David Sinclair Is Extending Human Lifespan | Rich Roll Podcast

[Music] get your nad levels up you can do that with being a little bit hungry you can also do that by restricting the total amount of protein that you bring on board so eating a lot of steak would be the worst thing you could do never exposing your body to any changes in temperature it's probably another thing basically everything that makes your body happy and sedentary and unstressed is bad for you and the reason is that you're not engaging your survival circuits but now we can kick those survival chains into action by putting our bodies under a bit of stress or mises or eating plants with those molecules that signal stress we call that Zeno hormesis and that is right now with the exception of some clinical trial proof that exercise and dieting is really the best thing we can do for our bodies exercise is a treatment for the body that actually puts the entire system in a state of defense and so it's less about getting the blood to flow and more about getting your tissues to act younger and that's really the huge benefit that you get from exercise that's David Sinclair and this is the retro podcast [Music] the rich roll podcast here's a couple uncontroversial facts everybody grows old and everybody dies but is this actually set in stone does it have to be this way what if we thought about aging as a disease as a curable disease and what would you do and what would the world look like if we could suddenly live to be 200 plus years my name is rich roll I am your host this is my podcast and this is but a few of the topics we explore today with one of the world's leading scientific authorities on longevity aging and how to slow its effects David Sinclair is a professor in the department of genetics at Harvard Medical School he's co-director of the Paul F Glenn Center for the biological mechanisms of aging he obtained his PhD in molecular genetics at the University of New South Wales Sydney in 1995 and worked as a postdoctoral researcher at MIT where among other things he Co discovered the cause of Aging for yeast David is the co-founder of several biotech companies he's also the co-founder and coach Eve editor of the journal aging his work has been featured in a variety of books documentaries and media including 60 minutes Nightline and Nova he's also an inventor with 35 patents to his name has been lauded as one of the top 100 Australian innovators and he made Time magazine's list of the 100 most influential people in the world finally he is the author of a new upcoming book entitled lifespan the revolutionary science of why we age and why we don't have to which comes out September 10 and is currently available for pre-order check the link in the show notes to check that out if you enjoyed my episode with dr. Valter Longo a fellow brilliant warrior in the longevity space we mentioned him a few times today that was episode 367 or if you happen to hear David Joe Rogan's podcast a few months ago which was great by the way then I'm fairly confident that you're gonna love this one so this is a mind-blowing conversation on everything ageing longevity the scientific mechanisms that contribute to biological degeneration and the hard work that David and others are devoting to both better understanding these mechanisms as well as learning how to prevent and even reverse them I want to say upfront it's not just about living as many years as possible but more about how to live as vibrantly and as energetically as possible for as long as possible that's really the goal here I should also say that this one gets pretty deep in the weeds scientifically which is of course perfect for the geeks among us but it's also grounded in practical takeaways for everybody in addition to being a lovely guy David is a true pioneer it is an honor and it is a privilege to share this brilliant man's work and wisdom with you today so without further ado I give you dr. David Sinclair good to have you here thank you for doing this things are having me on I'm excited to talk to you this is a subject of personal interest of course and I think interest of everybody and the work that you're doing is really not only fascinating but obviously revolutionary or potentially revolutionary so first off thank you for the work that you're doing and I look forward to exploring this with you I think a good place to start would be just sharing a little bit about what got you interested in this field to begin with like why longevity why ageing anti-aging yeah sure I think we're at were all the same when we're about the age of four or five we realized that we're not going to be around forever and and even scarier for a young kid your parents are gonna die and your grandparents gonna die and your pet and cats gonna die so I remember going through that very vividly my grandmother who essentially raised me was a very honest person and she would just tell it as it is and she said to me as a four year old yeah yeah I'm not gonna be around your parents gonna die your cat's gonna die and you're gonna die in on that's a bit of a shock to a four year old who you know you've probably still believed in close at four it was brutal and that may be the turning point in my life but what most kids do and it's been well studied is that they bury that thought it's just too sad to the men it's distracting to dwell on that every day of your life so we actually typically forget about it by the age of six or seven and then it doesn't emerge till we get into our late 40s early 50s and we think okay maybe there is no such thing as immortality but now up until then most people don't even think about it I feel like we still don't really think about it we certainly don't talk about it and death is almost a verboten subject and our exposure to the reality of death and aging in its most you know late in mature forms is something we do our best to whitewash and remove from our field of vision yeah I agree with that and it really takes a lot of courage to be able to think deeply and ponder your loved ones mortality and your own and so I also I don't think about it too much myself though I probably do think about it more than most but seriously I think if all of us right now would consider what they have right now and losing all of that and most likely not seeing most of these people ever again if any of them I mean that's a pretty sad thing and I don't mean to depress everybody but that's something really worth appreciating that we are here right now most of us are healthy but that will not last mm-hmm yeah I feel like we we all intellectually understand that to be the case but I think there's something innately human about being in denial of that truth in order to kind of get through the day like on some level I have this signal in the back of my mind going yeah I know it's gonna happen but yeah I might just evade that somehow I think I'm gonna get around that yeah well that's what we do that's why we survive as human beings it's pretty cruel thing to have a species that's conscious of its own mortality it's not a happy thing and most animals actually as far as we know all animals except us go through life not knowing that they're gonna die mm-hmm and that their their family's gonna die but we are burdened with that but as a coping mechanism and and I believe that it's probably evolutionary wired into our genome that we don't think about that because people who did always worry about dying that their tribes probably died out thousands of years ago right well it can be it can be paralyzing - and you talk about this in that you were nice enough to send me that introduction to your new book that's coming out at the end of the year and you you talk about your grandmother and the impact that she's had on you and her sort of lifestyle antidote to this ethos of living your life in accordance with a ticking clock right that she wanted to live this joyous I mean she sounded like amazing right she's living this joyous childlike existence you know until her body could no longer keep up with her spirit right well I as a young kid she was still in her 40s she had my father when she was 14 15 and so that that allowed her to be very young as a grandmother but she was also mentally young she was vivacious it's she's one of those people where you you know that she's got so much energy she can't contain it so she's she came from Hungary she escaped Hungary after 1956 when Russia cracked down on a revolution when his far away from Europe as she could which was Australia Sydney is where she settled and why where I grew up uh and there she felt free she was oppressed for most of her life with rape and pillage going on and she got to Australia and everyone had enough to eat and they had money and they had sunshine and she just loved life and so she was one of the first people I hear to wear a bikini in Australia and she got taken off Bondi Beach for in the 1950s wearing one of those it's incredible to hear that knowing what I you know knowing what Bondi Beach represents that she was like the first person to wear a bikini on that Beach and got chastised yeah these days you get chastised for wearing a top yeah if you're a woman but yeah she went lived in New Guinea with the natives for a while and hung out there by herself my father had to go get her because she was probably drinking a fair amount she says she tasted human flesh up there with the cannibal so that's pretty big thing for a woman to do that in the 1960s yeah so she was great she raised me to just love life to always stay young and she says grown-ups ruin everything stay young yeah she had this mantra this a melon poem rain about maintaining your your six year old self throughout your life that's right now we are six and she would read that to my brother and me and she would just say make the most of your life stay young don't listen to the naysayers adults are mostly naysayers and leave them leave a mark do what's good for Humanity she said she was a humanist at heart even towards the end of her life a declared humanist and so her goal and my goal is the same which is nothing matters except making the world a better place after you've been here profound especially given that so much of the work that you do is at the cutting edge and it's impossible that that's not going to ruffle feathers and create you know a cadre of naysayers who are trying to take it down a peg well yeah I mean it hasn't been an easy career even from the outset has volta long ago and your shorten rightly said it was rough in the old days studying aging wasn't even considered a true science but like most careers if you try to push the envelope and say things that others have never said before you will have people who try to pull you down but it's uh you know I'm pretty stubborn and I keep my eye on the goal which is to help humanity so these daily fights and and things don't really get me down so much right so your grandmother has this profound impact on you and you're a young enterprise University student in New South Wales and it from what I gather there was sort of one particular lecture that kind of turned things for you that got you out here to the United States well there was a prior to hearing the lecture I was I remember sitting playing cards with my friends and that I didn't try that hot in college or or in school mostly with playing cards and drinking heavily but I do remember one moments telling them all do you realize we're probably the last generation to live quote unquote and natural lifespan and others in downstream of us our descendants are going to live a lot healthier and longer lives than us and we've been born one generation too early do you realize how sad that is and they just went yeah deal the cards David shut up but that stuck with me and so when I heard the lecture from Lenny gurantee who was an MIT professor still is he came and he talked about a project that had just started up in his lab over in Boston to study yeast aging same yeast that's in bread and beer and I was studying yeast for my PhD so I knew yeast intimately there were my friends I would look at the mother microscope and what he told me was they age and I didn't know that most people don't know that yeast cells get old they get fat they get slow to get sterile did you know that there are little creatures and they're a lot smaller than and we are but they have the same struggles through life they have to find mates they breathe and so I thought that was a wonderful way to start studying aging because if we can't figure it out for yeast we've got no hope figuring it out for humans sure so that begins this lifelong journey this exploration into into aging and longevity so before we embark on on that let's define our terms I mean what is aging from your perspective well I've come to the conclusion that aging is a condition I will be bold and say it should be declared a disease and that often strikes people most people as ludicrous but but let's to do some thought experiments here one being if if I was to tell you rich that I just found your real birth certificate okay you say well what is it now I'm telling you unfortunately you're a hundred years old are you gonna want to die tomorrow you're healthy you're fit so that the think the point there is nobody who's healthy and vigorous and enjoys their daily life and enjoys their family wants to die so often I ask people about how long do they want to live and the typical answer is I I don't want to live beyond 80 and God forbid 100 and that's because they don't think of people who are old as being anything worth idle yeah right so that that's one aspect on the aging as a disease if you go to the Merck Manual of geriatrics which is the Bible of this field the definition of of a disease versus aging is very simple it's a 50% cut off if something bad happens to your body and you're in a minority in the population that's a disease something worth treating but if it happens to 51% then hey that's natural that's just aging we should just deal with it that's what God gave us and that's ridiculous you know if you're off by a fraction of a percent its aging by that argument diabetes and heart disease are just conditions of life given how many people are succumbing to these diseases well heart disease is about 40% so that's borderline right what was 51% who might just say hey too bad that's aging uh-huh yeah well dis-ease right it is a you know a diseases is a condition in which your body is out of balance in which there is a lack of equilibrium and processes are not you know functioning properly so by that argument it makes perfect sense that you would qualify it as edge well if we can call it whatever we want you know it's it's our world we can create it ourselves and there so there's no law that says aging is not a disease just as there isn't a law that says it is a disease but what do we choose to call it really determines how we go after it how we classify it and classifications have a big impact on regulation and right now there's no country in the world that considers aging a condition that can be treated so even if a doctor had a pill that could treat aging that doctor could could but but it'd have to be off-label prescribe a medicine to help you that's crazy that's really crazy that probably the best thing a doctor could do for you is to give you a medicine that would prevent pretty much all chronic old-age diseases but right now that's not possible because of the regulation but we don't die of old age we die of diseases that are precipitated by declining well-being right I mean how does that how do you think about that all right well let's take cancer for example that if you smoke it increases your chance of getting lung cancer by about fivefold and we all we worry about that you try to we spend billions of dollars on on trying to treat cancer and prevent smoking getting to the age of 60 increases your chance of cancer by a thousandfold aging is the root cause of by far orders magnitude of all of these diseases that we eventually get they're not separate things aging is what caused these and how we need people do you know that get heart disease and Alzheimer's in their 20s very few the reason is because the body is young enough to fend its fend off these diseases so my approach to this is that if we can figure out why we get old and how to reprogram the body the cells in the body to be young again we won't get those diseases and even if we have the disease those diseases the body can heal itself like we were 20 again mm-hmm okay so then when we age what is actually happening on a cellular level all right so let's go back just fifty years to set the stage of where we are now because it's pretty exciting times 50 years ago let's go back to the 1950s everyone was excited about radiation or scared probably is better way to put it and there are a lot of theories that were put out so Leo's Leo Szilard Peter Medawar came up with these theories about the mutation hypothesis that we lose our genetic information mutations occur and they accumulate during our lifetime and that's what causes aging and mutations largely occur by radiation that were exposed to it's like a breakdown in the structure of the DNA right right so you lose the information in the genome but what's Happ two things have happened eat just in my lifetime first of all that idea that mutations themselves cause aging has been largely disproved you can make mice that have loads of mutations you can knock out their ability to repair these things and they don't get old they live a normal healthy lifespan hmm that's just one example of a whole little live litany of examples of why that theory from the 1950s is in my view most likely to be not as prominent if not just downright wrong this big thing that happened early in my career in the 1990s was the discovery that there are control genes that control our body's health and longevity and so single genes control health so it's not as complicated as we once thought you can make one mutation and an organism whether it's a yeast in a case of my working voltar's Cynthia Kenyans done worms these organisms live a lot longer ostensibly by mimicking fasting calorie restriction and exercise and that was a big deal that was a paradigm shift in thinking there was a lot of debate an argument we're all over that now we all agree so essentially it's just so I understand there are specific control genes that you can identify and when you just tweak those it has that downstream impact that you're seeking right so the analogy would be you've got your your body is a car it wears out but what we didn't realize until the 1990s what that but there were there were body shop repair people who go in and they constantly fix you it's just that as you get older they become decrepit themselves and they don't work very hard and we've now got these genetic and increasingly pharmacological ways and dietary ways of getting them out of data earlier in the morning and fixing your body but then the next big change that happened was that we we asked the question well what are these jeopardy repaired genes actually doing downstream to to keep the body healthy in other words why does calorie restriction work so well and we in the aging field have come up with eight or nine what we call the hallmarks of aging that the underlying causes of aging from Chilam a lost mitochondrial decayed proteins misfolding but I think there's actually one of those pieces of the pie one of those eight or nine that's above all of them that rules them all and this is what I think is that the basis of what I'm calling the information theory of aging and how we came across that's pretty interesting story that goes all the way back to my original days at MIT in the 90s well do tell we'll do so that when I when I got to the to MIT what I wanted to figure out and don't forget I was in a dream team of people so I'm certainly not taking credit for for most of this but one of the things I was personally excited about was trying to figure out why don't ye cells live forever because they're small they're pretty simple and what we and and the team for sure deserves credit for finding was that there's a set of genes in yeast cells and also in our bodies as well though at the time we didn't know it that sense the environment so when a yeast cell is hungry or it has too much temperature change and make it hot make it really cold or you subtract out some amino acids it will live longer and that is because it's activating a set of genes called the sirtuins and their culture tunes because their first yeast gene was called sir - now what's key to this whole information theory is that sir - is an acronym stands for silent information regulator number two the number two doesn't matter but the silent information regulator is a really big deal and we didn't understand it at first so just a little bit about genetics silent information is essentially a gene that switched off and stays off and in yeast that's the genes that control whether a yeast cell is a male or female so to that gene was known already to yeast biologists in the 1980s to silence genes to keep them off and what the lab that I was in guarantees lab discovered is that if you mutate these surgeons or to answer three so four genes the yeast cells live longer hmm we didn't know that a silent silencing gene would have anything to do with longevity we thought that we'd find an antioxidant gene or something like that or a mutation fixer but out came the silencing what we now known is that know as an epigenetic right regulator and that was that blew everyone away but it was very confusing why would a gene regulator have any impact on longevity but what I think now is that the major cause of Aging is a loss not of the genetic information but the epigenetic information of the body so explain the difference between genetics and epigenetics right so genetics is really easy it's just the atcg code in in the DNA strand it's digital information instead of being zeros and ones it's four letters mmm chemical letters and that genome is split up into various little sections that we call genes that typically make proteins and they take care of us but what we haven't really talked much about in the public is the epigenome because in part because it was much harder to study we've only just got the tools now to read the whole epigenome but really put simply if we could take a journey inside the cell and then delve into the nucleus where all the DNA is we wouldn't see it just flopping around the DNA strand is very tightly packaged in other proteins called histones and those histones can be tightly bundled up with the DNA basically DNA wraps twice around a histone and then moves on to another one like a bead on a string and those histones come together very tightly to silence genes so that's what the sirtuins do they they bundle up the genes so that they get switched off or the histones might be spread out and they allow the cell to read the gene and that's how a cell as all these jeans should be on when we're young and that cell should be a neuron and that cell should be a liver and that's what we call the epigenome it's the system that controls how the DNA is packaged and says to the cell these genes should be on and these genes should be off essentially the expression of the gene whether it is expressed or not expressed right is a function of epigenetic it's really it that's true but I put it in different terms than other scientists that I know of because degen DNA is digital the epigenome if you look at it is actually analog and an analog information is extremely subject to noise over time the main reason we switch to digital and so the epigenome the problem is that it's it has to be analog because even in the first life forms that had an epigenome they need to change their gene expression in response to what we eat so the time of day whereas the genome doesn't change essential right and so this analog system had to exist but being analog means that it's very hard to copy it's also very hard to maintain in a pristine state over a period of two weeks for a yeast cell or 80 years for a human and so I'm fairly convinced given the work we've done over the last 10 years a lot of it unpublished that the reason we age is that it's the analog information in the body that's lost over time not the digital in the same way that a compact disc has digital information and if you scratch it up you lose the ability to read the right songs at the right time right that's super interesting how does that square with this definition of epigenetics that's out there that's a little bit more kind of woowoo ephemeral this idea that you know you had a great-grandfather and he suffered a certain trauma and that is expressed in your you know psychological behavior in 2019 isn't that part of the epigenetic conversation it is it absolutely isn't so the epigenome I think is even more interesting than the genome which gets all the attention as the epigenome doesn't just tell your cell how to exist at your life and whether it should stay a liver cell or neuron but it also you can pass epigenetic information from one generation to another mm-hmm so a yeast cell was stressed during its lifetime its daughter will also be there at that address and we know that happens to us as well we've done some experiments in my Sydney lab at the University of New South Wales where we we stress the mother or we make her fat or we make her hungry and the offspring in the case of the the fat mother are prone to diabetes because of the epigenetic trans programs so fastly but the good news is that we've now because we know this and how to control the epigenome somewhat we can now treat those offspring and prevent them from getting diabetes mm-hmm that's wild so controlling the epigenome polishing that compact disc getting the body to reset the epigenome to being healthy and young is what I'm focusing intensely on right now and so to extend that metaphor keeping that that compact disc super polished making sure you know making sure the integrity of the analog aspect that epigenetic aspect of of you know the aging mechanism is running properly involves this sir - right like I'm let's get back to back because that's where I'm starting to like yet quite understand what you're saying okay so sir - is sitting on these jeans bundling them up and making sure that they stay off so let's say you're a nerve cell your pristine young nerve cell you're in a fifteen year old or a 20 year old young kid the your sirtuins particularly three main ones there are seven of them three of them are doing this they say okay all of the the neuron cells you don't want to express a liver cells so let's keep that quiet for the rest of your life that's what these are two ones do but the problem is we find is if the that the sirtuins have other roles besides keeping gene silent they actually are very important particularly number sort one insert six they are involved in repairing damaged DNA as well and the worst type of DNA damage that they have to repair the most fatal for the cell potentially fatal is a broken chromosome at what we call a DNA double strand break and in yeast when I was back at MIT we had a paper in the journal Cell that said that these sirtuins they moved to DNA breaks when they needed move away from the genes that they should be silencing mm-hmm these genes come on temporarily probably as a stress response and then they have to repair the break and then they hopefully go back to where they came from the problem is we found in yeast and we are finding this also in mammals is that they don't always find their way back to where they started and so you over time you lose the youthful gene expression thanks to the look miss localization of the sirtuins and and other proteins not just soar towards but there are bellwether of this CD scratching so they're sort of like ambulances or you know the california highway construction crew who's been dispatched to a certain you know pothole or problem they fix it but over time they start to the radios don't work on the way home and they get lost that yeah I got better myself right and and the worst part about it is that it's it's a positive feedback in the sense that now you've got some these pothole workers who've lost their way and you're not fixing the potholes as well haha and you get more and more potholes which distracts these workers even more and this is why after age 40 particularly after age 50 you get this massive decline in health oh and we have actually engineered yeast cells and a mouse in a way that we can distract those Sur proteins and and see them age more rapidly essentially create some few extra potholes and distract those workers and we we actually do see that aging goes faster but the good news is interesting um for the for the mice anyone who's worried about our animals we have ways of reversing that now mmm-hmm and one of the things that you've discovered in the search too try to create greater functionality here is the impact of something called nad on this process right exactly so the sirtuins turn out to be enzymes and very special enzymes what think of them as the the crew that that's directing the pothole repairs and you know like I said the bodyshop repair people they literally modify other proteins to do a better job at repairing the body and by modifying that they remove chemical groups called asset ills and in doing that they can actually have a much bigger impact on the body than just one enzyme alone they control hundreds of other repair enzymes but they only work they can only remove that little s atul piece of other proteins if they have nad around technical code in terms we call it a co substrate but that just basically means if you don't have any d the sirtuin enzymes they can't silence genes they can't repair DNA and by the way without nad you're dead in a matter of minutes almost like the key sustenance for sirtuins exactly but nad is a pretty boring molecule at least it was until sirtuins were discovered it's needed for basic biochemical reactions in the body and you can find it in textbooks if if you studied biology in college you would have read about nad and before we came along people have really forgotten about nad they said it's a housekeeping molecule we've you know everything we need to know about any D and then along come the sirtuins and it's Wow nad isn't just there to keep us to do chemical reactions it's sensing how much food we eat preferably less how much we exercise preferably more and even things like hot and cold and in the yeast cells turns out if you stress those yeast cells a little bit with those treatments you turn on the ability to make more nad for the sirtuins do a better job and so now you can have the sirtuins keeping those genes silent and also repairing the DNA and finding their way back home much more easily so nad is the best way we know of to keep those her to ins active and able to cope with that repair and silencing process and as we age do we develop a deficiency of nad yeah we do that's the sad thing is that when you measure nad and animals and also in humans we have about half the levels we once did once you reach some almost 50 now I haven't measure INAT levels but I would say it's probably based on the studies about half of what it was when I was 20 which is a scary thought this is a molecule that's needed for life it's we now know it's a molecule needed for sirtuins but we've also found that many diseases are associated if not caused by low nad levels and so I think one of the approaches that the we're taking has a lot of promise which is to give the body extra precursors to nad to raise those levels back up to youthful levels and let the sirtuins do their work and this is the N and a man that's an amine any men don't confuse it with MMS that they're not as good for you probably how I know it's tasty it's actually it I have tasted it in a man and it's pretty sweet it's it's a not a bad molecule so often people wonder what is nm in its stands for nicotinamide mono nucleotide actually the nucleotide part of it interestingly is related to DNA it's one of the early molecules that formed on the planet when we first had life but anyway in a in a man is taken up by the cells you can eat it you can give it to mice in their water supply it goes into the body very rapidly and the body turns it into nad in one step and that step is what gets activated by stress so go back to yeast for example when we shock the yeast with a lack of glucose sugar or give them a bit of heat or take away amino acids they will make my nad by converting this intermediate into nad and we think that's true for the body as well for our bodies when we exercise if we go hungry we see more nad produced still over time and this is this is a product of hormesis stress stressing the body to create a favorable downstreamers exactly so hormesis is is that the crux of why exercise and dieting is good for you why calorie restriction makes animals live longer and we didn't know that until the early 2000s but all of this came together and then we figured out a for yeast this entire pathway and then we've been working on testing whether that hypothesis in or at least that fact in yeast is true in us as well and so far it looks like it's surprisingly similar to what we learned there right so you've developed this nmn I guess you would call it a supplement yeah supplement product this is something that you take your skin looks amazing there's not a gray hair on your head you're 50 right looking very useful a good ambassador of the work that you do and this is very interesting so by supplementing this you are basically taking out an insurance policy that allows your sirtuins to function the way that they're supposed to without this degrading impact over time is that an accurate assessment of the idea here yes you've got it and so I don't know whether these molecules that I take are going to be helpful but I do know that they're not hurting me as you said and if I'm around no and all my colleagues are old will know something is happening but yeah um what's important I think for your listeners to know is I am trying to get these molecules at least tested if not proven hopefully to work in people and so that requires a lot of time and money and effort right and so there are ongoing clinical trials one of them's run out of Harvard University at the Brigham and Women's Hospital and where early-stage we've just done the safety studies but later this year we should have a readout of what we call efficacy which would be testing whether what we see in the mice some of it is recapitulated in older patients as well and eventually I want this to be a that will treat diseases as well right so yeah so FDA approved the pharma route not the supplement route right it's very hard to straddle both actually I think it's impossible to straddle both and so I've chosen to take the farmer route because I want to be able to have something that is proven to work is safe and I just think that for me is is the better path for me I want to be someone that is not conflicted is not trying to promote anything I never sell products or trying to endorse anything and so people can come to me and or I can give lectures freely and people can know that I have no hidden agenda mm-hmm but you have your hands and all kinds of companies out there you're very enterprising entrepreneurial scientist well I do but there's nothing you can buy from me so there's nothing I'm gonna gain really immediately but I do I do entrepreneurial activities not because I'm I just I'm interested in in the short term gain I want to leave a legacy and so I've had my eye on that goal since I was in my 20s and that goal is to leave a mark and I'm not just satisfied with publishing papers in these journals I want to have a medicine if not hopefully a few of them that will save hundreds if not hundreds of thousands of lives thinking you know forward towards that creates a lot of interesting thought experiments around what would actually happen should your mission come to fruition right so is your mission to to end aging as we know it like what is the specific goal that you're striving towards here well I'm not trying to end aging I'm I don't believe that there's going to be immortality but I do believe that the wave being going about medicine for the last couple of hundred years can be improved the way been going about it has been take one disease at a time and study it and ignore aging and hopefully making medicine to treat that and so we've been very successful as a species making medicines that prevent and treat heart disease for example but what's that's what that got us yeah we get an extra couple of years of life and that's all because other diseases are still coming along right behind but we end up spending those years with other chronic diseases and we're actually spending longer times of our lives in a 6-day than we used to and that's really to me it's it's something you wouldn't even wish on your worst enemies is to extend life but not extend health right if we were to if you were to identify like the the sort of ultimate age that we could perpetuate I mean what is that is that 35 is it 25 is it 46 like is there a chronological period of time where you think the human mechanism is functioning at its peak and that's where we we could we should just sort of lock it in yeah well I don't know I'm 50 and I feel like I'm still 20 so I'm not seeing any decay so any any age between 20 and 40 50 is fine with me aha I mean clearly the athletes lose their ability to perform it at that level but you know I'm I'm a mental athlete and in my brain is far better than it was even a year ago so I'm I'm I definitely don't want to go back in time put it that way but what's interesting about athletes is we're finding that because we know a lot more they know a lot more about how to keep their body young part you know popular what they eat how they live we're seeing these athletes also actors take Tom Cruise looking a lot and acting a lot younger physically as well then what we had just a 20 30 years ago previous generation yeah are you working with Tom Cruise behind the scenes no not Tom Cruise no no but somebody else somebody else you don't want to say well there haha there are plenty people I get to meet yeah it's a fun job I put it that way right right right well all these billionaires who are injecting themselves with young people's blood there's certainly a lot of interest in youth and longevity amongst the well healed so I'm sure your you've got you know a rolodex of fascinating people that are trying to get your time it's true and I help as much as I can and often I'm asked well David you you're working on these medicines and how come only super rich people get access to you would you first of all that's not true I reply to every email that I can but also it's similar to the Wright brothers that the phase that were in now with with Aging in that we know that we can build a glider it's flying we've seen that we know how to do this it's just a question of strapping on an engine and taking off and flying around and we're building that but that takes entrepreneurs it takes investment mm-hmm and certainly the the mm so that the 19th early 1900s required millions of dollars of investment and who are the first people that were flying was probably wealthy people people who knew others and it's not so much elitism it's just that's how all technology rolls out and so the I see this as going rapidly as possible to people and my mission to roll this out to everybody on the planet and not just wealthy nations I've pledged to make the drugs that I'm making available to everybody on the planet as soon as possible well it is true that people are looking you know more youthful in their later years and we're seeing athletes who are performing at a very high level at ages that people would have thought was impossible you know 15 years ago and that super interesting and I would imagine that's a function of a multitude of factors including you know people have to these athletes have to make there has to be a way for them to make a living so that they can continue to do this but one of the things that was super interesting about the studies that you've done on mice with nad and nmn was the increased blood flow that was created that led these mice to have like this something like a sixty to eighty percent boost in their ability to like be on a treadmill and and produce you know an athletic output I mean I read that I was like wow like what's the athletic implications of that is this doping or is this like cool like what's happening here well it it it's certainly cool science whether or not it's it should be considered doping or not I'm not really sure because we're talking about boosting a natural molecule that's in your body anyway it's increasing blood flow right it's like it's improving like your vascular delivery system it is so let me explain how that works what we discovered was that the sirtuins let's go back to those guys again in the lining of your blood vessels they're not very active as you get older and one of the main reasons that you don't respond well to exercise you know if you're 70 or 80 maybe even younger and you exercise you still aren't a super athlete because they're what we think is the major reason one of the main reasons is that the lining of your blood vessels the sort Owens 31 is the main gene isn't doesn't have enough nad around and what was remarkable was that we could treat mice with the sentiment molecule just give it to them in their water supply raise the nad levels back up to young levels in the blood vessels and now we had old mice that first of all they they acted as though physically they'd been training but they hadn't been but also if we gave them animun on top of exercise they became super athletes beyond what exercise alone could get them as wild and it it's super cool as well because the one of the major causes of disability and frailty as we get older even into our 60s and 70s why do we feel tired when we wear older is because we don't have enough for this blood flow and very few people have ever thought to figure out why that is and so that's why we jumped on that and and so imagine it's great for young people as well I think it's it could keep people in tip-top shape especially people who cannot exercise as much as they want like myself who types for a living but more importantly far more important than people like me is those people who are already frail you know people who are in bed or who are who cannot really walk very far we give them potentially these nad boosters as we call them let's call it that MIB 66 which is the drug form of what we're developing give it to them for a few weeks and they hopefully what I hope is we'll see as they have the energy that the new blood flow they can start to walk again and that's a virtual a virtuous cycle a positive feedback in a good way so that they get out of bed they walk they get more exercise and get back into mobility because it's the lack of mobility that ends up killing yeah yeah yeah and what are the implications on arthrosclerosis like is it it can it reverse arterial damage and create you know greater plasticity like how does that work oh we haven't just Adana men on that but others have and we find that this sort one certain is extremely important for protecting the the cardiovascular system from from plaque as well as keeping it youthful and so there was a study by Doug seals at the University of Colorado just to mention a much an independent study they gave nmn two old mice and similar to the way we saw new blood vessels growing they saw that the existing blood vessels had had much better plasticity and resilience as well and so the hope is if we can get these molecules to be super potent and targeted to the right part of the body I will have all of those effects on people and just this also have implications for mitochondrial decline because isn't that another key aspect of aging well it does and just to preface that often what I'm saying sounds too good to be true because it's pretty awesome every time people ask me that yeah it does that it cures this just that well first of all we're still in mice we don't know if it works in humans but what we're gonna figure that out in the next year or so but yeah you asked me about mitochondria we've published these are all cell and science papers so these are top studies these aren't just off the right kind of stuff so a lot of work has gone into them what we showed in mitochondria was raising the levels of nad in cells fixed what was a really curious defect that happens as the mice got older so what was that but we found is that the organelles the different parts of the cell that have different genomes so we have the nuclear genome our chromosomes but also have mitochondrial DNA inside those mitochondria huh we found that those two genomes were not communicating as the mice got older and so we called it genome asynchrony and it's essentially if you want to put into a some sort of a an analogy a metaphor it's as though you when you're young and you're a young couple the the people get along they're in a small apartment they communicate well but by the end of it they can't can't stand each other they're not communicating we see that with the mitochondria staring at their phones at dinner not talking to each other yeah I mean imagine how bad that is for our bodies and we so we figured out why that occurs and traced it all the way back to the lack of nad so by replacing the replenishing the nad mitochondria started communicating the new clues that mitochondria said to the nucleus hey give us some protein like you used to when we were young and that completely restored the function of those mitochondria in the muscle and so we called that reversal of aspects of aging in fact those muscles that we looked at in those mice those mice were two years old and within just a I think it was two weeks of treatment they were just like a young Mouse Wow the implications are insane for something like this I mean that's amazing are there any negative consequences of this I just feel like there's a there's often a hubris in humans with this sort of thing in our reductionist scientific method to zero in on one thing and we see this positive implication and we are blind to you know all these other aspects of what goes on because it's a holistic machine you know there's a lot going on just you know there's a lot of dominoes that are stacked up against each other here that's right and part of the problem I think with medicine and and why pharmaceutical industries had trouble making drugs with without side effects is that they are first of all that they're using synthetic molecules that the body has never seen in part to patent protection and supercharged molecules but also that the problem is that they're intervening in aspects of the body that normally don't change and it would be like revving up a Mini Coopers engine but not making sure that they have the right gearbox and tires to deal with it and so the approaches we take we try to change those parts of the body's body that changes naturally mm-hmm when we exercise or when we diet and that's why philosophically I'm less concerned about side effects because they're really just replacing what we've lost with age similar to the NAD levels but are there side effects well we haven't seen any we've just been giving nmn to mice for the last year or so we haven't finished the study and thank you to all of the the people online who crowd-sourced fund that start fund in that study but we're already seeing a lifespan extension in those mice and so that's exciting and every time you see a lifespan extension in the mice it's hard to argue that we're hurting them now maybe there's something going on but maybe they did pressed or something but other than that they are otherwise perfectly healthy now again these are mice we haven't treated humans so that's why we're doing these safety studies I don't stay up at night worrying about the side effects given what I've seen over the last year in many years in many labs across the world there have been thousands of animals treated with these molecules nothing that rings alarm bells but if you wanted to push me right rich says David you got to come up with one thing that you could see might be negative it would be blood vessel growth if you have a tumor already that needs a good blood supply and we grow more blood vessels that would not be good and so that's actually why we've done a couple of studies in Mouse in Mouse cancer models and given them an MN and the good news for the listeners is that we've not seen any deterioration or an acceleration of those cancers and in one case we saw that the tumors grew much more slowly then without the nmn but that doesn't really mean that it's perfectly safe so that's it's one of the reasons why I'm doing these clinical trials is that first of all I want to be the first person to know if it's unsafe my family definitely wants to know that but I want to be able to sleep soundly knowing that I'm not doing any harm to anybody yeah me being a non-scientist I've been operating under this idea that you know part of aging is a result of free radical damage and that we should be eating a lot of antioxidants to combat this free radical damage and when you were talking to Joe you were sort of dispelling some aspect of that conventional wisdom so can you explain that a little bit yes if free radicals are part of the story but really it looks like just a minor part of it so free radicals will will cause DNA damage we know that and it'll cause those DNA breaks that scratch the CD so that I'm not saying that they're not completely that they're irrelevant but amongst Iselle oxidation so oxidation you don't want it but let's go back to that car analogy I think we've in terms of the free radical idea it's as though we've said hey you know what the windscreen wiper blades are old let's replace those as to fix those windscreen wipers not realizing that that's the least of our problems we've got other things that we could do to keep our bodies healthy and so that and you know there's a lot of studies in in the world now that of where people have tried to use antioxidants and fail to extend lifespan in animals there are some success stories but you can also think of other reasons why those molecules as nth quote-unquote antioxidants have actually worked and one reason that I think is plausible is that those antioxidants that typically come from the plant world are engaging the sirtuins and other survival longevity mechanisms so that they're not only mopping up free radicals but they're engaging our survival systems as well Andres Perez Vera troll would be one of those right so that's what got me started thinking about this but if you look into the the science of this and the literature pretty much every molecule that we take in from plants that has medicinal properties let's say ECG C from T what else our aspirin is also a good example these molecules have so many different effects on different parts of the cell different pathways and so they might activate mpk while they're inhibiting mTOR while they're activating sort ones that cannot be a coincidence that these plant molecules have all the right impact on these longevity pathways it's as though we've I would say the only explanation no take it back the main explanation I think is that we've evolved to sense the plants stress conditions so that we hunker down when we're gonna run out of food there is one other explanation that is that these molecules and plants we make something quite similar but we just don't know what they are yet hmm so there might be a human resveratrol that we haven't found yet right right and and so basically the resveratrol which is that which is an antioxidant is also a plant's stress response to you know some external event right in order to defend itself and make its itself stronger and by taking that in we're having a similar impact on our own cell structure that's exactly right and so we found pockets in proteins that sense how much resveratrol is in the body so oneness sirtuin that I've been talking about has a pocket that resveratrol sticks in and it activates it we know that a great detail down at the atomic level but these other molecules also happen to bind at the right place on these proteins so it's exactly what you said which is that when the plant is stressed it's making its own molecules like resveratrol to survive plants have sirtuins sirtuins have found even in bacteria and I don't think the plants are trying to make us healthy but we use them as a way to make ourselves healthy and we've learned over the last few thousand years or maybe longer that if you eat these types of foods at this time of year and you bottle it and keep it dark and put some alcohol in there it'll preserve those molecules and you'll get some health benefits as well you might get tipsy as well but we've had to do that empirically rather than knowing exactly how it's been working right and it's it's problematic as well because it's not as binary as we would imagine there were all those beta-carotene studies like if you you know if you take base you know super dose with this it will combat all these things and make you healthier in all these different ways but whether it was a bioavailability issue or you know it's like when we extract these healthy you know aspects of a plant and take them in a singular dose it doesn't quite have the impact that it does when it's in the complex matrix of the plant food itself 100% you hit on something that I think about a lot which is so we've been just taking the plain resveratrol molecule but when you drink it in red wine or you take it in it's a natural form all of these molecules are coming with a cocktail that's probably finely tuned our bodies are finely tuned too and also what we find is these combination of molecules are actually synergistic so for example if you take quercetin core settings i'll call it at the same time with resveratrol they will both last longer in the body mm-hmm and by separating these out which we like to do is reduction as scientists we're losing some of that and also that the other problem is that if you're just using a plain chemical like resveratrol of course certain these are fairly insoluble so most of it doesn't even get absorbed it's only when it's in its natural state when it's combined with sugars and in many cases fats that's important to help the uptake and that's why often when people ask me how it's resveratrol would you need to take to have an impact I have to be careful because sure if you take it in its pure form you need hundreds of glasses of red wine but if you drink a few glasses of red wine for a decade not that I'm advocating that but there are some signs that that combination of molecules with the alcohol that helps the absorption could be way better work way better delivery vehicle than just eating a spoonful of rest powder which is like brick dust right right right other than red wine what are good sources of that over his virtual very little is in the food supply unfortunately it's a little bit of nuts and ghost grapes but it's very hard to get the quantities besides in in red wine uh-huh and buying it in powder form I mean how much of that is is just paying for expensive urine versus real impact well so I don't really know that but I do know that that if you take it with fatty food so I take it with you ogre or something that at least will help absorb it that it's very helpful and part of the fat aids with the absorption oh yeah so we've sought levels in mice and humans that were five to ten fold higher with some fat included and actually we had much better results in the mouse studies when we gave them or is virtually in a fatty diet uh-huh and what it what is a what is it about resveratrol that makes it superior to say something like turmeric which is also a powerful antioxidant are they qualitatively different or are they you know can you switch these things out for each other I don't know the answer to that I've actually spent less time studying resveratrol the last decade because of more interested in some of these other well and now we're beyond that as well with that's certainly exciting it's heading it past the clinic hopefully trying to figure out what the scratches are in the CD is is it's a major focus of my lab right now and so I think that what what the future looks like is that we hopefully will be able to take some of these longevity stimulators any man is just one of them of course there's Senna lytx which destroy the zombie cells we've got we've got metformin which are seems to be beneficial so I don't want to you know basically annoy all my colleagues who have spent decades showing that their pathways are important too but that these are mostly preventative what really we want do is get you out - no ninety one hundred hundred and ten healthy but eventually things will wear out things will still decay even with these treatments they're not that good uh-huh even with healthy lifestyle so the new work in my lab is what do you do when you need a a new kidney and you liver or you lose your eyesight can we tell those organs to be young again and literally make it young again the difference between prevention and reversal right basically right you know it's interesting rich that I think I was one of the first people crazy people to use the word age reversal in this field uh-huh it was a shame on you it was not well-received I imagine there's about five years ago now it's fairly common honey it takes a while but you used to be able to say delaying aspects of aging and that was the limit but it's clear from work that we've published and worked we haven't yet published that reversing aging is really easily doable we do it all the time in my lab I mean similar to what you know once you know how something works the answer is pretty simple best analogy is you know Joseph Lister said hey let's wash our hands before we cut off a person's leg or deliver a baby and save millions of lives probably right now a billion lives you know for goodness sakes we solved this with soap same root aging once you know how simple the process is it's not that hard to fix well we all are familiar with this concept of biological age versus you know what's the other one like experiential age like you know how we look and feel isn't necessarily Wed to our date of birth so on some level we have a fluid understanding or conceptualization of aging some people look older and comport themselves like an older person then somebody else who's exactly that same age so clearly there's something happening here that goes beyond just pure genetic blueprint that we can influence through diet lifestyle and some of these other you know factors that you're exploring now yeah so than half some it by some estimates only 25% is determined by your genetic makeup and the rest is how you live in your epigenome control which is great means we have much more control over our lives than we then we thought we did and we see that now that the impact of diet is just incredible what is the biggest thing that we have control over what are the what are the most important things sure well if there was one thing that I could say if there's one thing you could do it would be eat less mm-hmm that's the main thing and I know you've you've had plenty of people right with that Psalter Longo who's you know discuss this at length with his intrument fasting and is fasting mimicking diet and all of that and I know this is something that you practice and are on board with as well so what is going on with either calorie restriction or the way that we time our intake of food that has implications on Aging or its reversal yes so calorie restriction is is the most robust way to prevent cancer heart disease or pretty much all diseases it's been known for since 1916 and then a very classic study in in the 1930s by McCain colleagues so we all agree that calorie restriction or intermittent fasting these days works the question is how and what we've found is that some of the pathways that we study in the aging field sirtuins are a major part mTOR is the other which voltar has talked about on this show these are pathways that respond particularly to how much we're eating and if we eat a lot of food they stop defending our body or telling proteins to defend us and if we less what happens is they get kicked into action and they they do a whole range of things that protect us from disease and even can reverse aspects of aging and so just to focus for a little bit on the sirtuins because we're on that theme when you are hungry you're nad levels go up and so now you're such ones are quite active and repairing the body and they can make sure that the body doesn't lose its epigenomic stability in other words keep those scratches from accumulating over time and long you do fasting over your lifetime the slower those scratches will accumulate and and so we dot exercise as well raises nad levels and your listeners might be wondering why why would exercise and diet turn on these pathways in the first place well what we we think is going on is that in early life in the primordial ponds there were so picture early Earth is Earth's covered in ocean there's these islands and there's little pools and we think that's where life formed this is the cutting-edge science right now in those pools are little strands of RNA that have come together from chemicals from meteorites first cells are forming those first cells need to be able to control those genes on and off so when do you want genes on and off while responding to stress so if there's a cosmic ray coming and hitting and smashing that genome of that little organism it needs to have a system to defend itself to hunker down survive and then repopulate that pond when all the other organisms have otherwise died off this is extremely ancient genes that we have inherited from those forebears of ours but now we can kick those survival genes into action by putting our bodies under a bit of stress or mises or eating plants with those molecules that signal stress we call that Zeno hormesis mmm-hmm you know meaning between species and that is right now with the exception of some clinical trial proof that exercise and dieting is really the best thing we can do for our bodies Wow is there when it comes to fasting is there any indication like I'm trying to get a sense of can you do it too much our people who are doing these 30-day water fasts are they getting any additional benefit beyond somebody who's doing vaulters fasting mimicking diet which actually involves eating you know meals throughout the day or do we still have a lot to learn here well yeah we always have a lot to learn but we know it pick up a lot and more than we did a few years ago what we've found in mice as a field is that and just that came out about a month ago from Raphael to Cabos lab at NIH found that it's it's not so much what you eat but when you eat that's so important for those animals and probably for us as well that doesn't mean that we can just eat whatever we want and and go hungry I think it's a combination of the two things and that's what I do with my own body as best I can but primarily you you need to be hungry a little bit preferably every day but at least a couple of days a week that hunger creates that stress response that this sirtuins doing what you want it does the the buddy shop or pepé will actually get your nad levels up and you can do that with being a little bit hungry you can also do that by restricting the total amount of protein that you bring on board so eating a lot of steak would be the worst thing you could do never exposing your body to any changes in temperature probably another thing basically everything that makes your body happy and sedentary and unstressed is bad for you and the reason is that you're not engaging your survival circuits I call them and how does that square with studies that are coming out about sauna therapy or cold water therapy I mean these are other stressors right that I'm sure are having cellular implications well they are but we don't know a lot I'm unaware of any rigorous studies of cold therapy and or even saunas but we do know from anecdotal and and historical records that even the Romans knew or thought they knew that heat and cold was good for you and you know a lot of northern countries swear by it at least one said once a week you want to go into that sauna and then jump into a cold pool now I I don't know if that works I don't think anybody really know if it it knows if it works but like what I can tell you is it it does fit with the hormesis idea that we studied yeast years ago and what I found was that when you the temperature of a yeast cell it will turn on the sirtuin pathway it'll make more nad give it a bit of what we call a heat shock we do know that if we cool our bodies down we shiver a little bit it will build brown fat which has a lot of health-giving properties as well boost those mitochondria which is always a good thing so that fits with the science so that's why besides the fact that it feels really good and invigorating I think it's also gonna turn out to be healthy as well yeah I think there are some studies that are happening around sauna on you know vascular health and things like that I'm not steeped in it but I know there's certain things that yeah there are some studies I agree with you that there's one of I think it was a few thousand Finnish businessmen who regularly takes honours and they had protection against heart disease apparently it's early days but rich you asked me earlier and I haven't addressed yet what's too much and I definitely think you can do too much of anything and we call you know in hormesis there's this u-shaped curve inverted you so that you just have to find the optimal and that's really tricky not only because it's hard to know if you're overdoing it we don't know what those parameters are we barely know what the biomarkers are if you were to measure them in your blood but also because it's different for everybody that your optimum might be different from my optimum and it's certainly different for men and women and people at different ages so Valter Longo mentioned that you might want to restrict your protein when you're young but when you're older that come back to bite you right so if there's a lot of variables here and it's extremely difficult for us to test one human group let alone all of the different variables well the way I do it is I just overdo everything as far as they may right so that makes a plan yeah right this is the the Zuckerberg way it's a fail fast sure but you know I really think that that overdoing it on you on your physical body so running over doing it with running for example playing some very high impact sports we just know already that those are people who tend to have to have their joints replaced in their fifties my joints are pretty good right now but yeah back's a little creaky you know ankles are a little stiff when I wake up in the morning you know it's like going out and crushing it and putting in giant miles all the time I mean you know this is not a recipe for you know maximum longevity I'm aware of that but I also makes me feel great like I you know there's counter valent counter balancing you know aspects to all of this we'll do you measure your biomarkers do you know what it's doing probably not as precisely as as you would I've had blood work done and my blood work is fine in fact I'm getting it done again quite soon but it's been good I tend to get adrenal fatigue that's like the main thing that I have to worry about because I'm it's just a work hour play hard person in general yeah well if you overdo it you can also be susceptible to infections getting holds pretty badly I never get sick I don't have that problem that's a great sign one thing that's in common with all of the people that live a long time into their hundreds is that they say when I was younger throughout most of my life I never got sick mmm all right well I got that going for me but I will tell you this my my grandfather died of a heart attack at age 54 I'm 52 and I've been plant-based for 15 years and an athlete and all of this sort of thing but it started it started to really occupy a lot of mental space because I very much share his genetic blueprint and you know we look alike we we've made similar decisions in our lives lived our lives very similarly and it definitely has me you know a little more freaked out than maybe it should because of that genetic predisposition to heart disease that runs in my family and just buying things I died to countervail you know to live my life in contradiction to that I know it's it's sort of looming there and so what should I be doing well do you know what genome you have I should have that test it I have no you haven't tested you Gina uh-huh so we have to hook you up with one of my good friends at Stanford you're at Stanford's I know that so it's apropos that you go see my good friend Carlos Demonte yes that the Dean of uh yeah he's got us out there he's the guy he's done some pretty important genomes historical so Kennewick Man that kind of thing right he will help you interpret your genome um you you can have it done at some of the the commercial places if you want that's what most people do it's pretty informative I found it's not just for fun I found that I carry some pretty bad genes and I'm modifying my life based on those and actually to bring it home my wife has predisposition based on her genome for ulcerative colitis and she actually ended up quitting her job and doing what she always wanted to do because she figured that she was going to have a shorter health span than most people and she's too modified her life in her diet and so far so good she's uh I won't say how old she is that wouldn't be polite but at the same age that she is now her mother was suffering from ulcerative colitis and now has no bowel and it's not very great for her um so I think that the the genome is important to know I know some people say that it don't just don't want to know I mean there's definitely part of me that because there's a that sets in motion a series of decisions that you make about your life based upon something that may or may not come to pass so I I definitely have concerns about that well let me tell you a story about myself I had my genome done I did it at 23andme and then I had it done full genome and I found out that I carry a susceptibility gene to emphysema COPD and that my lungs are not very good at clearing out toxins from smoking now I've never smoked on a militant against smoking in part because my mother died from smoking and guess which parent I inherited that gene mutation from from your mother it was my poor mother if my mother had the information that she had after her lung was removed and eventually died from she probably would have quit smoking earlier mm-hmm rather than waiting until she had one long so you can really be empowered by this information and I try to avoid dust I try to avoid secondhand smoke for that reason going back to something you said earlier you said it's important to keep your amino acid your protein intake low so explain why that's important well it comes down to a an enzyme complex called mTOR and it's called target of rapamycin so repre Meissen is a it all started back on Easter Island we had sagal which is uh he was a scientist who went to Easter Island or Rapa Nui which is what's called rapamycin he found bacteria that had his peculiar molecule called rapamycin and he his lab was at Columbia University and eventually he ran out of money and he was told just throw away all your stuff in your freezers and he decided not to and thank goodness he didn't because in his freezer was the organism that gave rise to this rapamycin molecule which is now used to treat a whole variety of ailments mostly immune disorders but possibly even aging and the reason that we're excited about repre Meissen or at least molecules like rapamycin to treat aging is that if you disable mTOR or you give rapamycin which is essentially the same effect what you do is you trick the body into thinking that it's got a deficiency in amino acids so mTOR has been around very long time similar to sirtuins but it's job is to sense how much meat or amino acids a protein is coming into the cell and the body so if you eat a lot of meat what you're doing is you're telling the mTOR system times a great lots of protein don't worry go reproduce grow build new tissue but at the expense of hunkering down and repairing things mm-hmm and so if you're always eating meat and always eating a lot and a lot of protein your mTOR system won't bother to defend you because it'll always be on and the on for mTOR is actually the the anti longevity it's the growth and reproduction versus the hunker down survive mode mm-hmm right so longevity dictates that you want to be doing what's necessary to signal your body to enter into that reparative mode right and that's at odds with when you're younger you want performance gains if you're an athlete you want to build you know big muscles and all of these things that that's all fine but you can't have both it's very hard I would I would say and and people who are who grow fast are have to be extra cautious because their bodies especially when they're young are spending more of their energy on growing than hunkering down and this is just a fact but it's probably depressing to some people that at least in in dogs and it looks also like in in humans that if you've got a highly active growth system a lot of growth hormone it will work against you later in life yeah but you know again a lot of it's in the control of our environment we if you're if you're tall person I'm not but if you're super tall I think it's even more important to make sure that you're what you eat and how you fast and how you exercises is optimal if you want to live the maximum potential I spend I have a lot of friends who get testosterone therapy and can get you know HGH and all of these sort of things and the idea is it's boosting their you know virility and their energy levels and all of that but I can't help but wonder what the implications are on their long-term wellness and well-being and longevity like there's a there's a evolutionary rationale why these things decline over age right well you could say the same about nad that it declines and it's not good to boost it so I think that that that's dangerous to use that argument that just because something goes down it it's meant to uh-huh but there have been millions of dollars poured into clinical studies with testosterone with no benefit to to healthspan and I believe lifespan as well and so in our field we actually regard those studies as somewhat of a failure to deliver and so I think that that the evidence is there that it will give you testosterone probably gives you great benefits if you're exercising you can build up more muscle your more quote unquote virile but it in the long run it doesn't help you and probably hurts you because it's signaling your body that it doesn't need to produce it on its own or because it's stimulating growth in areas that you don't want growth that would be my explanation I don't know for sure but I think just telling the body grow build muscle all the time is basically sending the wrong message for a long lifespan right what about exercise what's happening when we exercise and how is that impacting aging longevity well first of all tell let me tell you what exercise isn't it's not just making your blood flow around your pipes and cleaning them out it's what I was led to believe in the 1970s what's actually going on majorly is two things one is it's activating these longevity pathways in your blood stream and I've mentioned earlier that the sirtuins are a major part of that but it it's also having highly anti-inflammatory effects and it's able to change the way our bodies actually respond to it the environment exercise is a treatment for the body that actually puts the entire system in a state of defense and so it's it's less about getting the blood to flow and more about getting your tissues to act younger mm-hmm and that's really that the huge benefit you get from exercise so why can't we diet and exercise ourselves into immortality yeah that's a good question because I think that these defense pathways are not perfect they don't know how to fully route the scratches polish off the scratches on the CD so they can slow them down but as we lose our epigenetic information our ability to read the right genes at the right time that's beyond the expectations of the sirtuins and mTOR we need something more potent to really reset the body's clock now the body's clock we actually understand a lot more about that now we can read that clock in our blood and in our tissues and it's at the level of the genome and the changes to the genome we've been working on ways to actually reset literally reset that clock mm-hmm and that would be the way to not just live an extra five or ten years in a healthy way but potentially take a 90 hundred year old and make them feel decades younger pretty quickly Wow so what are the the big questions that you're wrestling with right now that you're trying to get answered and what would be the studies that you would like to see conducted the research you know in your perfect world that would help you make the breakthroughs that you know you're attempting to make in this well but the the hot area now as the NAD boosters move into drug development and so that's that's on its way what's coming down the line that isn't well known is called cellular reprogramming this is truly resetting that epigenome what it is it's essentially telling the cell can you go and find the information that once existed when you were young and ignore all the other information that's accumulated over time we call this epigenetic noise in my lab that's a term that we've had to coin because we've run out of vocabulary so epigenetic noise as I mentioned is caused by mostly DNA breaks and other things that occur to us but how do you say to the cell your DNA should be wrapped up in that those histone proteins this way and just to ignore all those other changes that have occurred so we think we've found a way at least what early days I don't know if you and your listeners are familiar with the pluripotent stem cell technology where you can take a skin cell and turn it into a stem cell mmm No explain that yeah so there's a famous scientist called Shinya Yamanaka and he won the Nobel Prize in 1903 2012 and what he found was that by turning on four genes in cells and they can be hair cells skin cells liver cells he can take an adult cell and make it super young again so that it now is what we call a pluripotent stem cell column IPS for short those can be made into any other cell type such as an egg or a liver cell whoa so you could literally take any any human cell pull up pull a strand of hair track to cell activate those four genes and end up with this stem cell well not only can you we all do it now it's commonplace every graduate student it typically works on this stuff so it's commonplace but the trick is how do you use that technology for human health and we're just learning how to do that now but what's crazy is so I could take your skin cell and I could make a sperm out of it I could make an egg out of it and I could make a new you that way it's crazy stuff but that's crazy but it's doable but getting back to aging what does that mean well what what we decided to do with some other colleagues who are also in this field is about four of us turn on those Yamanaka factors as we call them those reset genes not in a cell in the dish but in an animal and maybe one day a human because maybe we could use them to partially reset the age of a cell we don't want to go all the way back to beginnings we don't want to turn us into all into a stem cell that would be the end of us would be a giant to our Tomer or giant cancerous tumor but if we could just do a little bit just pulse the body so that it goes back to the it's earlier age that would be the big bang that in biology that's just straight-up out of a science fiction movie well that's what your face just lit up like a Christmas tree though like this is definitely what gets you excited well it does and it did sound like science fiction and that's why it took me a couple of years to convince my students to work on it because they thought it was crazy and it would be impossible but then there was a study that came out from the Salk Institute done San Diego from Juan Carlos Belmont his lab and he did that crazy experiment before we had a chance to do it he gets full credit what he did was he made a mouse that he could turn on these four Yamanaka genes in the animal once it was an adult and asked what happens and what happened was after two days the mice died okay that's not gonna win you a Nobel Prize that's not that's not a good start that's a bad day for the mouse especially but what he figured out was that if he switched the system off on that second day the mice were fine while they recovered but they ended up being much healthier and he did this in a what we call a pro gyroid mouse model but that just means a mouse that ages rapidly it's the same essential Mouse that you can find those young patients who age prematurely I thought that poor kids that get older in their 13 mm-hmm there's a mouse that is a model for that disease so the Belmonte lab they turn on these genes every two days out of a week and then no it's every two days and then they wait another two days and they turn them on again those mice lived 30 to 40 percent longer Wow so it's sort of like they're getting pulsed with it right so the argument if you want to criticize the work and a lot of people have is that they're just making Mouse the my sick and it's a form of hormesis but I didn't think that was true because we've been working on this reset button for ages and we thought that was probably the secret and one of the things we did was we had tried a whole bunch of genes for resetting and they didn't work but now we saw that those Yamanaka factors could be important that's what we did was we first of all we wanted to figure out why they toxic what why is it hurting that the and so we left off one of the genes that was really toxic it's called Mick and Mick is already known to be a cancer-causing gene so that wasn't didn't take a genius but when we put in three out of those four genes turns out that the mice are perfectly fine they don't get sick we've now put it into mice and they're perfectly fine but what we're seeing is evidence of regeneration and age reversal in those old mice and because you're seeing it in mice you know what it what does that mean in terms of human health like is this I mean I granted it's not a one-to-one ratio because you see a 30 to 40% increase in lifespan in a mouse doesn't mean that's gonna work in humans like what are the similarities and differences when we move you know up the food chain to more complex organisms yeah right so the it's fair to say that we've cured cancer in mice a thousand times over um it's a lot easier to do things in mice for some reason extending lifespan and mice may be much easier because they only live a few years or as we live 80 on average but these fundamental mechanisms that I'm describing today are found in everything from a yeast cell to a plant many animals mice of course and us so these aren't just some esoteric pathway these are fundamental mechanisms of living things so as my philosophy is that as long as we don't do any harm there's a very good chance - what we can do in a yeast cell a worm in a mouse will also work in a human because a yeast or mouse is 99.9 percent of the way there it's just that little bit of extra difference but if you ask a yeast cell where basically a giant mouse Wow so in your lifetime our lifetime I guess we should say we I don't know what lifetime means given the work that you're doing doesn't mean what it would normally mean I suppose but rationally or realistically or reasonably you know given your aspirations where do you think you will see all of this in you know 40 to 50 years from now like during our typical life span yeah what's a typical life span it's hard to see whether the world's going by looking backwards and right into in 1902 would we have predicted that we'd be flying jumbo jets and flying at a moon I didn't think that going to the moon we're pretty terrible at predicting we're really badger right outcomes so arthur c clarke said it's a very dangerous profession that he was into predicting the future but i'm happy to do it there's nothing no harm in trying to see what the future looks like and i have a front row seat so you know I'm partially qualified to make these guesses so what I see for the future is first of all that there are two futures one is if if no aging research is successful what does the world look like and that's a world that's still pretty good but it's not great pretty good in the sense that the trajectory is that a child born today in the US will expect to live to a hundred and four remember that this child is going to see the 22nd century what great things will be available for them who knows but even if so even if we don't do anything we're gonna have longer lifespans by the way in Japan it's 107 so this is it's not crazy to say that people will be living into their hundreds even given the exploding obesity epidemic and the increasing rates of heart disease and type 2 diabetes and all of these you know chronic lifestyle ailments that are being driven by you know our habits and our diets yeah that's a real problem and in fact by 2050 half the world will be obese can you believe right so that's actually one one of the developments that I'm working on developing drugs one of the companies that is I'm helping is working on an anti obesity drug that I'm hopeful will be of a large impact but yeah it's I got a drug for that what's that move your body and change your diet dude yeah right I don't mean to be insensitive there's there to that to the to this epidemic but I think there's a lot of people that just struggle with adopting healthy lifestyle habits correct but even with the obesity epidemic which is slowing our progress that line extrapolates to 104 now these are these are just numbers right these are extrapolations but I think if we're successful with the mTOR inhibitors rapamycin analogs with metformin if it's able to be widely distributed not yet but hopefully one day if it's safe enough and what I'm working on and other things that we could expect to live decades longer so in the future in 50 years from now the technologies could be remarkable so think of it think of this I'm pretty optimistic but the rate of change in technology still makes my head spin this reprogramming stuff we've only been getting results since May of last year and we're making advances in leaps and bounds we've now reversed the loss of eyesight in old mice and other defects and that's just the eye if this reprogramming really works and it's safe then all bets are off then we we could turn back the clock by decades yeah it's looking like now it's really early and I don't want to get everyone upset that you know I'm over speculating the caveat is that it's early but if you'd asked me three years ago what's the biggest breakthrough now I would have said caloric restriction mimetics and exercise mimetics but this true resetting of the clock is something very different it's a lot more powerful and potentially potentially dangerous but there is that glimmer that we've finally figured out why we age and how to turn it back and that resetting the clock really resets it's not just lifespan it's it's health span right it's not just living to 104 it's being vital in those later years like most people you know really don't want to be you know 98 years old and completely feeble and dependent on people around them just to go to the bathroom and get dressed right well most people myself included look at what life's like of a late 90 year old and you know I think God forbid I don't want to be that age and it's fair enough but what we have to remember is that we're going to extend the healthy period of life so that when you're in your 70s 80s you don't have to worry so much about getting cancer and heart disease and dementia which is a huge growing problem and we hope to compress the last period of life when you are sick the period of morbidity as we call it and that that's true in the animal studies that there's this what's called the compotes maker mortality curve that we draw a scientists and it's a curve that shows that for most of the time people are alive and healthy and then you get this exponential drop-off of people and that's true for worms and yeast as well and that happens really quickly but there's this tail now what we're trying to do is push that curve out as far as we can so that hopefully everybody one day gets to live to 100 or what if we choose 130 and then that period is maybe a week of being sick and then you die quickly or actually you have the choice to terminate your own life when you're done with it it's super interesting I mean we've seen over the years as science has progressed increases in lifespan you know we used to die forty then 50 and 60 but as you mentioned you know in the introduction of your book we haven't seen the ceiling changed that much you know the oldest recorded person is something like 122 and it's very unusual for anyone to live past 110 that was true way back in the day and it's still true today even though we're living later we're not busting through that glass ceiling on what's possible well exactly until now and taught but with the work that you're doing well I think that that's the point Richard you're right about that is that if you look at the history of humanity it's not a guide to the future again in the same way that in 1902 you would have said humans are not supposed to fly same thing we've got now technology that will we think changed the way humans can live and that people who once lived over a hundred if they spend their whole life with the right diet and the right genes plus the technologies that are being developed around the world who says they couldn't go way past that point how mark asked well I think anyone who says they know is lying I don't let me pin you down on a number well I'm trying not to cuz it upsets my colleagues when I put a number down but I think this guy is a limit I think what we have to remember that for every year you're alive you get another couple of months of life and that'll continue I think and probably be even better an event it gets pretty interesting when you you get an extra 11 months for every year you're alive mm-hmm because the science is advancing so rapidly right right and so we've been very good at extending lifespan by having vaccinations and washing hands and all of that stuff now the frontier that's left is to actually modify the body and give it protection from aging itself and that's where the biggest gains are going to come from in the future well everything is changing so quickly across the board with technology in science right now that it's almost incumbent upon people who are at the vanguard or the cutting edge of what they do to really also be in some respects a philosopher like how much time do you spend thinking about the long-term implications of the work that you do should it come to its fruition right like let's let's put our thought experiment hats on and envision what the world would look like if suddenly living to 200 was normal like what is that what does that mean for how we populate the planet and cohabitate in a sustainable fashion is that even possible right well there are plenty of people who claim they know what the future looks like they don't but I'm trying to at least model it timuel with economists and philosophers and bioethicists I feel it's sort of my responsibility if I'm gonna be part of changing the world I need to get the world ready for when this is coming and it's not a question of if it's a when cuz even if I step out of this studio today and I'm hit by a bus this is still gonna happen okay so how fast it happens it's hard to know but I I think in the next few years there will be one drug that gets on the market that to impact aging or at least aspects of it and it'll just grow there'll be a lot more so in the future they will you know sorry to interrupt but like regardless of whether we philosophize about it and how much time and energy we invest in trying to think about whether this is a good idea or not it is happening irrespective right and that's why it's the way we function well that's why you're right that that a good scientist should be a philosopher should be a humanist as well and many of us are because we've seen what's coming and vulture is a good example Volta longer okay so what do I do so I've been going around talking with politicians and with economists with policy makers with bioethicists trying to first of all wake the world up because most of the world is still asleep that this is coming but once people get woken up and I find finally over the last few years there is increasing awareness that this is going to happen then the question is what are we going to do with the world what is it what does it look like and if it's gonna go to hell excuse my language can we prevent that and I really do see I set a fork in the road that if we don't do anything now this will happen and if we do something we'll live in a much better world and I'm trying to push the world push the needle so we hand up head off into that that brave great new world and some of the things that we have to be very careful with first of all this population growth there's the environment there's what people do if they're taking Social Security does that wreck the economy to tear their lives become meaningless of a just a burden on society crazy stuff like what happens when you have politicians that have been around for 200 years and they're still making policy people on the Supreme Court a lot of things yeah yeah and and women what about them so that can can we extend their period of fertility so that a they can have a the career they always wanted to and be will they be around to take care of their great grandkids and see what happens to them I mean right now we live in a world where close to half of all women take time off during the critical period of their careers and could that change and not only that if you have kids when you're all especially men who are capable of doing that there's this response that how can you have kids when you're 40 or 50 you won't even be alive when they're in high school what that should change as well we can stretch our lifespan and help span in a way that allows us to have much more say in what we do early in life stay younger for longer mentally and career-wise take longer to find what we'd love to do and even when we're done with a career we'll be able in this new world to have second third careers have a second chance third chance at the career people always wanted mm-hmm not to be contrarian but at the same time like I'm just envisioning myself like okay I'm gonna live to be 200 and be around for a long time maybe in my 40s I have a couple kids take a break you know something happens then 20 years later I decided like I want to have kids again they're all gonna live to be 300 years old because the science will improve and we begin populating the planet with people who are gonna be around a lot longer who may be having more children that they than they would or do otherwise yes they're productive longer they're there they're contributing to society for a much longer period of time but I have a hard time seeing my way around just what I think is the biggest issue initially which is population control like how are we going to you know keep the planet from going past the ten billion mark into the you know 15 billion mark like how are you game tearing around that right well who says 15 billion is a problem that that's a debate as well well there's all these other problems that we would have to solve in order to make the planet habitable for that many people right and and I believe that they are solvable now I'm not hoping for overpopulation by any means and in fact if you if you do the numbers the rate of population growth isn't that great if people live longer surprisingly low and as the world gets wealthier particularly developing nations they will have fewer kids that's proven out let's look at the world if we don't do anything about longevity and we continue to treat one disease at a time we are already heading for a healthcare crisis Social Security's going bankrupt we've got healthcare occupying 20% and increasing GDP of this nation around the world we're being basically dragged down economically by health care costs the proportion of people getting older is growing dramatically right now for the first time just this year we've got more people over 65 in under 5 so there's there's a gray tsunami coming that's right here really that's that we have to deal with so what's the best way to deal with that well you you can't just go around hoping that older people will die off in fact that's a huge waste of resources there's oh but mostly productive we have wise people so that the solution I think is to make them and keep them productive members of society my father who's gone back and started a second career and helps raise the kids they're not a big burden on society if they're productive and they're living alone and or they're not in not needing any help at home and that's a huge cost saving that's in that it's or not they're not a drain on society they're not requiring all these health care costs and governmental assistance and they're actually being productive and yeah and so Dana Goodman who is at the RAND Corporation he calculated that of all of the medical treatments that are being developed from angiogenesis inhibitor services for heart disease and pacemakers cancer treatments diabetes the one that gives you by far the biggest bang for the economy and for your life is an anti-aging as he called it anti-aging treatment and to give you an idea of the difference to a pacemaker advanced will extend a human life at the cost of I think it was a million bucks to the US economy to do it for a calorie restriction mimetic anti-aging molecule it was a I think $7,000 first a million so it this is a cheap way to prevent the this loss of the economic activity that's money remember if it's fifty trillion dollars in the long run that it's calculated to be saved by doing this that is money that can then be used for helping the environment helping save species help figuring out things like energy let me give a really good example of why I'm really optimistic about the future we humans can solve anything if we just put our minds to it and that that's been proven out I mean these days of got a supercomputer in my pocket for goodness sakes in Australia there was a coal-fired power plant down in South Australia and there was a big jetty a wharf where they would just bring in coal day-in day-out burning coal global warming contributor turns out it became too expensive to run that coal-fired power plant so they shut it down putting thousands of people out of work in this little community so a brilliant bunch of bench capitalists said we've got human capital we've got this wharf we've got a lot of sunshine it's on the barren South Australian coast what are we going to do with that and they figured out let's use the sun's energy to pump millions of gallons of water out of the ocean purify it put it in greenhouses and these days there's 30,000 tons of tomatoes being shipped out from that Wharf in South Australia and those people that lost their jobs most of them got a job at the farm I love that story I wish we could replicate that you know across the board in so many industries that are quickly becoming antiquated and environmentally you know hazardous and there's so many problems that that I'm concerned about that I feel like despite our industrious nature and our best intentions we we just fumble over ourselves and are unable to to solve and and that tempers the optimism that I have that I share with you when I see that when I see problems that are right in front of us then that we need to solve and we're seeing incapable of doing it I don't know whether because there's no political will or there that the incentives are not properly aligned to make it happen I agree with you and when I was I was young I was pretty negative I didn't even think humans belonged on the planet we should all just kill ourselves we didn't deserve to be Wow that's the dark yeah but I've evolved as a good-old right I've become much more optimistic that I've seen what's possible when you bring armies of smart dedicated people together and that's what I see my job it's one thing I've found that I'm okay at is finding a goal and then bringing people together to solve what seems to be impossible and you're surrounded by tons of super smart people what about the psychological implications on a young person who's presented with the this new reality of living to be 200 or 300 years old you know talk about a change in the incentive landscape like that person suddenly is no longer in a hurry to figure things out like how does that impact an individual in terms of how they make decisions about how they're gonna make their way in the world when suddenly time really isn't it isn't the ticking clock right that your grandmother spoke about yeah wouldn't that be great I think that it's a shame or does it just create a bunch of lazy people oh well I think it can be a drain on society people will be people right though those of us who get up every day with a mission will continue to do that no matter what age they are and probably vice versa but it does it does give you a different perspective so the way we live our lives now we expect to live to 80 and if we're healthy beyond that but what that means is that we're now teens we have to grow up we're now 20s we have to find a profession in our 30s we have to get good at that in our 40s we make the most of it in our 50s we're looking at what what is our legacy wouldn't be great if we could be 60 or 70 and say I finally figured it out and you know what is my legacy gonna be and just start again or use all that wisdom to do something brand new and we are entering a world like that when we were kids being sixty was old 70 was I'll forget it and a lot of people that I knew in their 70s wouldn't even know how to type on a computer and I find that people now that are in their 70s and 80s they're playing tennis and typing yeah yeah Twitter so we're living in a different world and just like today you know 80 is that is is 50 essentially in the future ninety hundred year olds will still be just as active as we are in our 50s yeah when you your focus is in the hard science geneticist but I can't help when we're having a discussion about longevity and aging I can't help but think about the blue zones and the characteristics of these you know little pockets across planet Earth where we're finding populations of people that tend to live longer and be happier than others and and what are their shared characteristics and of course it's certain diet protocols it's you know having an active lifestyle that isn't running on the treadmill but being kind of consistently engaged in some kind of low-grade movement throughout the day but on top of that there's also this aspect of faith most of these communities have some kind of faith that congeals them that creates you know a community sensibility that that to which they collectively adhere and also this sense of purpose like I think it's the Okinawans who call it the Ikki guy right that they're driven by something that exceeds their personal ego like that that is fueling their life with with meaning really that gives them a contentedness that makes them a healthier person and able to live longer yeah 100% if you don't have a mission in life go get one it'll it'll keep you happier and probably longer leaped as well haha like you can take all the resveratrol you want and you know we could talk about the genetics but if you're aimless and you don't have purpose and you're you know mentally you know not dialed in and you're not taking care of yourself and you're not eating well you're missing the big picture well this is the problem with retirement I mean it's all it's all fine to go on cruises and enjoy some relaxation but once you've lost your purpose that's when things go downhill and I saw that with my father actually my father retired at a typical age of was a 66 87 and spent was about 10 years just flailing around you know you can only I think go on so many cruises before you get sick of it it wasn't until he started his new career which is working at the University on an ethics panel for experiments that he hooked up and he was excited about life and I've never seen him happier isn't that crazy that someone who's essentially 80 turning 80 has never been happier or more vigorous that's really I think inspiring and shows me what the world could be like for millions of people hmm yeah my my wife's father was an engineer in Alaska he passed away a couple years ago but he worked well into his late 80s on gigantic construction projects in Anchorage because the community there is largely Native American and they have a reverence and respect for their elders that is kind of lacking in most of you know the rest of our culture and they would continue to employ him he kept saying like I can't even see anymore they're like what they respected his his experience and it was just like the right thing to do and he did contribute you know in a very material way to advancement of these projects so he worked essentially all the way to the end and it just defies that whole paradigm of people you know this the great generation working towards their retirement and 401k so they could live out the rest of their lives in leisure playing golf and hanging out at the club I'll need to discover that that's the thing that makes you depressed well it really is and and so society would be so much better if if people stayed healthy but also we're able to contribute it's getting up in the morning and knowing that you've got something to do right it's important and on the retirement age no I think that if you've been busting roads your whole life you really deserve to have a second chance so I think that as nations become wealthier and we're already finding that people are talking about a we call a living wage when people take time off work I would suggest that the best thing we could do is people get healthier for longer and just sitting around being healthy that they actually have a choice to take some paid time off to start a new career so let's say someone who's been busting roads oh no that's just a catch-all term for someone who didn't like their career gets a few years off paid by the government to do what they always wanted to do and it can be anything can be building model airplanes or helping out at nursing homes but that living wage would come back in in huge dividends because then you'd have people like my father who are helping society it doesn't even have to be paid work by the way but I think just getting people with the wisdom and knowledge that they've accumulated over a lifetime instead of just throwing that away into the ground or as a crematorium let's use that human capital it's worth trillions of dollars and we just throw it or throw it away hmm yeah being able to leverage the collective wisdom of centenarians who are mentally fit enough to pass down their wisdom and experience to a younger generation and at the same time changing our perception of the elderly you know right now we warehouse them we dismiss them we want to pretend they don't exist we want them to go away we don't want to hear what they have to say I mean I think there's some cultural shifts that would have to take place as well well they would I I mean who isn't who wasn't a 20 year old who's guiltiest you don't want to hang around the old five I'm gonna change that is not going to change but you know I think as you get older you realize that they're they're very special people anyone who's managed to survive for 80-plus years and what they've seen especially people who had to live through World War two then one of the worst times in human history what they can tell you about the meaning of life and also what I've learned in life is it's important to learn from mistakes not just success and everyone's had mistakes but if you can see what the mistakes others have had in their lives before you make those same mistakes that's really the way to avoid the pitfalls in life and I've really benefited from having some mentors in my life I would love to these days sit down with people who have these stories to tell about what have they learned in their life that they could pass on to future generations right well in terms of passing on wisdom down the line I think we should round this out with some practical wisdom and advice for people that are listening in terms of things that they can do in their daily lives to improve their longevity and combat aging to increase their health span what are some of the top things well here's what I do that's how that's how I convey advice so every day I wake up having had a decent night's sleep preferably and I'll go have a yogurt that I make myself for the microbiome trying to keep my microbiome in check I take a little bit of resveratrol sprinkled in that yogurt is there a particular brand or do you have some special Harvard lab version that no one else can get except for me cuz you're gonna get it to me right uh well we'll talk I fortunately have pharmaceutical grade rose virtual harassment so it's okay and same with any men and is that that's not commercially available can people get that from me well for you you don't count because you're working in it but for somebody who's listening like they can't go to their doctor and get this broad drive and they purchase right well there's a lot of things sold online which I apologize I can't endorse or talk about it's just I try to stay above that fray but there are people selling things online that and I'm good I'm gonna use social media to be able to talk more about it so stay tuned okay I'll release what I can but I'm also looked out looked over by a very large institution called Harvard University writing careful what I say and what I do but I also want to be able to say with authority the science so anyway my apologies for not being able to say go buy this product I just am NOT able to say that but I can point you in the right direction I think you should look for if you're going to take a supplement make sure it's from a reputable source and there are some reputable companies some other or not yeah sometimes it's hard to know there's really much out there and there's a lot of quackery yeah so my my dream riches to have an independent group who does these studies and leaves me out of it but maybe I can enable that group to test things and report on it and that would be the ideal but I got into trouble when I used to talk about supplements I once said on NBC or a TV show that some of the supplements I've tested don't have the product in it and that got some people very upset and I got dragged into a fight between two companies and it was a lawsuit and I lost her a year's salary on unload on legal costs so that you know is a good lesson don't talk about supplements if you can help it you know that said look for quality brands look for purity don't take things that have a lot of mixed things in it you just don't know what else you're getting in there look for clinical trials that have been tested on some products so some products that raise nad have been published in clinical studies and so you can go to PubMed it's mm-hmm Google the words PU bmed you can find some scientific papers and look first so to ends look for nad look for either nmn or it's similar molecule it's cousin called NR just and and actually wondering what's in our it stands for nicotinamide ribose I'd so that's as best I can do to help there I try to do some exercise at least once a week on the weekends my son and I go for to the gym for two to three hours there just once a week well we try to do more but I'm traveling a lot so hopefully twice a week at minimum with we have a gym at home actually I built a gym adjacent to my bedroom which I can see through the windows and for a while there I figured just looking at the gym is probably helping I was hoping at least okay yeah mentally you know if I just look at the treadmill it's probably good but now I try to use it more and more especially because I've been writing this book and I've spent hundreds if not a thousand or more hours sitting down which is really bad try to make up for all of that so we do that we do high-intensity running on treadmills and we also do weight training with with a trainer every for an hour and actually amp my trainer recently looked at my body and he said I used to work out when you were young and I said yeah I did how do you know it he goes cuz you're all messed up my arms are turned inward my palms aren't straight I slouched to one side and so he's fixing that part of my body but so I'm trying to get back into shape is there research on the differences between high intensity training and aerobic training in terms of longevity not in lunge evety as much there have been some human studies that have looked at biomarkers and other things like that and it and also the relationship to to frailty and what as far as I can tell from leading up reading a very complex body of literature is that you want to do some not high impact but high-intensity aerobics get your heart rate up pretty high until you're feeling some hypoxia you gasping for breath and that hypoxic response is a hormetic response it will stimulate your body to fight back so get get your heart rate up they say as little as five minutes is sufficient I don't know I go a little bit further I don't see any harm in doing that so you know 10 15 minutes of panting but then I slow down and then I do a bit of jogging as well but it's that really what you just want to do a bit of jogging a bit of sprinting bit of jogging bit of sprinting but it doesn't seem to have to last for that long to be good for you just to get that or that stimulus-response yeah because your body has an epigenetic memory of those exercises and so it lasts for days unknown what about training 25 to 30 hours a week for ultra distance triathlons and marathons yeah it's about digging my early grave I don't think so I've seen data on on bicyclists has it not the same thing but bicyclists who I think they were riding over 80 miles a week their chance of getting heart disease was reduced by 40% in old age and 40 percents a massive number and so I think that you know if you're not wearing body parts out certainly your organs are gonna be younger for longer yeah although there aren't there's some there's some research out there there's some research out there that says long term like super you know a lot of aerobic exercise ultra marathoners marathoners have scarring in their heart tissue and there's some cardiac implications that don't look so great for that I'm always getting tweets from people all the time telling me that I'm harming myself oh well I think you're gonna live longer than someone who sits on the couch and eats potato chips all the time so I can't speak for the fibrosis in the heart expel them to say we're also working on that well I have a sin oolitic company with some real experts in the field like I Manuel Serrano in Spain who cloned the senescence gene p16 so we're trying to figure out how to fix problems like that that it came late overtime right okay so exercise what about what's your specific for a fasting protocol look like then I don't have one I do try to eat smaller meals I try to not overeat and I try to skip meals which is pretty easy because I'm not hungry when I wake up other than that little yogurt which is just for virtual solubility and then I'm so busy I usually skip lunch so I'm I'm practically eating one maybe two meals a day by default I am never able to literally go a whole day without eating for some reason it's just too hard I'd like to I think that would be a great thing I know Peter Atia does it really well and others but I'm unable to I think I've got to feel my brain without my brain I've got no job so that's all I be able to think straight right I think better when I haven't eaten you know you get the brain fog after the lunch and the lull and the energy sometimes it's better to eat without food terms of focus for me personally I agree with that hundred percent but then you get to a point after diminishing 24 hours yeah it starts to go down so you're not super hardcore about these kinds of practices no I probably should be better I doubt it yeah but as I've said I'm not I'm not so worried about my longevity I mean I'm hoping not to die in the next few years because I've got some work to do uh-huh I try to be a role model for others but I'm not obsessive about it I do have some bad genes that I inherited so I'm trying to live at least 80 to 90 years I'd like to live longer I'd love to be able to continue working and doing good I'd like to see where the world goes with all of this research I'd like to figure out what we have in our pockets besides computers when you use from now but you know to your point I do what I can within reason most of my mental energy and dedication is devoted to this cause which is finding cures for diseases improving people's lives getting the word out that this is coming and this is important for the world to know about one last question sleep if so much of what we've talked about is trying to get the body to get into its reparative State isn't sleep the ultimate example of that is this not something that we should be really trying to enhance and focus on for concern about longevity yeah well the first of all that the longevity genes that I work on are central to the cicada in rhythm which is the sleep/wake cycle and if you're out of whack and you don't get enough sleep that we think has negative effects on the sirtuins and nad levels nad levels will precisely cycle with the day just before you wake up or before you have breakfast your nad levels will start to spike and get you ready for the meal so if you start to miss sleep and you get your if you have a lot of jet lag like I do it's not good we know that mice when you mutate their body clock they get signs of premature aging and in fact if you prevent a rat from sleeping it'll pretty quickly develop diabetes so it's really important to maintain a a good cycle and reset your body clock if you're traveling and then the other problem is that without a proper sleep you're not clearing out or the the toxins that accumulate in your brain and we just recently a scientific world has realized that as you're sleeping and dreaming one of the things that's happening is that those canals in your brain are getting rid of what's built up during the day and if you wake up early and you haven't had enough sleep your brain is still clogged with that stuff and so you can't think well during the day which is lethal to someone like me who's supposed to be a peak performance mentally um so let me tell you about what I do because I missed out on sleep for more than a couple of decades I'm an insomniac actually oh wow and with kids it didn't help that at all so what I managed to do was to calm myself down at night I'd do a little bit of meditation avoid the screens the blue light I wear those light blocking glasses yeah if I'm traveling I'll take a little bit of a sleeping pill which I need to just calm down but I don't eat the whole thing I just nibble on the pill and that's enough to calm me down so I finally get to sleep because my brain is so active it would keep going all night and then waking up in the morning they find that that combination of the resveratrol and anime and a little bit of coffee really kick starts the day and I'm ready to go um and by the way please don't criticize me colleagues for saying this because it's it's an N of one as we call it but I find that jet lag is ameliorated its lot less when I travel and I use the nmn to reset that body clock which you know we now know at least in mice that cycle of nad through the day is probably what's driving jet lag as well if and also it helps you get over the jello now well I find it does for me and I travel a lot enough I experiment a lot on myself with this these things and that's one thing that I am pretty sure is true is that the anime helps with that gentleman when's the book coming out well it's set what's it do you have a title for it yeah it's called lifespan a lifespan okay cool yeah so we're we're I'm just finishing it up it's an illustrated book it's got some beautiful drawings illustrations from one of the best illustrators in the country and so some of these concepts like the epigenome and compact discs they're beautiful when they're drawn out on the page and so Katy Delphia has been working for a year on this book as well and I had a co-author Matt LaPlante who has written a book about the epigenome so the three of us have created what I think is a unique book unique it's science-based but it covers everything from the beginnings of life on the planet to human history and life in London in the 1830s what we can learn what we I give the readers a front row seat on what the cutting edge of technology is today what's just around the corner because I can see it already and what does life look like in the future for our our families for our family members including our four-legged ones and project into the far future of what the future is gonna be like if we don't succeed and if we do it's gonna be interesting either way it is but we got to stick around to see it yeah yeah yeah well I really look forward to the book please send it to me when it's ready and hopefully I can entice you to come back and talk to me a little bit more when the book comes out sounds good rich thanks for having you thank you so much for the work that you're doing it's inspiring it's fascinating we really are creating you know a world beyond anything we could have imagined as young people and you know it's a privilege and an honor for me to speak to somebody who's really at the cutting edge of all of that so thank you for your time and best of luck with all of this man doing amazing work oh thanks I appreciate you all so if people want to connect with you or learn more about your world and what you do what's the best place for them to go so I'm active on Twitter and I talk about some of the research in my lab we've got the immortal jellyfish gonna just tweet out at new transgenic trained jellyfish we made last week so that that'll be the way so that my twitter handle is David a Sinclair and so we're gonna launch a book website soon but Allah I'll let everyone know when that's ready cool good talking to you thanks Rachel feel good I always build it did you good I want to always feel good we'll talk more all right thanks man peace [Music] mind officially blown this conversation which incidentally transpired a couple of months ago really deeply and profoundly impacted how I think about my personal longevity my aging it shaped some new daily habits that I've been ascribing to including daily intake of resveratrol which we talked about during the podcast for those interested in that product I'll put a link up into the show notes and I really hope you guys enjoyed it please do me a favor let David know what you thought about today's conversation you can find him on Twitter at David a Sinclair and don't forget to pre-order his new book lifespan the revolutionary science of why we age and why we don't have to which hits bookstores on September 10th if you'd like to support the work we do here on the podcast just tell your friends about the show share your favorite episode on social media you can subscribe to the show that's probably the most important of all of these things if you hit that subscribe button on Apple podcasts on Spotify on YouTube super helpful leave a review on Apple podcasts and you can support us on patreon at Rich roll com forward slash donate I want to thank everybody helped put on the show today Jason camiolo for audio engineering production shownotes interstitial music Blake Curtis and Margo Lubin who traditionally video and edit the video version of the podcast although this one was audio only Jessica Miranda for her beautiful graphics and DK David Cohn hashtag DK goals for advertiser relationships theme music as always by analemma thank you for the love you guys I will see you back here in a couple days with another special edition hotly-anticipated edition of Coach's Corner with Chris health my coach Chris health until then take care of yourselves embrace life it's not necessarily the length of time we spend here on the planet but the quality of that time so be mindful about it appreciate it be grateful and give back peace plants [Music]

Channel: Rich Roll

Views: 335,384

Rating: 4.8218536 out of 5

Keywords: aging, Alzheimer’s, apoptosis, athlete, cancer, david sinclair, death, diet, disease, doctor, fasting, fat, fitness, harvard, health, heart disease, inspiration, intermittent fasting, life, longevity, meditation, medical, medicine, mindfullness, MNM, motivation, nutrition, PhD, plantpower, plant-based, podcast, protein, rich roll, science, self-help, self-improvement, vegan, weight loss, wellness, hormesis

Id: bF5yl9OGKzw

Length: 140min 14sec (8414 seconds)

Published: Tue Apr 23 2019