This Harvard Professor Explains the Secret to Aging in Reverse | David Sinclair on Health Theory

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 hey everyone hope you enjoyed this episode brought to you by our sponsors at Peak tea 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 groundbreaking 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 this 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 they're 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 we're running out of energy as we get older there's a list a long laundry list and most of the people in my field have said oK we've we've figured out aging we've got this list we put in a nice part 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 exists 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 to store movies but there's another level of information that's above that in 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 in men or cassette tapes they sucked they were terrible at storing information but the problem is we have an analogue 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 could 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 read 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 so they open those ones up and now the cell can I 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 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 we're 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 and so ensues cells check out they become zombie-like and then our own essence our 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 gonna 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 is 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 good job keeping the cell from functioning or making sure the cell's functioning correctly 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 pulled 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 and 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 the 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 articulate able shapes and they actually move is that accurate well that's essentially it it's it's super exciting when you realize that proteins aren't just blobs or powders in the cell there are 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 do is they create chemical reactions that normally would take a billion years to happen this is what an enzyme does that 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 twenty years it's 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 you 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 pac-man 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 more Bob the Builder and it's going around tearing some things apart putting some things back together yeah it's it's more like Bob the Builder but it I think a good example for at least the enzymes that we work on called sirtuins that protect the body there they're like a little tiny pair of scissors they chip up clip off chemicals called acetals and in doing so when they clip off the acetals of 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 an 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 dock that's so interesting okay so one I want to know from a lifestyle perspective what are we doing that's speeding that up and then to what can we do from a lifestyle perspective to begin slowing that down or 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 twenty-five years and what we've learnt is that they respond to the cellular environment there's a chemical that they require for gas think of them as a fuel called nad and there's another molecule that is like the accelerator on the enzymes 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 yeast 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 so one is run a lot or at least become out of breath you know a few times a week your body will say old man we had where to outpace one of those saber-toothed cats again got to go to build up a body I'm 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 in ad for the enzymes and we think that's what's in part responsible for the health benefits of those lifestyle choices alright 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 the whole notion of hormesis that a little bit of bad is actually extraordinaire which is exactly what you're describing now get out of breath do other stuff and so when the information started pouring out that the only thing across every known 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 [ __ ] I'm starving won't that begin to stack up and become problematic well actually if you step on a snail it's gonna 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 and 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 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 animals were denied something like 20 to 30 percent of their caloric intake for very long periods of time is extending their life by what like 30% so super interesting but you're saying that if their caloric intake over a long period of time is roughly the same as an animal that's just allowed to eat until it's satiated that if it's done in a pulse pattern of hunger and an almost over feed they actually have the same benefits as the animal that has a chronic and 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 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 discover my colleagues 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 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 to wear for tea 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 at how far we've come they didn't so why would we only live to forty is 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 men didn't make it to 40 because of that we were at the middle of the food chain only now we we actually we barely have a chance of dying before 70 or 80 unless were unlucky you know give us another 5 million years of evolution we could evolve 200 year lifespans 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 regimen that I'll lovingly call a regimen of drugs or precursors to things that we can take what can we do to reset that biological clock mm-hmm 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 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 a long time and this is where my enzymes that we work on this or to incumbent they clip off acetals off these packing proteins you spool up the hose and it becomes becomes locked in that's 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 can 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 mark that the long string and so 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 will you fit on that line it's very accurate that tells you your biological age but how do you know when the person's gonna die is that just based on straight lines is the actuarial tables oh the human average human lifespan is 86 and is that we 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 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 Kempe 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 he's the key level to Aging reset which we can do by some of the things that I'm doing in my life yeah probably you are - 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 ten years okay because level two isn't as permanent it's somewhat permanent then 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 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 am i k 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 hungry at a cellular level or i actually experience hunger at a stereo 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 the relative lengths are 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 on what it does is it actually poisons part of mitochondria so it's it's a little bit of ploy and that leads to benefits down the line what part is poisoned it's called complex one so that there are protons that are in one part of the area of the mitochondria 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 its bins the pore around and that's spinning physical spinning of that protein will generate chemical energy called ATP that's how ATP is created without ATP we'd get in about ten seconds yeah okay that's crazy interesting and you're saying sorry to go back to the poison the poison is elevating those levels which is causing more 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 poison 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 two diabetics recover and you know prevents the disease from getting worse yes and 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 got metformin exercise metformin exits all right I know you're not prescribing anything but how many days are you taking it how many days you not how often are you exercising how often are you not I actually spent a lot of my 30s and 40s not exercising at all it's crazy right someone like me hmm but I'd become better at it now that I'm you know I was approaching 50 now I'm 50 so I spend about 4 hours in the gym on the weekend with my son Benjamin dude like 2 hours a day no four hours straight but it's not all exercise okay I saw it's an hour with my trainer Sean who does mostly a combination of weights and stretching 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 it'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 often talk to me about that so in your book you go into cold exposure you said you moved the boss and it sucked coming from Australia and you bundled up and now you wish you hadn't why cold exposure is cold and hot and 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 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 will build up what's called brown fat mmm-hmm we didn't know brown fat existed in humans until about 5 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 interesting I mean 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 or is all good so 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 you know 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 cold 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's okay so if you're cold at night you're gonna burn a lot more energy staying warm yes turn on your brown fat now that's gonna keep people lean if we bundle up and and we eat the duck kind of diets that that we see in the supermarket that's gonna 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 advice 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 everyday 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 for about an hour on Sunday 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 you know we're sitting there chatting it's great temperatures lower in the steam room because humidity is saturated mmm the roofs dripping on you hot water but 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 mmm 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 just in the last year is finding ways to tweak the cells and the tissues of mice at least to reset the clock we've been working for ten 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 grey they got arthritis they got heart disease even and when we look at the molecular clock that methylation clock there were 50% older communities if they had more like clumps everywhere 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 had actually done is give them aging but that that was the first step that took ten 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 won for the ability to reverse that clock in cells it's called was the prize awarded to Shinya Yamanaka at 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 you your skin cells I could go back to lab and basically clone you I could take yourselves 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 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 she 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 how 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 giant tumor yeah okay so one why do I become a tumor because the tumor is a cell that doesn't know to stop so what is it that you're breaking in that process that that makes it so dysfunctional yeah so in terms of the clock let's just start with that Shinigami NACA whelmed that 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 well so when you go back far enough and lose it loses its identity it will just multiply into a mess 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 yeah 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 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 enjoy 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 it's a 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 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 OS km they're called because one of them causes cancer the M we leave off the M we put OS and K into the I 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 cuz 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 inventing but jellyfish can regrow excells 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 cause 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 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 a kidney so we've been very careful to not just blast the cell with these factors permanently we've titrated of what we said brought the levels down to very low levels and switch it off when we don't need it but we have given mice 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 AI is a good testing zone because it's it's protected and if there's a problem it's you know it's children 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 you can tease us with well we've actually 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 percent 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 kilometres we haven't talked about any debt tell me what nad is what are the precursors how do I supplement for it so there are a few on the market 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 nicotine oh my driver-side 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 n MN does raise the energy levels of older people and and young people are like up to levels that we think you could rarely achieve even with being a marathon runner that's crazy so just to bring this home for people talk to me about your dad and his end of one experimentation with n MN yeah so my father has been on the same regimen as me resveratrol for over a decade the red wine molecule he's been on that from and longer than me because he had done he was in borderline diabetic type two diabetic and he's also on n MN 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 of the world right now he's travelling around America driving his elderly friend around his friend unfortunately ended up going to the hospital the last few days so my 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 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 this 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 look really promising I got embroiled in a scientific and a a corporate war sogni 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 spend 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 work my way out of bed I thought let's dig deep and see if they're writing 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 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 showed that resveratrol does bind to the pac-man 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 pac-man we can tweak the enzyme just in one amino acid in their protein out of about a thousand that blocks this movement activation it's normally chewing like this what if we add resveratrol to a normal Mouse it'll do that to our mutant mouse it's this and which is better or the rapid munching rapid munching is better okay as the rapid was what 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 in 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 is working on some 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 resting so that will be the punctuation mark the fu will arrive but but interestingly the world has moved on mmm all right well I'm left to clean up the pieces right yeah so and when you say the world has moved on talking about people like me who just assumed that it was garbage and that it's not real and right okay so you've said that the only supplement you take is vitamin D so how are you getting resveratrol in the system is it a drug they have to have it prescribed well I'm taking resveratrol I have and would we call that a supplement sure and it's commercially available it is if it's a legitimate seller and it's 98 plus percent pure that it seems to be similar to what I take and ballpark how much do you take I take a teaspoon into my yogurt that's probably close to a gram every day every day yeah okay resveratrol roughly a gram are you taking n mm or is n MN or is it just your dad both of us okay and then 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 have 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 tests to know if what I'm doing is working 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 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% 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 a blood test at least go to your doctor and have a blood test for a good goodness sake you could have your genome sequenced or do something that looks at the the variants 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 not other members family members have variants that predict longevity some don't some have mutations in their genome that are a little bit scary 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 did you a biopsy to do that or can you do it from blood blood test is fine yeah it's so interesting all right where can people learn more about you well so the main site is lifespan book.com that's where you can sign up for the newsletter and buy a copy of the book if you're interested I highly encourage it no thanks I'm also 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 a little fun to do's and 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 died so fast and you know in my view I think it's cruel to have a sentient being that knows it's gonna die in such a short timeframe 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 come further than I thought we 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 gonna have people make one change that would have the biggest impact on their health what change would you have the make well so having read tens of thousands of papers and done this for now thirty 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 malnourished 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 a little lunch at dinner I eat a normal meal I don't gorge myself because that'll trigger all these defensive pathways that will 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 thank you so much for being here 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 a man that was [ __ ] awesome thank you everyone you all know how much what you eat and drink matters literally what you consume affects you on a cellular level and dramatically influences your overall health teas been shown to naturally boost energy levels and provide immune system and gut health support and given what lisa has been through I can tell you firsthand that focusing on your gut health is critical so you can also contribute to mental performance and may even help it longevity you had me at hello with mental performance and longevity Petey makes some of the most convenient easy to use healthy teas on the market peak teas are made from organic high-quality leaves and ingredients from around the world and peak teas deliver 12 times more antioxidants than any other tea PT's are also triple toxins screened for heavy metals pesticides and toxic molds and my team here swears by Petey they love this stuff the guy behind the camera is literally fist pumping right now because he drinks so much of this stuff peak tea packets are super convenient they dissolve in hot or cold water and are perfect for traveling or the office or when you just have to grab something on the go and right now you can get 17 percent off their teas plus free shipping by going to peak T dot life forward slash impact again that's peak T dot life slash impact and peak is spelled P I q ue go there now to get this special discount and check out the description below or just click the link and get your peak tea today check it out guys enjoy and be legendary take care 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 gonna get weekly videos on building a growth mindset cultivating grit and unlocking your full potential

Channel: Tom Bilyeu

Views: 3,384,969

Rating: 4.8880711 out of 5

Keywords: Tom Bilyeu, Impact Theory, ImpactTheory, TomBilyeu, Inside Quest, InsideQuest, Tom Bilyou, Theory Impact, motivation, inspiration, talk show, interview, motivational speech, David Sinclair, Health Theory, Aging, information theory, epigenome, Joe Rogan, stress, life extension, nicotinamide mononucleotide, dietary supplement, fasting, reverse aging, whales, life expectancy, food chain, lifespan, metformin, mitochondria, exercise, cold exposure, nmn, nad, resveratrol

Id: IEz1P4i1P7s

Length: 49min 41sec (2981 seconds)

Published: Thu Sep 19 2019

Reddit Comments

[u/[deleted]]

The comments on that video suck. "Just don't stress and avoid sugar guys!"

Do people even understand what this field is supposed to do? The whole point of the research is to find a way to go BEYOND what any human can do even with perfect genetics and lifestyle.

Exercising, eating right, not stressing, etc. Helps a lot within a lifetime for good aging but its not going to take you to an age that hasn't been reached in eras before now.

We need to focus on the things we can't control even with good decision making.

[u/Griffin90]

hi guys i didnt know where else to post this. Please check out the above video, if you have not already. Its a great and informative, and quality visual video of David Sinclair being interviewed by Tom Bilyeu. Also, i HIGHLY recommend watching this on an HD tv or big screen. i enjoyed watching it on the smart tv youtube app to watch the whole thing.

its a great video and indepth, of almost nearly 3 million views!!! I feel that the Longevity movement is really starting to pick up steam.

[u/GradStud22]

I first saw content from this Tom Bilyeu person earlier this week and I was not really impressed. He was interviewing Richard Dawkins and there were so many nuances that Tom missed when he was attempting to engage on a variety of topics with Richard. Kind of like a 1st year undergrad trying to impress his professor but doing a terrible job with his misunderstanding. The professor, meanwhile, is too polite to tell the enthusiastic pupil how utterly mistaken they are.

I realize this sounds like gate-keeping, but there are some real downsides to having non-academics interview academics about anything at all that isn't personal or simple.

ANYWAY: This video might still be entertaining/informative/worth your time, just suggesting that you manage your expectations before delving in.

[u/ShornGoopter]

Man these guys must have figured out longevity because they think I have time to watch an hour long video

[u/maccasgate1997]

Just a reminder that sinclair is 50, he looks 30

[u/Griffin90]

I shared this video because it has HD high quality cameras of when it was filmed, and was done in a professional studio, with multiple cameras. Generally during covid, a lot of the aging interviews I have seen have been low quality such as webcam skype or zoom interviews.

Also you guys as an update, wow thanks for all the discussions and meaningful comments and the thumbs up. The feedback from the community on this thread has beat my expectations.

Lastly, I know that some people here are not happy with the pace of aging research progress for the last 10 years. Hear me out: it could be a lot, lot worse!!! We could still have been a fringe or dying movement, but instead the longevity cause is showing strides in progress and growth. All you have to do is go on youtube and do search queries like this: david sinclair interview / aubrey de grey interview / longevity life extension research. I think you will be pleasntly surprised that a ton of videos have hundreds of thousands and millions of views!