that has shown that you can get small tumors in some animals in the kidney so we've been very careful to not just blast the cell with these factors permanently we've titrated or we say brought the levels down to very low levels and switch it off when we don't need it but we have given mice uh

this virus throughout their body we inject it into a vein and we turn it on we've left it on now expecting the mice to die a year later they're perfectly fine wow so it appears to be safe but of course there's a lot more work to do i'm a scientist and i'm developing drugs i have to be very aware of the dangers sure please nobody go out and try this at home at all until we know more but the eye is a good testing zone because it's it's protected and if there's a problem it's you

know it's shielded from the rest of the body it won't go too far but everything we know now is that it seems to be very safe at least in the eye wow this is crazy so that is is there an element of getting better improvement human performance or anything that um you can tease us with well we we've actually uh published results that in mice if you give them an nad booster molecule that will turn on these pac-man enzymes called the sirtuins those mice when they're old can now run 50 further in fact some of

our old mice ran so far that the treadmill stopped because mice are not supposed to run more than three kilometers we haven't talked about nad yet tell me what nad is what are the precursors how do i supplement for it uh so there are a few on the market i i don't endorse or sell anything just by the way even if you see me on line that's not me so that said there are there's one called nr which is stan which stands for nicotinamide riboside which is a very early precursor to making nad in the

body there's an intermediate from that called nmn not to be confused with m ms please don't do that that's not healthy and then the cell turns nmn into nad and you can take all three actually and or each one of those three and raise nad levels in animals and now we're doing myself and many others are doing human studies and we've seen that nr and in my case nmn does raise the energy levels of older people and and young people alike up to levels that we think you could rarely achieve even with uh being a

marathon runner that's crazy so just to bring this home for people talk to me about your dad and his uh n of one experimentation with nmn yeah so my father has been on the same regiment as me resveratrol for over a decade the red wine molecule he's been on metformin longer than me because he had he was a borderline diabetic type 2 diabetic and he's also on a man now and he seems to be doing great he's now 80. when he was in his 70s he was he was slowing down his he was starting to

say the same things twice you know typical 70 year old he's doing great now he's 80 he's got a new lease on life he started a new career down in sydney he's hiking at the world right now he's traveling around america driving his elderly friend uh around his friend unfortunately ended up going to the hospital the last few days so my father is taking care of his friends who he's seeing on the decline and he's if anything improving every year i'd love to hear more about resveratrol which is something that i've completely written off until

i started researching you um it seemed for a red hot minute like it was real and then it seemed to completely die and i know that you got sort of caught in the middle of some of this stuff so where has all the forget like what pop culture thinks of it like what's the reality of it yeah so resveratrol was a proof of concept molecule back in 2003 the first of its kind that could mimic caloric restriction make mice healthy on a high fat western diet and it was it was a great proof of something

that we were trying to figure out and it led to drugs that went into humans that looked really promising i got embroiled in a scientific and a a corporate war song in the case of pfizer they put out a scientific paper that said essentially everything that david has said is wrong okay and then that was a great headline harvard scientists started companies is wrong okay and you know and then i spent about a week in bed saying [ __ ] the world you know why am i doing this why am i working so hard for

society if they don't care but i worked my way out of bed i thought let's dig deep and see if they're right or if we're right and so for another three years we really worked hard in my lab at harvard to test whether we were right so the question was with this pac-man that spools the dna does resveratrol work on it or is it working on something else and that to scientists is really important because if it's not working on this all the drugs that we're trying to work on this are probably working um the

wrong way that we thought to cut a long story short what we found and published in the journal science which is one of the top you can do and i say that because it's validated science is that we show that resveratrol does bind to the pacman and it is responsible for this and we now have new information that we haven't published but i'll tell your audience about it we've made a mouse that is resistant to activation of the pacman we can tweak the enzyme just in one amino acid in that protein out of about a

thousand that blocks this movement activation it's normally chewing like this but if we add resveratrol to a normal mouse it'll do that to our mutant mouse it's this and which is better the rapid munching rapid munching's better okay because the rapid was we think was responsible for the health benefits and the longevity so what you're showing is by slowing it down you cause real problems and thusly if you have resveratrol on there and get it munching really fast that you've done something positive right and our mutant mouse should be resistant to the benefits of resveratrol

if we're right but if pfizer is right then resveratrol should still provide benefits even though this enzyme because it's working on some other some other way got it so the mouse that could not be sped up the mutant mouse does not live longer when given resveratrol on its high fat diet interesting so that will be the the punctuation mark the fu we will ride but but interestingly the world has moved on right well i'm left to clean up the pieces right yeah so and when you say the world has moved on you're talking about people

like me who just assumed that it was garbage and that it's not real and right okay so um you've said that the only supplement you take is vitamin d um so how are you getting resveratrol in the system is it a drug do you have to have it prescribed uh well i'm taking resveratrol i have um and would we call that a supplement sure and it's commercially available uh it is if it's a legitimate seller and it's 98 plus percent pure it seems to be similar to what i take and ballpark how much do you

take um i take a teaspoon into my yogurt that's probably close to a gram every day every day yeah okay uh resveratrol roughly a gram are you taking nmm or is nmn or is that just your dad uh both of us okay and then um metformin right those three anything else those are the main things that i think are helpful and i've been monitoring my blood by chemistry so i and you said you took an mri of your heart right which i love what are things that we should be testing assume for a second i'm

willing to go all the way do any crazy test to know if what i'm doing is working um what would you recommend well i avoid x-rays and ct scans unless i have to sure right if your doctor says go for it please don't refuse that but otherwise don't do it for fun don't do it because you're curious uh because those ct scans will break your dna and when we break the mouse's dna it's a its age goes up by 50 percent so whoa right so avoid dna breaks as much as possible what i do is

i take a blood test from a company called inside tracker which in full disclosure i invested in years ago and they look at about 30 parameters in your blood and give you feedback it's doctor supervised so it's it's legit and it's based on a lot of science and that at least gives you some feedback about your body about what's actually happening if you change your lifestyle or you take a supplement or even a new drug for that matter so you've got to have you've got to be monitoring because you don't you don't want to fly

blind you don't know if for you you're doing harm or doing good so do do a blood test at least go to your doctor and have a blood test for for a good goodness sake you could have your genome sequenced or do something that looks at the the variance in your genome for relatively little cost i think it's 99 now i gave a test of that kind to my whole family as christmas present and what we've learned is that some of our members lab members are not lab members family members have variants that predict longevity

some don't some have mutations in their genome that are a little bit scary um down the line you could get your dna methylation age determined the true what's called the horvath clock some people measure their telomere lengths um did you have a biopsy to do that or can you do it from blood blood blood test is fine yeah so interesting all right where can people learn more about you uh well so the main site is lifespanbook.com that's where you can sign up for the newsletter and uh buy a copy of the book if you're interested

i highly encourage it well thanks i'm also um now on social media so i have a twitter account i try to talk about the science about new findings about things that i've just learned and stuff like this that they might want to tune into so my twitter account is david a sinclair and i have instagram where i send out some you know little fun to do is not to do this kind of thing and that's david sinclair phd okay what's the impact that you want to have on the world well that's easy since i was

four years old i've wanted to figure out why we die so fast and you know in my view i think it's cruel to have a sentient being that knows it's going to die in such a short time frame 80 years is nothing it goes by in a blink of an eye even a thousand years will go by in a blink it's only 20 times what i've lived so i want to be able to leave a mark on the planet i'm hoping to have moved the needle somewhat on the course of human history i think we've

we've come further than i thought we would in my whole lifetime and this i've still got a few years left to try and make what i'm talking about come true i certainly hope so if you were going to have people make one change that would have the biggest impact on their health what change would you have them make well so having read tens of thousands of papers and done this for now 30 years and talked to people and i know what's on the cutting edge the simplest thing you can do that would have the biggest

bang for the buck is be a little bit hungry don't eat but that's not to say be nourished don't don't starve yourself right there are a lot of teenage teenage girls particularly who don't eat enough so i'm not saying that at all you've got to have a minimum nutrition but for those of us myself included who likes to eat those of us who don't mind a bit of dessert try to skip a meal i skip breakfast besides that bit of yogurt often i'm too busy to eat eat a lunch at dinner i eat a normal

meal i don't gorge myself because that'll trigger all these defensive pathways that'll rebuild the body or at least keep it pristine until we have such things as the level three reversal which we're now working on that's amazing david thank you so much for being here that's incredible and guys read the book dive in if you're like me and you want to live forever i'm telling you this guy is at the tip of a very exciting sphere so check them out if you haven't already be sure to subscribe and until next time my friends be legendary

take care my man that was [ __ ] awesome thank you guys so much for watching and being a part of this community if you haven't already be sure to subscribe you're going to get weekly videos on building a growth mindset cultivating grit and unlocking your full potential you