David Sinclair

00:00here we go 5 4 3 2 1 David Joe how are you sir great thanks thanks for being here man I appreciate it thanks having you know really looking forward to talking to you very much so this is a fascinating subject for me anti-aging the idea that you'll be able to stop aging or even possibly pull it back or if they're very least slowed down what do you think I think that's all on the table we've been doing this for years in the lab now we could just gotta figure out how to do it in people when I talked to someone like you as an actual research scientist of this stuff I always want to know what are you doing to yourself ah how long have you got like what do you do a daily base I do first of all are you 100 years old get in there how old yeah 20 50 so you turn 50 mm-hmm I wouldn't have thought you were 50 I would have figured you're about 41 42 well that's kind of you well

00:57my brother's the negative control and he's he's delivered well I can't say that but people say that he doesn't look as young as me and he's about three and a half years younger oh so what are you doing personally well you know most of the time I'm in a lab and trying to run a bunch of companies to make these drugs a reality but daily I try to keep a healthy weight I do intermittent fasting which is pretty easy because I'm so busy I forget to eat how many hours do you give yourself every night uh well I suffer from late night snacking but I try to skip breakfast and even skip lunch if I'm busy so I'm a night eater but that seemed to be good because a study came out about a couple of weeks ago at least in mice that it's not what you eat it's when you eat that's most important for longevity really and when when being when like what's the best it doesn't

01:48actually matter if you eat a lot in the morning or a lot at night I like nighttime eating but you need a period during the day at least if you're a mouse probably if you're a human where you're hungry and that puts your body in a defensive mode and these are the things that we've been studying my lab for the last 20 years what are the processes that diet and exercise do for us they keep us healthy and why does calorie restriction and intermittent fasting make animals live so much longer and we think we've figured out a large part of how that works and now we're mimicking that with molecules is the is the idea that you can mimic it with molecules and it'll be as effective as intermittent fasting I think the molecules will be better and not only that when we add them onto a healthy diet and exercise any animals they do even better it's like a supercharged Mouse now when you add them

02:38on to the mice do you also add them on with intermittent fasting and is there an additional benefit we do we do one of the first molecules that inference molecules that we are known for is resveratrol from red wine that molecule discovered it in like 30 so at least linked it aging what we showed was that if you give it to a fat Mouse they're as healthy as a thin Mouse they live just as long they didn't get heart disease and all of the other bad stuff then what we did was interesting we gave it to the mice either everyday in their food or let them skip a meal every day so that they were fed every other day and that combination of resveratrol plus every other day feeding we had the longest lifespan we'd ever seen and it was salt was additive same with exercise if we give our latest molecule called atom an to a mouse and we exercise it it'll run even further than it could with either

03:30of those alone so it's not an excuse to sit around and just eat chips and watch TV it old man's healthy lifestyle gets you further than what you could get naturally so in any are you seeing a benefit in addition so is the idea to compound all those things together exactly right so you asked about myself so I I do I eat healthy I try to skip meals I also take supplements and in fact most of my colleagues are in the field of aging or anti aging as people call it so I take animun every morning what is nm and good question so let me take a quick step ashore so about 20 years ago Lenny gurantee and a team of us at MIT discovered a set of genes that controls Aging in yeast cells just brewers yeast what you find in beer and bread and those jeans are called sirtuins and there are seven of them in our bodies five in yeast and what they do is they protect all organisms on the planet

04:27plants bacteria humans from deterioration and disease they're like the Pentagon they sense when we're hungry since when we're exercising and they send out the troops to defend us so when you when you put more of these genes into a yeast cell or a mouse they'll live longer between five to 20 percent longer and so we think that these genes are responsible for the effects of dieting and exercise which is great which what that means is we can now mimic that with molecules so an amine is one of those molecules so is resveratrol you can think of virtual as the accelerator pedal for the sirtuin genes and the animators that is a fuel and without fuel reserve Lorent work so any man is the gas in the car I've heard of resveratrol but is nmn a new molecule this is commercially available some people have started selling it on the internet it's related to n R which is sold by a bunch of

05:20companies and our yeah nicotine my driver-side is a supplement that raises the levels of a molecule called nad shopping list so they get a pen so why are you writing that down to that so there's our two ins okay get this so sirtuins need nad mmm-hmm to work without them they don't work in fact if you don't have nad in your body you'd be dead in about 30 seconds it's a really important molecule but as we get older we lose any T so by the time you're 50 like I almost am you have about the half the levels of once or you had when you're 20 so that's not good and these sirtuins they don't protect the body without high levels of nad so what n MN does and this other molecule called NR which both you can get on the internet they boost the body's levels of nad back up to youthful levels again and if we give them to mice these molecules t2 mice or even two worms or yeast they

06:17live longer and they're super healthy now what level how many milligrams are you taking of these things so yeah n MN is is something I get from for myself I'd I'm not selling anything so I take a gram of any men in the morning based on clinical trials has been shown that that will raise any deed with or without food I take a little bit of yogurt that I make my cell at home just to me you have been doing this for a while and I only start doing stuff when I see it working animals first so take take the yogurt mix in some resveratrol resveratrol is great but it's really insoluble it's like brick dust so in the yogurt it will dissolve take another half a gram of resurrect roll and how much half a gram yeah it's a it's a powder I have a few kilos left over from clinical trials in my basement so yeah that that's gonna last me a few decades and then I also take at night some metformin which is

07:13probably the most radical thing that I take which is a prescribed level drug for diabetes net Foreman met met M MIT and prescribed Abul drug so you don't have diabetes I do not but you take it for for preventing cancer heart disease Alzheimer's and aging met spell Emmy t fo RM i N and so out of studies of 10,000 people and more it's been shown that people who take med form in even if they have diabetes are protected against other diseases of aging even frailty and some most scientists if you ask them in my field will say yeah metformin is likely to extend your lifespan it's just that the FDA doesn't let you have it for aging because aging isn't a disease yet so do you have to get diabetes to get it or do you have to get a sneaky doctor well I wouldn't call a sneaky doctor but the doctor typically has to be convinced because they don't keep up with the literature and it's

08:12it's off-label okay alright and how much do you take it out I take a gram of that as well which is about a low dose as some diabetics take 2 grams so it's not crazy amounts as they're in side effects well the good news is that it's extremely rare that you get sick from any of these molecules in millions of patients around the world nobody's getting sick the worst you'll have as far as I can tell is a stomach upset and I get that which is actually helpful if I'm hungrier I lose my appetite but I think the downside is extremely low and that the upside is you know anything's better than what's coming and what is the mechanism that foreman is operating okay so that so this is the great thing is that over the last 20 years we have figured out we scientists have figured out that there are universal regulators of aging from yeast to worms to mice and in humans and

09:05there are three main pathways that we figured out respond to what we eat and how we exercise and one of them is called ampk and this is a target metformin and so I'm active when I take med form and I'm activating my AMPK which will send out the troops the sirtuins I've mentioned that's the second of the pathways and so I take animun and research all for that and then the third one is called mTOR which is a pathway in the body that responds to how many amino acids how much meat you're eating and it will also protect the body if you tweak it just the right way and there's only besides eating low amounts of protein the only way to affect their pathways with a drug called rapamycin which is which is a little dangerous to try and is is used for immunosuppressant so it's not something that I would recommend and I don't take it Wow so this is your daily routine along with what what kind

10:07of like diet do you follow well I I try to not eat too much it's pretty easy to overeat so I try to skip one or two meals a day I avoid sugars and carbs I try to run once a week I do workouts on the weekend like you I love saunas I like to put my body in some temperature stress so I go heat and then I jump in a cold bath mm-hmm back and forth that that works well for yeast we can do that in lab and they live 30% longer so there's all that you have generally generally I eat normally do you ever try going from sauna to cryotherapy no I haven't tried actual cryotherapy just to oh you haven't done it at all no you want to do it today harvey got one yeah yeah we'll take you take you down the street there's a great one because it's there's different kinds and some of them are from the neck down where they're using liquid nitrogen the other ones they actually freeze the air

11:03so when they're they're using the nitrogen to freeze the air and they're pumping in air that's 240 degrees below zero and you're you know you're gonna do about two minutes I do three because I do it all the time but it's awesome I do three and then I take ten minutes off and I go back in for another three yeah makes sense and what you're doing to your body when you do that we think is to activate these longevity pathways like this or two ends yeah and and that's really the trick is to activate your body's defenses against aging I mean the old theories about aging you've got to throw them out most people at parties will tell you oh antioxidants free radicals DNA damage or mutations that is all for the most part in correct that antioxidants cause DNA damage no that's true that it repairs DNA damage well antioxidants have been a rather big failure in the aging field but

11:54resveratrol is an antioxidant correct it's a mild antioxidant but it doesn't work by being in Antioch so what does it work what is the pathway it steps on the accelerator pedal of these sirtuin enzyme okay and so it's directly controlling the body's defenses against aging so as we discussed it or as people discussed it as an antioxidant it was just a mild form of antibiotics antioxidant but it didn't so much more right and we know this because if you create a yeast cell or a worm or a mouse and then you knock out the gene for the sirtuin now reversal doesn't help the animal anymore that's interesting because when people talk about wine that's the one thing they say the resveratrol is and antioxidants really good for you yeah this is one of those open myths that never goes away and still fuels a billion dollar industry but what we're finding is that the

12:41molecules in plants like resveratrol first of all that we think they're produced by plants because the plants are benefiting from the stress we call it hormesis a little bit of stress is good for you what doesn't kill you makes you stronger kind of thing and hormesis was discovered oh about 60 70 years ago when people were spraying herbicides on plants and a little bit of herbicide actually made them stronger and we think that these molecules and plants are similar they make the plant stronger during times of stress so if you stress a grape that's four winemaking you'll get great wine but you also get a lot of resveratrol and so when we ingest that resveratrol from the plants we get the same health benefits because the plants are activating their sirtuin pathways and we have the sirtuins and they activate us as well ah interesting interesting so low carb

13:30low sugar any specific type of protein do you limit your amount of protein yeah I mean I enjoy eating mammals just as much as anybody but I try to avoid them for the main or two main reasons one is that there's this TMAO a molecule that seems to cause heart disease TMAO yeah yeah and how is it linked heart disease is these epidemiology studies I forget but I do recall that the study was able to give the TMAO to animals and they developed heart disease so it's somehow causing it I forget exactly how it might be damaging the genome that's my recollection with omnivores or predators I think as red meat is the culprit right so are they giving this to rats are they giving this to there was a male study again so I mean mice might be different from humans of course yeah but the other problem with with meat in general from from animals is that there's a lot of mean always in there

14:30and it's easy to eat a lot of meat and so if you have high levels of amino acids it will activate this mTOR pathway one of those three longevity pathways and you don't want that you don't want that you don't want that because mTOR has evolved to sense times of adversity and stress and hunger so why do people see a performance benefit when they consume branched chain amino acids really good question so in the short run just like taking testosterone it will give you performance benefits but we think in the long run it will actually come back to bite you so how will blend branched chain amino acids come back to bite you so branch chain amino acids will activate this mTOR pathway and when we do that in animals we actually we reduce their lifespan so it's the opposite you want to keep those levels low that's interesting that seems I mean for a dummy like me it seems

15:28counterintuitive because what's making you perform better you would see you would think especially something like amino-acids a natural part of the human body you would think that would be beneficial you're adding to your body something that it needs yeah you would but but what you should consider is that it's a trade-off there's a theory that's probably correct it's the sum Tom Kirkwood's to your theory called the disposable soma and our bodies want to do one of two things either want to grow really fast and reproduce fast build up a lot of muscle cells divide that's great in the short run you know you'd be fertile you can run but actually that is at the expense of hunkering down and building a long lasting body and then it's a trade-off over time and so animals that grow fast and reproduce fast like a mouse will only have a short lifespan or as a whale

16:20that grows slowly and reproduces slowly will live a long time interesting so the idea is you're you're limiting your calories you're limiting your carbohydrates you're limiting your protein you're limiting your amino acids but you're ramping up on all these beneficial molecules right these these pathways that have evolved since the beginning of life to make us live longer during adversity so we can thrive when times come back that's good do you take into consideration quality of life versus length of life like is there a like a sweet spot yeah that well it's hard to ask the mice how they feel but they we do test them and we do frailty studies and we can see that they've got better memory and they can run further on a treadmill they're stronger those kind of things they see better and you know we think that that probably means they're happier as well and when you're

17:16taking in protein so if you're not eating mammals are you eating a lot of fish yeah fish is fine white meat I indulge I like chicken that kind of chickens fine not too much of it but I'm trying to eat as many vegetables especially the colored ones for the reason that I said which is well a few reasons one is that you don't ingest as much protein as you otherwise would you get all those vitamins because I get those molecules from the plants that we think make you healthy so reservatrol just one of a bunch of polyphenols that plants make when they're stressed and when plants are stressed they go colored so that the purples and the reds and blues yeah those are molecules that are generally healthy and I think I'm one of the few scientists um who thinks this but I think that we've evolved as animals to sense the plant world and when our food supply is stressed out then our bodies

18:08sense that by when we ingest them we get these molecules like resort all and we've evolved a sense that and we get the benefits of longevity as a side effect so mm-hmm this is really fascinating to me because the idea that you're trying to balance out that this site the concept of a mouse growing very quickly but dying quickly as well versus something that can extend and live longer and and be more vital or have more vitality for a longer period of time well so here's the great thing is that now that we've we believe we've figured out why not just why but how this all works what are the genes and pathways in the body that control this we can have our cake and eat it too we can at least in a mouse and probably in a human in a few years time and maybe even with these supplements we'll see we can trick the body into being hungry and being in adversity even if you're eating a lot or

19:09you're not exercising and so we can return slowly but of it eventually turning a mouse into more like a human so that you even though you can grow and reproduce quickly you still turn on these protective pathways and live a long time the best example is the the nematode worm art C elegans that's been studied a lot for longevity and the mutations that make those worms live sometimes - and up to ten times longer are activating genes that are normally only turned on when they hunker down and turn into a little dour Tower or a stage which means that they're they're not really reproducing they're just hibernating so you can have a hibernation of benefits but still live a normal healthy life and this is from manipulating genes right so this all comes from genetics so I'm a geneticist at Harvard and the way the breakthrough came so go back in the 1980s it was antioxidants

20:04mutations because people really didn't have a handle on what was going on and the idea that you could slow down aging with one gene or one drug was ludicrous because it's so complicated but now we know from genetic studies is that you can find mutations hundreds of them actually in organisms that lengthen lifespan so it's not as complicated as we thought what about mile statin inhibitors and the studies that they've done with my so they turned them on and off and they've grown those super mice yeah Hulk mice well being a Hulk doesn't mean you'll live longer right didn't they live longer though I don't know did that I believe they did I think that was one of the weird side effects well if you allow me to speculate as to why that might have happened is so being bulky is good let's finally I'm correct first yeah well one of the things if both he is good bulky will increase your metabolism

20:56it'll get rid of the fat and the fat is a real problem because fried that will make you inflamed being fat is one of the worse things you can do just fat shamed I did were very very upset at you right now well build up muscle as well some people are overweight and have a lot of muscle and they're a lot better off when you you teach classes I assume I teach at Harvard yeah and when you say that fat is bad do you get a new reaction over the last couple years or do you do you find a way around saying it like that gen generally get okay comments on my lectures but I wasn't saying fat people a bad or saying having found in your Vice cells a bad right okay like were you saying so you're breaking it down to cells you're not picking on anybody yeah here at myostatin insufficiency produces 15% life extension in mice so yeah so those mile statin inhibitors make the

21:47mice grow longer so you think that might have had an effect by virtue of the fact they're more bulky and they have more muscle tissue and they burn off more fat that's one theory the other thing would be that some muscles are secreting molecules called Maya cons into the bloodstream and we don't know what they all are but when you exercise you do release some of these and they may also be contributing because muscles are signaling to the whole body when you go for a run it's not that your muscles get an exercise your everything in your body gets an exercise by these communication molecules hmm and that's why if you fuse an old mouse to a young mouse you can have these benefits that the young Mouse imparts on the old and actually negatively vice versa so when you say fuse you mean by taking the blood of the old mouse and putting into the young right but what we what we

22:33actually do because that's too hard you don't need humans but in mice what you do is you sew the skin together so that the blood flows between them yeah it's it's not so pleasant but they they don't seem to be too badly affected once they learn how to walk in sync now by the way to all your listeners we don't do those experiments in my lab but when I say we I mean yes to the scientific community as a whole your thoughts on if you have any about these startups that are actually taking the blood of young people and in injecting it into the bodies of older folks so I don't think there's a scientific reason to say it won't work and the scientists are involved are some my great colleagues very smart people you ever done it no that's a bit extreme for me but I think it could work right it's just a little bit out there for me but what they're going to do what they're doing actually is treating

23:32people with neurological disorders a lot of these startups you know I'm involved in probably 15 startups right now what we're trying to do is to treat diseases of aging and even rare childhood diseases because you can't treat it aging as a business model there is no disease called aging yet right but anyway getting back to the science I think that it's based on sold science but the future is is I think a better way to go about this is to find what the actual molecules are in the blood and just make those don't give the whole kit and caboodle yeah when you've said this twice you think aging is a disease or maybe perhaps should be treated as disease are classified oh absolutely think aging should be classified as a disease we should think of it as a disease I know why why shouldn't we everything else that goes on in the body over time that's bad for us is considered a disease do you know

24:25why aging isn't can disease because it happens to everybody exactly mmm that's the only reason well it happens to most people 90% of people in developed but why is that a reason to say oh it's natural we should just deal with it we used to say there about cancer and we used to say it about dying for an infection when you say it happens to 90% of the people in the developed world what happens the other ten they die hey pipe boss I guess okay I see what you're saying so they die young yeah okay just clarifying yeah I agree I mean it's been disi it's it's it's a problem right aging is a problem I saw an old gentleman yesterday and it was painful just to watch this poor guy walk you know hunched over and just struggling to move at an incredibly slow pace that seems like a person with a disease well it is and imagine if we were on a planet NOW oh you know an island where

25:17everybody leaves 300 years and we'd show up and you and I in our you know midlife we're starting to look old already they're gonna look at us and say what is wrong with you guys we need to treat you emergent Lee we need to call this a new type of syndrome right and it's only because we all tend to go through this that we think it's acceptable but I would argue it's the biggest threat to the healthcare system is the biggest threat to the world's economy actually is the inability of us to treat people in their old age and keep them healthy mm-hmm now some people look at it a different way and their consideration is that there's an overpopulation problem as it is and folks like you want to want to walk around living to be 300 years old have a gang kids you could create a mess all right well I have three kids but that's enough that's more than I was going to have but yeah it we do that you

26:15have to do the math though how much would the population grow and we I'm actually working with a number of people to try and calculate this number of economists in London that we're working on so this is this is really a problem I agree with you that if this comes and I would actually say when this comes when this comes is it I mean it's coming there's there's dozens of companies working on drugs the sciences here so let's say it's coming anyway so we have to deal with this how are we going to deal with it well let's first of all understand what the future looks like we can't look backwards alright because no one's ever invented this stuff before so we have to look forwards what's the world look like in terms of population it's not as bad as you might think if you stopped aging today and everybody just went on forever the population growth rate would be less than the rate

27:05of immigration now that's not I can't go on forever of course but what we find is as people healthier especially in developing nations they have fewer kids so the calculation shows that it would eventually taper off so human population will taper off about nine to ten billion people and then stay there and that population will be the happiest healthiest people in the world know why they predict that because I was having this conversation with someone the other day that as people become more affluent and society becomes more urban people will have less and less children and the population will stabilize is that the theory behind this right well actually education is a major part of it just watch yeah women's education is the main thing but also just being healthy or lifts the the wealth of a nation and by women's education do you mean extended education so that they pursue careers is

28:00that the idea or is it I mean obviously most people understand how babies are made like where where's the education contributing to a lower population well so my understanding is that the first thing you do if you if you educate young women is that they can make choices for themselves and they're not just subjugated you know most men would like to have more so right so you're thinking of like third world and write the real developing world but that's where the population is a real problem in Europe they actually are struggling to keep up with their population you know what they've got a an ageing tsunami so to speak same with Japan the average farmer in Japan is 65 years old they got a real problem China's about to head that way too and that's gonna drag the economy of the planet down and it's commit a real problem we gonna waste so much money on keeping older people alive for the last

28:4610 20 years of their life with dementia frailty that could be trillions of dollars just fifty trillion dollars just in country alone that could be spent on figuring out how to solve global warming better education the environment saving the the one third species that are becoming threatened that that's why I think tackling aging isn't a selfish act it's probably the most generous tax act that I could give the planet that's an interesting way of looking at it what populations as a whole you know when you look at the world what where are the people living the longest and why well it's debatable there are these blue zones I think many of your listeners will have heard about those but there are pockets that have great genes but they also have great diets and lifestyles and so the the best one that I'm familiar with is the island of Okinawa in Japan and and by the way I

29:41used to follow the Okinawa diet a couple of my good friends wrote a book about it so I was on tofu and some fish felt really great couldn't keep it up but those one can you keep it up I had kids and our meals turned into pizzas and hosta yeah unfortunately but I'm getting back there now that my kids are teenagers but the Okinawans they live into their hundreds fairly frequently it's not one in a million it's it's more like one and I think a hundred thousand or something so it's ten times higher they they work most of their lives they're physically active they fast a lot and they have a lot of green leafy vegetables and that seems to be the secret and there's a there were they were selling something was something about their mineral rich diet they remember they were selling it was like a big thing for awhile coral calcium and they were using that as an example of

30:33why the Okinawans we're living so long do you remember that I do remember ad yeah but in scientific circles we weren't really bothered with it yeah like there's calcium is calcium right yeah I didn't I don't know about it better calcium from coral or something I might even be wrong about that but I just remember reading about the Okinawan sand that the speculation they seaweed as well right very healthy probably the best thing that they do is they don't overeat mmm stop at seventy percent yeah I'm a glutton that's my number one problem I just love to eat yeah yeah me too I keep going once I'm in it I just want to just keep shoving it in my face but I've done a good job over the last few years of tapering that off and the intermittent fast and I think is probably one of the best things I've ever done in terms of you know just maintaining energy levels maintaining

31:26body weight that kind of stuff yeah yeah you look good so I think that that's one of the best things that people can do what we've known for seventy or more years actually is if you calorie restrict animals actually even heat cells and ones they live longer and this is the most robust way to to prevent cancer heart disease Alzheimer's in a mouse and so the intermittent fasting is just a way of mimicking this calorie restricted diet so what what is calorie restriction it's reducing what you would your doctor would recommend for your body but reducing it back to about twenty to thirty percent so it's quite extreme that's not pleasant I tried that for a week gave up too hard but intermittent fasting like yourself it's doable it's not always pleasant but I think that's the best way to do it and with the mice it works just as well as calorie restriction which is pretty much

32:16always being a bit hungry now one of the things are you looking at in terms of mitigating stress or like what other factors are there that you have to keep an eye on yeah stress is a bad one I try to take life in my stride not get too worried about it remember what's important so my heart rate rarely goes up even under a really extreme circumstances and that that's about it I try to balance my life as best I can I don't go through airport scanners as much as I can and have x-rays these little things do you think those are bad for you those are the new ones aren't they like a radio wave yeah they're they're millimeter radio waves I don't want to taking chances and also don't want to freak people out but the old-style ones that were banned in Europe first they've they were potentially damaging x-rays definitely try not to have as many as you can but flying is just as bad as an x-ray well

33:15that's the problem I was going to a scanner and I said I don't want to go through the scanner and they got quite upset because it's a bother but they said you know it's just as much damage to your body as the flight and so I said why do I want to double it anyway so I go through scanners but I try not to but let me tell you why I think it's so bad because scanners are going to change what we call the epigenome now a lot of people haven't heard of the epigenome the genome everybody knows it's your DNA the code of life the epigenome is what regulates and reads those genes at the right time okay and so we've we knew about DNA we know how to read the genome pretty easily we can do that now on a mars bar sized device in a day the epigenome is quite difficult different the epigenome is that the structure of how the DNA is looped around if you look at the chromosome you're not seeing the

34:12genome you'll really basically seeing epigenome and what what I think is causing aging is not that you're losing the DNA structure you're not having mutations you're actually changing the epigenome which is the the reader of the genes so put another way compact disc okay for the young audience compact discs are little things we used to put music on but anyway these are these are digital information of course and the reason we switch to digital in the first place is that it's very copyable and it doesn't wear out or as a cassette tape you know people our age know that if you try to copy that a thousand times there's not much left at the end so the the compact disc information is the genome the epigenome is the reader of the CD that little laser that goes around and what I think is causing aging is not the loss of the digital information but it's the reader at the analog part and that's

35:08like a cassette tape that eventually runs out what we what's going on really is that your cells are losing the ability to read the right genes the way they did when you were 20 and that's basically noise informational noise that gathers over time and so what we end up with when we're 80 is a compact disc or DVD that's scratched so the reader cannot read the right genes or time and the cells become dysfunctional now what we're working on is how do you polish that CD or that DVD to get that information back again and if you can do that I think that's really the best way to reset your age and I we haven't published it yet but we're working on ways to actually reset that genome and actually get back the information that we once had when we were 20 so what is happening to the epigenome when you're going through those scanners well so what we found is the biggest trap door

36:02of the epigenome is a a broken chromosome DNA break and I don't know about scanners that's just a abundance of caution but an x-ray will damage your DNA no question even going out in the Sun will do a bit of that and we think that the cells reaction to that break having to unwrap the DNA from its chromatin we call it and up and then rewrap it is what eventually disrupts the ability to read the right gene at the right place so DNA damage is essentially a little scratch on on the DVD and that accumulates over time so being out in the Sun does that but being out in the Sun also is beneficial your body produces more vitamin D yeah weld it so there's also a theory called antagonistic pleiotropy which is what's good for you when you're young comes back to bite you when you're old so you might look good and feel good and get vitamin D when you're young but the

36:54accumulation of these scratches on the epigenome ends up you know I'm formerly an Australian originally in Australia now American an Australian I grew up in the stratum son and I can tell you that you know most Australians look older than they should know Lausanne no ozone and lack of sunscreen in the 1970s why do you guys have a whole Nils on over Australia what's all about what you do know it's what what did the world - chlorophyll oh sure well hairspray why does it accumulate over Australia's or it started in Antarctica and so ozone will i've been convenient nobody's up there leave it up there yeah well if we need to please leave it below it that way yeah well yeah that the the ozone layer is fairly important if you don't want to get singed by UV light yeah well that's one of the first things I noticed when I went to Australia was there's all these Sun cancer warnings

37:52skin cancer warnings everywhere well a third of Australians get some form of kiss skin cancers that's crazy yeah but what's also gonna happen is it'll disrupt your epigenome over time and you'll look old but if you have an x-ray you're gonna damage your organs you're gonna accelerate aging I believe in your body and it happened you can't avoid double strand breaks broken chromosomes happens all the time there's trillions of cells in your body and it's happening all the time so living is a problem okay flying flying is even worse but we working on is how do you get back that original information into the cell and make a cell not just believe that it's 20 again but actually be 20 mmm so what do you do we reprogram them there are a set of genes that we we and others have found three main ones that when you put them into a cell or even into a mouse they

38:43become younger again whoa how far do you think you are from implementing this on human beings well so theoretically you do it to yourself you could you could do it to yourself theoretically I would I wouldn't do that cuz I'm not crazy we need to figure out the safety I don't want to become a giant tumor well we just use it on bad people uh yeah well I think people know to throw tournament ooh 18 year olds and go whoa yeah well yeah that that would be for someone else someone else well hopefully no one would ever do that why not well what kill them is what we're doing I agree with you that we want it we want to see what happens in your hands you just give them like free pizza or something they're on death row right if you're there already murderers you want to be the first one to me come on my live death row and I want to go on to death row but I'm saying if you're gonna

39:35kill somebody like wouldn't be a good idea to like oh hey we'll give you four hours of TV a day so we want to shoot you up with some stuff it's gonna make you younger if I was on death row I'd go do it see what's up I don't watch TV well what we do is uh so we give it to old mice and we check it what happens to their body so nursery people do it to them right well tell you what I wouldn't force anyone but if somebody was blind or almost blind yeah and he now studies we're recovering eyesight really yeah what about two damaged eyes yeah really yeah so I don't want to freak out because I know a guy who's got a significantly damaged eye from fighting well I can tell you what we've done and this is what we're riding up for publication now we've done a few things three things to the mice one is we've pinched their optic nerve and crushed it which was a test for growing neurons in

40:35AI and we find it with our reprogramming we can make the nerves be just like a newborn baby they grow back and then we also tested on glaucoma pressure in the eye we increased pressure in the mouse's eye and they lose their large litre eyesight and we can recover that and then we also a test old mice that don't see very well and we also seem to improve their eyesight almost back to normal so what I I don't think we'll be going to nursing homes anytime soon but what we are doing is running a clinical trial on this and so we're looking to do that in early 2020 and the clinical trial will be on people with glaucoma or various eye issues the plan is glaucoma first but it could work for other damaged retinas as well even broken spinal cords what we're thinking of trying Wow and that's just one part of the body imagine what it could potentially do to the rest of us do you

41:26feel incredibly fortunate to be living in this century I do every day but I would love to live next century because it's gonna yeah but your what's cool is you're kind of at the tip of the spear pushing this stuff right now like you you're gonna be one of the guys that gets to see the stuff get implemented from your actual own research where it didn't exist before yeah that's pretty damn cool better than like living 100 years from now where you just take it for granted like a trust fund kid you know yeah but just imagine what you can do in a hundred years you can write well maybe you'll be here we're all on the yeah you might be 150 we'll see yeah I think there's a chance someone will be well it's it's a good chance you're gonna be I mean you're the one who's gonna know well so he's my philosophy I'm not gonna let anyone try technology until I've tried it first really so I was taking an

42:24Iranian pause because you're you're currently doing something like that I'm not doing the three programming yet that's a little dangerous but the others I've always wanted to know first my eyesight is starting to go cuz I'm 51 now and like when I'm like if I had to read this book I got a NIC Christakis this book if I'm sitting here reading this book if I don't have reading glasses on I got to do this it's a bit of a struggle gonna be able to fix that so potentially in the mice we can you can we well I don't we don't give them books to read but their eyesight improves we can test that how do you do it there's a moving screen no I don't mean how do you oh how do you know how do you test or not not how you test rather how do you improve their eyesight we've we put these reprogramming genes into a virus which is already used to treat genetic diseases in the eye and we

43:13inject it straight into the mouse's eyeball this sounds like the beginning of a horror movie yeah I think it's actually or an awesome movie it's the awesome part that I'm so pissed on well if you're going blind right one injection from your doctor and then you take an antibiotic to turn the genes on for as long as you need and you get your eyesight back that's not horrific at all that's a pretty incredible how far away do you think you are doing that to humans well 2020 will be the first safety study we hope yeah but the crazy stuff the future is if this all goes well you have an injection in your vein let's say when you're 30 and then those viruses infect your body and they sit there dormant until you need them so when might you need them you might have a car accident turn them on you can turn them on with just a an antibiotic in a drip or in a pill or you start to lose your eyesight

44:04take it take an antibiotic so you put them in your body almost as an insurance policy and then you have the option to turn them on in the future exactly Wow it's what we do in the mice now with every action we assume there's some negative consequence or potentially negative consequence right we always assume that but it's not always right mm-hmm so it with the molecules that we've been testing for years now like in oh man we haven't seen any downside just longer endurance and protection so there isn't always a downside to these things in fact if you just think n MN is replacing a molecule that we lose over time as we get older it's just becoming you know it's a fairly natural process no downside exercising and dieting either right of course and you said you run once a week is that what you you and you do do you lift weights as well right and when you do it do try to not go too

45:03hard and burn yourself out too much do you have a sweet spot yeah I do I do I try not to go too much all right that that's the trick with everything in life mm-hmm it's this so hormesis effect to get your body damaged enough that it can repair itself but give you the benefits without like having a lot of x-rays or radiation we're out doing it and scratching that CD yeah that's always my thought on people that do extreme endurance activities like ultra marathons and things on those lines I mean I marvel at their willpower and their ability to push themselves through that and the the physical condition they have to be in to perform such feats but I always think man you're probably doing x times the amount of damage to your body that a normal person does at your age it sounds right calorie restriction works but if you overdo it you also starve you yeah you die so you got to

46:04find the right balance right how do you how do you know what the right balance is for you good question how does anybody so we live in an age that is still fairly primitive this is why I like the future these days we go to the doctor most of us go to the doctor for annual physical which is ludicrous the idea that your doctor will take a hopefully a blood test or prostate exam once a year that's kind of crazy what happens if you've got a tumor that developed the day you leave the doctor's office so the future and actually partially for those who are on the cutting edge can be done right now it's monitoring your body in various ways genetically epigenetically we can measure those scratches right now and also with blood tests you can also have companies tell you if you're out of range if you're not optimized and how to get it back in order so that's what I do so how often

46:58do you monitor your blood probably every few months I have a blood test from a company that tells me what I need to correct and how extensive it is is this blood test like is it a standard one that a normal person can get or do you have to have a prescription to get this or no you can go online and get it it's about I think forty parameters they measure some that are not standard that your doctor wouldn't do some are pretty standard but what's nice is it's it's a tracking system it's called insight tracker and they you can see over time if things are going up and even if they're not out of range yet you can see if they headed that direction and correct it before it's too late so that's why one of the reasons I'm on metformin my blood glucose was going up and up and up which predicts lower life and some metformin got it back down to where it was optimal again so that's one

47:43of the things in metformin does is it lowers your blood glucose that's what it's prescribed for for diabetics mmm now does that have any effect on your energy levels I don't think so I haven't noticed that hmm where you would notice it is during rigorous exercise that makes sense do you feel it uh well so I take med Forman at night so that maybe probably the best thing right so when you're sleeping it's having its effect and it's run its course by the time you wake up you play yeah hmm now when you you are exercising are you exercising fasted or do you take certain amount of carbohydrates before you do any kind of physical exercise so I start the gym to 2 p.m. on a Sunday and I'll have a salad wrap or something like that so I'm not feeling hungry during it and one pass out huh and so I understand you're getting these blood tests but do you have a trainer do you do set a workout

48:43or you structure it I do now just recently go to trainer it's great thing to do with your son father sometime so yeah that we have an hour of trainer and then we we also do a bit of boxing and the mix it up you're beating your song up yeah it's fun it's legal I think go to the sauna and that's just the best way to spend a day that is a nice way to spend day so how many days a week you doing this so you do give yourself days off do you you schedule that well it so once a day of that I once a week on Sunday enjoying the week if I have a chance and I'm not traveling I go to the home gym and when you say you run once a week is that by design that you only give yourself once a week I probably run two times a week a high intensity if I could and I try to do that often I'm on a plane or hmm right and we say high intensity are you sprinting doing track work like what

49:41kind of stuff yeah so I'm not an expert so what I do is I I will enter hop spend a half an hour on one of those treadmills that you shaped mm-hmm yeah yeah great they are so that you determine your speed so I'll sprint and then I'll slow down and sprint slow down they're actually more difficult than running on the flat surface it's where regular treadmills is actually easier than running because the treadmill is moving you just kind of lifting your legs up and keeping moving with this actually you're powering it so by you pushing on it it's actually more it's like running I forget what the degree incline is but it's like an X X amount per centage harder than a regular run oh good well that's what feels good to me and what although it's a little bit scary if you're not used to these treadmills you can run off the front because they're free-flowing go it right

50:29off the tip they have handles oh yeah you're a genius you're not gonna go flying off the treadmill again dummy I'm no genius especially when it comes to sport well yeah yeah I'm a big fan of those things and it's nice too because there's a lot of give to them there's not much pounding when you run on those it's not like running on hard surface yeah so I tried to go easy on my joints I've seen you've probably all seen sports players with all sorts of damage to joints and I've done all of it you know yeah so yet low-impact high intensity hmm and as far as weight lifting what kind of stuff you do in there cuz weight lifting does have a beneficial effect on bone density and it's supposedly has an effect on anti-aging as well yeah absolutely believe in that and so I try to maintain some muscle mass it's good for burning fat too so you know I try to do not go overboard with the bench

51:27presses otherwise I'll have even more rounded shoulders estrella get the straight back so the trainer is helping me bring my body back into shape you took one look at me and he said you you you did this unsupervised yeah you wrecked your body in your 20s let's try to fix that what did he say you were doing wrong I said well why would you do an exercise on a part of your body you can't see in the mirror oh you're back up my back is is flimsy and it's all it all here so I said like you're a smart man it's protecting your spine you but I love bench pressing Oh God at least I used to sorry I'm one of your shoulders out too though right oh yeah yeah especially if you do it heavy now you do this how many days a week hopefully two or three two or three a week so all everything you're doing you would essentially recommend to others as well right so do you think

52:17that's a good plan two to three days a week of weightlifting one to two days a week of running well honor when you can yeah so I I'd never used the would recommend gets me into trouble yeah good move I just say what I do when people can judge but outsmart but the science does say this is the optimal and that's why I've chosen it for myself but I think without monitoring yourself it's easy to overdo it and also you just really don't know what's going on in the inside it's crazy to think we know more about our cars as we drive on the dashboard than we do about our bodies how does anybody know if the exercise is too much too little or if that supplements doing anything right with that that is a big problem right I mean one of the things that we have a giant problem in MMA is tainted supplements people buying supplements the supplements have other things in them

53:05and what are you drinking do you drink mostly water to consume caffeine so with any man which gives me a boost I think caffeine's a little too intense really I find that so I'll have a cup of coffee in the morning but that's it one one a day yeah Wow yeah just two kicks I don't live it's hard it's really hard right when you're doing research all the time don't you need a little boost sometimes well I do drink I cook oh oh how dare you I'm just ruined everything you said you're doing that yeah it's - horrible for you is it that bad house for teams well I actually had an inflated idea of how bad it was apparently but in talking to another research scientist he was telling me that the this the actual amount that they gave to rats when they're you know diagnosing them with cancer is almost impossible for a person to consume well so you'd have to have ungodly amounts of

54:10aspartame in order to get these effects that everyone's terrified of he said the other thing to take into consideration is look around at how many people are drinking diet coke he goes it was really that bad they'd be dropping like flies the the consideration though is upsetting your gut biome right now that I know or at least I've read but he said that's also probably large quantities uh it's true but as you know the microbiome is a finicky thing you don't want to mess with that's the reason I have this this yogurt in the morning trying to research kimchi at all yeah not regularly but yeah that's that's what about other fermented vegetables or anything along those lines probiotics Japanese food I mean - but I don't think about my diet that often mmm usually too busy running around but now have you ever messed around with nootropics or anything like that to

55:03enhance your mental clarity or boost your brainpower what well yeah my brain is always running a marathon that's where I definitely noticed that if I take time off even a weekend without thinking I'm Dumber on Monday dumber well yeah I just can't really so like it's almost like you need to keep that case going for sure right rights good I guess I'm not a natural genius I have to work at it but I do find that that constant stimulation I've got to do that to be at the peak and this is the tippy peak this is the genetics department at Harvard Medical School these are no dummies these oh yeah what are them a Nobel Prize winner is an you got a I'm a lot of the signs we publishes in the world's top journals which you really get into so to be able to think of these ideas and come up with new things you can't just do that on you know on a whim you really have to have a

56:00mind that is focused and in shape exactly yeah so it is essentially you feel like running like you take days off you actually slip back a little bit and you have to ramp back up these horrible I really hate it but is it just because you just get used to a lazy pace and you have to like acclimate to get back in the lab or is it actually you do get dumber I don't have the memory recall I feel like I did when I was in my 20s which is I wasn't as sharp I'm a lot sharper than I was then so part of it could be the mental training that I give myself every every day the other part could be that the molecules that I'm taking so in a man raising nad could have new rhetoric effects we don't know yeah I'm sure creatine supposedly has nootropic effects as well do you ever take that no caffeine certainly does I'd like to get you some actual nootropics I'll send you some there's a bunch of

56:56different ones that I use I use three different companies one that's one of mine and to the other companies neuro one and another one called true brain and I find them pretty beneficial great I could do with that yeah it'll definitely well the one that we've tested was alpha brain we tested the Boston Center for memory that did a double-blind placebo-controlled study showed increase in verbal memory increased reaction speed reaction time but the the other ones piracetam of your mess with any of those no choline you supplement with that no interesting right I could be smarter I guess well this I don't think it's that it's just it's it's not smarter I don't think anything makes you smart I think knowledge makes you smarter what it does is gives you access I think to something that's already in your head good a little bit a little smoother good the recall is important the other thing

57:52as a scientist what you need is you need to see a thousand different sets of data and put them into one thing and see the connections mmm so I'm exposed to so much information it's drinking from a firehose every day I'm reading papers I'm talking to dozens of people I've got dozens of companies got two labs in the world it's just coming in and for my brain to take it in sorted out finds links between them connect that person with that politician with that person or military it's all going on and a regular brain that isn't trained would have a hard time yeah I would imagine I'm so shocked that you only drink one cup of coffee a day with that kind of schedule well so the nmn is good do you take nad in an IV form no no I've I haven't but I've talked to many people that have I've been scheduling it or wanting to schedule it putting it off for weeks but I'm gonna do that soon

58:47because I just know too many people that have extreme benefits from it yeah it sounds good do you know anyone who has done it no hmm that seems like something will be right up your alley yeah you'd think just be more focused on curing aging hmm but nad does have supposedly some sort of an effect on Aging correct IV nad I don't know about an IV and eighty else it's being poorly studied actually as a lot of anecdotes and I hear about these all the time but I haven't seen really hardcore double-blind placebo-controlled trials now nad in supplemental form though in in terms of oral orally ingested nad well so if you give an ad to an animal or a cell it taken up really poorly nad is a big molecule mm-hmm n MN is a smaller version of nad that gets into cells quickly so that's probably a difference so it's the same benefit but it's easier consumed orally well I think

59:51so I mean the we're still at the cutting edge of figuring out what's true and what isn't but nad is thought to not be well absorbed in the body as compared to these other smaller molecules that the body then turns into nad once it gets in how much water do you drink not enough not enough was just speaking with some members of tombe Tom Brady's team and they said David you gotta drink more Tom Brady's team uh yeah you mean is like physical team you know like the Patriots know his uh his CEO of this company okay and they're saying you need a drink anyone got to see it's like suggestion I'm good drinking something yeah I'm drinking a lot more alright then you end up just going to the bathroom off the time but go do what you gotta do you do you know it makes sense to me having a buildup of toxins in your body and urea isn't a good thing right um do you take anything else

60:46the is notable well I can run you through it sure I'm on a lipid no a statin for I understand I've been on a statin since I was in my 20s whoa yeah hmm that stuff's terrible for you uh right so my good friend and colleague George church at Harvard told me I'm killing myself but I have really high cholesterol my family genetically genetically yeah and does your family have a history of heart disease because of this yes my grandmother at least according to her had a stroke in her 30s and then yeah it's it's bad so I'm I'm fighting bad Ashkenazi Jew genes here that's crazy see but on him since you're in your 20s that's and you're a thin man if anybody looked at you they would never think that you would have an issue yeah it's unfortunate um but I'm a doctors worst nightmare first of all I teach them so I know what they're like but also when I go into the doctor's office I say here's

61:45what we should be doing oh you should be doing to me and I saw when in my 20s and I said I want to go on a statin and this is in the days when statins weren't well studied and my doctor said but you're not old and I said I don't want to wait till I'm old and sick to get this medicine I need it now and I thought the doctor for the doctor and eventually he prescribed it and my cholesterol came down I'm the same with dentists I went to the dentist a few months ago and I said I want my teeth fixed my two front teeth and she said they find normal wear and tear and I said I don't care what's normal fix my teeth get them back to how I was when I was 20 no we don't do that we don't do that well you did my daughter right last week yeah but she's young she's got a future oh hell done don't be ages wrong with your teeth are though wearing out and I hated feeling that worn out we're a cow

62:34you don't get that way uh just getting shorter and flatter and what the you eatin rocks yeah I must be the Australian diet sand in your food yeah so I said to her I thought you were one of the world's best dentists and she said okay fine I'll do it but don't blame me if it doesn't work and so she's worse well she was worried that it might snap off so you she's putting a cap on you yes she's extending my two front teeth which is normal like people get caps all the time well it's not a cap it so I'm actually just material stuck to the tip right just on the tip yeah it's and oh so like if you had a chipped tooth they would do that instead of replace the actual that's what they did to my daughter yeah and I said do that to me that looks great and she said no no no finally she said okay but it's your problem you got to pay for it fine and she did it and she actually

63:29said at the end of it this is great I might offer this as a procedure to other patients hmm but but my point is not about teeth it's the medical profession is ageist they give young people certain treatments because they're young and they don't give them to the old but then they don't give the young people the treatments that they need before they get old yes wacky I had a similar thing happen with a torn meniscus I have a minor meniscus tear and the guy told me well if you were young they would stitch it up and hope that it would heal I'm like what the does that mean I go everything works good like what is difference what is the difference between me and a younger body and he said something about blood flow you have more blood flow I said look I'm not a doctor but that doesn't make any sense I go I'm working out all the time there's a lot of blood going through there like

64:20what the is happening and I'm like let's just shoot some stem cells in there and see what's up because they wanted to do meniscus you know and what is it - copy whatever they call it when they cut some of the meniscus out I'm like yeah let's just let's just try it it's totally working like I don't have any pain in it now so um I think there's a weird thing that they do do when you get to a certain age like yeah like I have a friend it was a torn ACL and they essentially he's in his 50s like little late 50s and they essentially told him not to fix it I go hey get it fixed we crazy and I have a wobbly knee and they're like well he told me if I was younger I that doctor go get that thing fixed he's like well how the recovery time like shut up you just recover you just alive a year goes by it's fixed just stop just go get it fixed yeah see that's the problem with today's society

65:15because we think a 50 year old is is okay oh that's dead that's BS 50 is still very young actually there are 78 seven-year-old 80 year olds even now you're all still playing tennis yeah loving life that's that's just the beginning of what's coming if you maintain activity that seems to be the key the the really hard thing is once someone's in their 50s and they want to get in shape now and they haven't been active their whole life that seems to be a problem there their DVD is scratched up yes hard to go back it can be done though I did see a guy who was 58 years old who started running marathons at 58 in his 70s he's running sub three-hour marathons and he looks great so it just he just had to take his time and really be dedicated and watch his diet nutrition and next thing you know this guy's an elite marathon runner it is doable what we find in the lab is if we

66:09treat my Serle in life it gives them the battle much better lifespan it's sure so don't ever leave it too late well you see that with athletes like athletes that were fit when they were young and never lost it really maintained and stayed in the gym and stayed active you see them in their 50s and even their 60s looking great whereas you know it's just once your body deteriorates it's very difficult to bring it back but if you maintain it it seems like there's people today that are doing that it's much more common if you go to a gym for instance go to a nice gym you'll see a lot of folks that are in their 60s and 70s that are really active and they're there all the time and the regulars have the gym and they look great they do somewhat my father is a is a prime example of that so he's in Australia and he's been taking care of his body since he was in

66:59his early 40s probably a little too late but still he's been taking cementum and it's metformin for a while resveratrol but he's been active that's the key I think and then so that combination so he's now just turning 80 this year you would think that he's 30 if you if you didn't know his age and he's running around my mother passed away from cancer so he's dating women he's out every night he's traveling the world now this is the future for for people in their 80s he started a new career at 80 it was at 76 what's he doing he got bored to retire at 67 thought he had another ten years of good life and he kept going and going going his friends are getting frail he's still active so he went back and he's working at Sydney University on the ethics panel for clinical trials and other studies and that's what you want older people with wisdom and knowledge to do to get back that sounds good too

67:59like for you you get your dad hopped up on all these awesome new drugs then you get them working on the ethics panel for clinical studies and then you get them to give you some death row patients so you can try it on right you're on to me yes I know what you're doing now man you wiggle in the system a little bit will you keep it in the family hyperactive super healthy dad right well I don't recommend anything even to my family but they end up demanding it my brother was somebody upset that we weren't giving him any well it seems like it's working out really well for your father I mean sodium metformin the NMM and what else is he taking he's also on a statin and he exercises that's the main so he's on a statin as well because he has the same predisposed condition you know right that's an awful condition man that mean one of the things that I was talked

68:51to my doctor about he's saying that that there are people that just have high blood pressure or higher you know higher blood pressure or higher instances of heart disease in their family and it's just a really unfortunate genetic issue it is it is but fortunately we were able to tackle heart disease pretty well yeah these days with blood pressure drugs and cholesterol drugs you know there were some side effects no question but what we're talking about with these longevity drugs that are in development is that sure you can be prescribed this medicine for your Alzheimer's or if your liver disease but as a side effect it'll keep the rest of your body healthy as well protect you against cancer and all these other things that's what's so radical about what we're doing hmm now what about CRISPR and what do you think is going to come out of that in terms of like real-world

69:43application for an adult I mean what if people don't know what Chris Perez please explain it in layman's terms yeah so CRISPR is a term actually was invented in my department partly so I know it pretty well it's back bacteria have an immune system that cuts invaders because their DNA and what we've done now as scientists we've now utilized that system take it out back to you and we use it to create designer mutations designer gene changes in animals and also in humans so it's a bacterial immune system that corrects genes and we use it all time now it's um it's it's actually what's interesting about being able to mutate genes for many years but this is dial up a gene mutation you can choose exactly where you want to make it and so I think many of you Lister's will know that recently late last year Chinese researcher in our field came out and said he's engineered a couple of

70:42twin girls with CRISPR to be resistant to HIV the AIDS virus Wow um if they're telling you that you got to think they're doing some stuff they're not telling you about right well yet have some with giant heads and well it's coming through walls yeah and well yeah if you start to see people that are 90 and and they're still as young as 20 you know something's going on yeah that's the weird one right if you can you go hey what are you doing nothing just eating healthy looking good take care of box all right we're not gonna tell you yeah yeah well so consider this that that so the chance of getting HIV in China is one in a thousand so that doctor was seemingly he thought he was ethical protecting the babies from something that's I would say really rare right whereas if you really wanted to do something helpful to those kids and we agreed it was it was something

71:36you should do why not make them resistant to heart disease or to cancer right we can do that it was weird that he chose HIV is the first test why do you think they did that um I think because that it was a very well understood mutation that would if you just destroyed the gene it would work or as with these other diseases you have to be much more precise but the reason that we scientists got really upset was that he did it in secrecy and then just launched it on the world and that kind of thing because that it's a fine line in ethics you want to be doing that with total transparency I mean I think he was hoping to become win a Nobel Prize or be a star and it backfired on him because he just did it in secrecy it backfired in the scientific community absolutely in the in the real world in the media I was shocked how little discussion there was if this news came out in the 2000s

72:30during the Bush era it would have been panels investigations that would have been in news for months but it wasn't people went what's next on Twitter do you think it's just because the news cycles so insane I do yeah when you have a scientific experiment of that nature what's the standard protocol for a scientist whether it is or is it the same in China and in Russia and the United States as a scientific community almost operate under different like a different set of rules and anything else you mean between countries yes I mean you know like obviously technologies not shared like China is doing something technologically the United States is they we have to speculate we have to figure it out but when it comes to medical science right is it sort of an open book because everybody sharing information I know or at least alerting everyone to what they're working on well I know you're

73:30going with this at least I think I do yeah yes I I advise governments around the world about what's going on under the radar is my best I know and there are countries I'm not gonna name them that are doing research under the radar and are preventing people like myself from entering those buildings to have a look what's going on yeah so I'm sure that what's going on in there is actually a little bit broader you know we hear about but I don't know how long is it before just say Russia no I didn't say Russia I didn't say anything no country I want to be able to travel I really a Russia but I said it but in in in countries where there are different standards what's stopping them others who wants to prevent their child from having heart disease which could kill their child you know 40% chance versus one in a thousand and eventually you could make a child that could live 200

74:28years once we know how to do it that could be the future there's always a concern that someone is doing something that is beneficial in one way but negative in another way and if everyone doesn't get to examine the research it's very difficult like if we wanted in the United States wanted to do something similar to what they're doing over there we would want to have access to what they've learned right we would and so generally scientists share information right but there are companies that are government-owned that are very secret right or even private organizations and that's where it's a little tricky and that's why we we scientists get really upset when companies or organizations don't share information especially on something that's critical right and what's not really stated but it's my belief is that one of the reasons there was such a backlash

75:22this crisper design a baby experiment and it really was an experiment it's not just that it was potentially dangerous and you could end up with kids but have deformities but also that unless we do this in a in a measured manner under supervision there's there could be a backlash like there was against stem-cell research you know in the 2000s we don't want that again we want to be able to do this the right way this time right is it particularly if something goes wrong with those children one person could ruin it for millions of right if they jumped the gun and yeah so this we're on the second generation of crispers are correct in terms of the editing tools they've become more they have that there's there's surprisingly that there's a lot of different bacteria that have these systems so we're getting new ones all the time some that are more accurate because you don't want what we

76:17call off target effect you don't want to accidentally mutate some gene that's required for head development and so yeah well I think in my department we're on fourth generation fourth generation yeah Wow yeah see I'm just going by Radiolab podcasts yeah so my departments a fun fun department to be in imagine they are in the ending all sorts of stuff what did you ever see the documentary Icarus oh yeah rings a bell it's Brian Fogle's documentary on the Russian doping program state-sponsored doping program and Sochi the Sochi Olympics and how they this incredibly complicated system of stealing the urine and putting it through a hole in the wall and putting fake your and back through it was really really amazing amazing amazing documentary but details this incredibly complicated state-sponsored doping system I would imagine that with something like CRISPR

77:19or some various new forms of genetic editing that that's one of the things that they're going to be looking into that they're going to be looking into things that are going to enhance athletic performance yeah you might need to have a DNA test to see if you've put one of these viruses in your right why you 50 and now you're running like a 20 year old right so that's all possible you know that the I also write reports for for governments and one of the things that I predicted 15 within the next 15 years was CRISPR being used to engineer the human genome and make a baby I didn't realize it was gonna happen within one year well a lot of these technologies that I'm trying to predict happen way faster than even I think it gonna happen do you think it's possibly happened in other circumstances that they're not going public with it's always possible there may be some human

78:15clones running around right now that we don't know about do you think so it's certainly doable scientifically there might be some rogue nation who's doing it barbra streisand's talks or we're pretty easy to clone yeah she had her dogs cloned right yeah yeah Sammy the fourteen-year-old dog is now there's two of them oh Jesus Christ it that is so weird that because I'd be so scared I'd go to sleep and wake up that thing would be hovering over my face with red glowing eyes yeah wait till you have design a cemetery what what a friend of mine comes put some on Tate Stanford we're entertaining the idea of making dogs live longer genetically so why would you want your family member to only live yeah 12 years I think about that man my dog is only 2 and he's such a sweetie you know I'm sad that one day I mean I had to put my other dog down recently and who's 13 and just really who's a

79:08mastiff too and he was struggling and I just think man this two-year-old one day he's gonna be in that same sort of situation well it is and so we have three dogs my wife runs a therapy dog okay Barbra Streisand had a beloved dog Samantha cloned that crazy look at her two copies of one dog Jesus Christ that's so strange how about just get a new dog you nut well so it some we might be nuts in my household because we're giving out dogs in a man oh and how's it doing how old's the dog so good what the oldest dog is nine and he's still doing fine Oh does he look different uh my wife says so these are anecdotes I'm not gonna publish them but so Alice's a therapy dog and he has to go to hospitals and nursing homes and if he has any men according to my wife he can't be a therapy dog because he's too excited he's running around jumping around really so that that's anecdotal

80:00but that seems to fit with what others have experienced too Wow yes we're hoping to have some treatments for some pets shortly one of the companies that I'm working with treatments for pets yeah well you got to think hey man dogs going to live 13 years anyway you know well yeah and also we have a dog that has a kidney defect and the vet says it's only gonna live five years so she's three now so that's the one you're experimenting on well we experiment on on it on all of them but um but what's the downside that's gotta be so uncomfortable for some people listen just right now I don't know how to feel about that right what is the downside if your dog has got a kidney defect and it's only gonna probably live to be nine meanwhile that dogs gonna live to be a thousand years old well let's say I'll come back like you know be in the lotus position meditating 100

80:53years from now what do you do if it starts talking to you that'd be great yeah what what do you do if you turn a dog into some new kind of thing that lives thirty or forty years what do you tell people like if your dog like right now you're talking about on the podcast and a bunch of people are probably gonna remember but a lot of people forget but if like 15 20 years from now your dogs still chasing balls and we're gonna come over your house hey Dave what the going on with your dog man right stop the same dog that's Charlie yeah how come Charlie doesn't have grey hair anymore man right well you know people don't have any gray hair no yeah man that's weird isn't it you know of any that's weird right how long been on this stuff well drove our trolley started 12 years ago mmm it Foreman about three years ago and a man about the same time Wow does anyone in

81:43your family have gray hair is it a genetic issue my father has old gray hair my brother's about 1/3 Cory off grace Wow as your brother taking the stuff you're taking only recently uh-huh interesting yeah we call that an N of in an experiment which is insufficient right so I don't want to get slapped on the wrist by medical schools on society who's saying all these things you're just answering questions sir do not worry right but so far so good if I'm around in another 100 years we'll know something's odd that would be unbelievably fascinating if your dog lived to be like 30 or 40 years old that would be really incredible and if I meet you in 15 years you still have dark hair I'll be like what what the hell man what are the things are you taking do you take multivitamins I take vitamin D that's it with k2 just vitamin D yeah what about E or K or any of those k2 and

82:45D together and that's it Oh hmm so I'm afraid of iron rate of it yeah why there's some results that I've seen that that excess iron especially in the elderly leads to senescence of cells and buildup of those zombie cells is a bad thing and is this dietary iron like from vegetables or is it from cooking on a cast-iron pan or well I only know from correlations so I'm looking at tissue that's full of iron and the cells are not looking good so all I can think is I don't want to overload my cellphone R so this is like hmm how much iron is too much iron we don't know yet because I always hear it especially from women the iron deficiencies for some reason I hear I've heard it from several women sure but for the elderly overloading them with iron I think is a real problem so there's a sweet spot to hit well yeah I'm sure I'm sure there is but the iron will will damage your cells pretty badly

83:49so you don't want to go overboard mm-hmm and no other supplements now I try to eat vegetables which hopefully will right make sure I'm not deficient in anything green leafy dark vegetables exactly exactly that's fresh if I can colorful straight out of the fridge instead of going for the four a piece of cooked meat I'll go for a carrot or something late so many carrots I probably turn orange no carrots have a lot of sugar oh great now got to cut out my carrots well I mean especially if you drink them in the juice form like I know a lot of friends who really enjoy fruit juices and vegetable juices and I always say well I mean that vegetable juice yeah it's probably great but fruit juice man drinking a big glass orange juice you might as well be having a coca-cola yeah yeah I agree so our household has a ban on smoothies and fruit juices and so does that have sugar in them I used to

84:49be able to go to like Jamba Juice and get one of those big ol smoothies and feel like you're doing something good for your body I used to think yeah look at I got all this blueberries in there and great stuff but meanwhile there's just a gang of sugar in that thing yeah I heard an interesting thing that that whole milk is actually potentially better for you than the low-fat oh yeah you'll use less of it and it doesn't you know milk has some sugar in it it's also attached to fat right the whole milk has fat in it it's normal it's normal for your body to cross movement that way right what what I want is I want my money back from the nutritionists in the 1970s and 80s I I skipped eggs and Bakey I could have been eating that stuff well you remember that food pyramid that used to be in the dr. Seuss books you're teaching kids to eat cereal you know it's so crazy and I

85:35put my drain on your bread oh that's the best that's the the best bad advice that they ever gave vegetable oils which are terrible for you all those disgusting vegetable our and corn oil all that stuff that's just terrible terrible for you it is the other thing that that mothers used to and to some extent still tell that kids is don't go hungry have a snack yeah I shouldn't say mothers parents in general but in my family it's it's my wife she hates to see our kids go hungry at all right so it's always 888 never be hungry and I'm there saying no be hungry it's good for you and it's this the same with children though because children are growing I always assumed that children did you just eat whenever they're hungry well that's what stated I'm not sure if that's the case often my son is somewhat my son isn't then put it that way and he'll we going out the door and my wife

86:33will say have you had breakfast no I'm not hungry you have to eat something and I'm thinking no you got plenty of energy stored there don't worry about it yeah I mean it makes sense the only thing that I think of is that when you're a young person your body is still actually growing and developing as opposed to you and I if we're fasting it makes sense right it makes sense you're you're giving your body a break and there's all sorts of proven benefits to that fasting process and well if you have a child who's overweight it is it a bad thing to skip a meal no no it's not the one-day thing that worries me about children that are overweight skipping a meal though is that they're not as disciplined and they're not so good psychologically with struggling and and having you know having hunger pangs and that you're gonna their head up it's great the teachers will probably be

87:29very angry with me that the kids can't concentrate well it's not just that yeah the kids can't concentrate but I just I worry that it's in some way shape or form abusive like to say hey you're overweight you need to lose weight like I don't think they're like I don't think they're really designed to go without the way way a grown adult does these are my own perceptions I think that it's probably far better to adjust their diet and if you've got a kid just slowly get their body weight down with exercise particularly with resistance training and doing things that really burn off a lot of calories and then just get them off the sugar and then I think the way it'll slowly slip off probably not even so slowly if you can really get them off a significant sugar binge exactly so that's why I'm taking my son to the gym as well I agree with that yeah I'm just just to clarify because I

88:23don't want a bunch of hate mail all I'm saying is don't force-feed a kid yes yes yeah don't force-feed a kid yeah I agree with that but I just think that kids they just get so hungry man they get cuz they're out their little bodies or like little hummingbirds you know they're burning so much energy yeah they do I'm amazing you don't take any other supplements just vitamin D no multivitamins you don't want to like cover all your bases no whole food supplement like vitamin or a plant-based supplement that you could take during the day no none of that um you know I'm subscribed to the idea that a lot of its expensive urine and you know I'm testing myself so I know if I'm deficient in something bad and all my vitals are close to optimal mmm so something's out of whack oh I'll see it probably so you were saying you'd do things for the government what do you do did I say that

89:22yeah you said that earlier you said I should ask you and I didn't he did man even before the show started I was outside um I was feeling frisky now that I've thought about it it's time to go to jail well talk about the get you in trouble so let's pause and think this for a moment the things you can't talk about please don't there's a lot to talk about I just have to make sure it's nothing that's confidential but there's a lot of interesting stuff going on on the planet there's there's areas of bio defense that are pretty scary so some nations are apparently working on using CRISPR and other gene editing systems and modifying bugs that could wipe out a few hundred million people pretty quickly what do you do how do you detect that even the flu that's a massive bio threat and it may just be natural and that could wipe out another hundred million people like you did

90:19exactly a century ago so I'm work on that stuff detecting viruses wiping them out cleaning a room of DNA making sure that everything's clean I'm so I'll give you an example so that the Navy SEALs came up to my lab and they'd like to ask our group to solve some hard problems and so the problem they set us on was how do you kill anthrax say right now it's very difficult to kill of course when the anthrax letter was open in the Senate what was it a number of years ago it cost 25 million dollars they had to seal it off and put our Jim peroxide all over everything destroyed the computers so they're wondering how do you kill anthrax safely so that you don't have to be in a hazmat suit to do it and so what we came up with after thinking about it for about a week was we need a biological solution not a chemical and we found a an organism that where its whereabouts I cannot disclose

91:20but it's a very interesting organism that grows at high temperature and it destroys all bacterial and viral life and it wipes it out and it doesn't hurt humans at all you as or at least in animal studies you can breathe it in you can put it anywhere and it's fine so this is a a cocktail of enzymes that destroys the microbes including anthrax so it doesn't have any effect on humans but what about the bacteria that lives in our body well we haven't eaten it yet what we're hoping to do is to do a clinical trial soon on removing biofilms so in the wounds of patients the problem that they the reason they don't heal very well especially these diabetic chronic wounds that by the way that every 10 minutes someone's losing a limb thanks to that these biofilms you have to digest them off and you know how they do it right now they scrub them off it's horrific then they cut the skin and they keep

92:16cutting and they cutting and eventually you lose a limb this looks really promising in animal studies that we should be able to not just kill the bacteria in the wound which is a problem but get rid of that biofilm that's amazing so things like Mercer staph infections exactly so able to stop it in its tracks before it gets systemic right spray this stuff on a cruise line for for the virus norovirus even if it turns out to be that safe why not just wipe down schools oh because I always worry about the the negative aspect like what's gonna happen like what's what's gonna be the blowback right like antibiotics is with created medicine resistant antibiotic staph infections right right right your mind always jumps to the worst possible it's me bro blow it we'd make a good good team so I'm the I got a buddy cop movie yeah let's do it so we've tested does it induce

93:20antibiotic resistance and so far it's negative mmm okay interesting oh another thing I'll tell you so I work with a company that detects organisms so we want to detect if there's another virus coming across the planet so how do you do that quickly and how do you do it if you don't know what you're looking for so we can take a drop of blood or a swab off the table and we can see all the organisms that are there we can do your microbiome but that's easy we can do a so drop a blood will tell you all the bacteria and viruses in there and it'll tell you how to kill it which is great for healthcare because right now microbiology labs I've worked in one I used to swab urine and poop on plates it was very glamorous that's how it's still done that is that's 19th century early 20th century technology crawl on a plate wait a few days see what grows but that's useless for diseases like viruses

94:15and Lyme disease Lyme disease you know the one from ticks in you in your spine my daughter got Lyme disease and she was really sick she was losing her eyesight it was serious it got into her brain and the hospital wouldn't give her that antibiotic because they the tests weren't quick enough and they wouldn't give her the antibiotic until the tests were positive for insurance reasons and I said just give me that give me the DNA of my daughter a spinal fluid I'll test it they wouldn't do that so I was furious so I spun out a company out of my lab with some very smart Pi informaticians mathematicians software engineers we built supercomputers to be able to do this teamed up with a guy in Stanford my friend I mentioned him Carlos Bustamante he's the guy that did oh maybe I shouldn't but he did a famous person's genome recently he's been trained on mummies and he did Kennewick Man and

95:10so this technology can be teamed up with what I've done to be able to get rid of all the human DNA out of blood sample leave the viruses leave the bacteria and then run that through us a computer supercomputer all the DNA and tell you within probably seconds eventually what it is so my daughter would would have a diagnosis within eventually will be just ten minutes instead of waiting a week Wow Lyme disease is terrifying there are there are so many people that are infected with it and I know personally maybe ten people that have it and a couple that have had significant issues with it that have lasted for years I know a guy who was hospitalized for a full year on it it's really bad and it and it can hide as well that's the problem yeah and it wrecks joints and a lot of countries actually deny that they have lung disease Australia's a good example people are getting what seems to

96:05be Lyme disease and no one knows if it is or not give those samples to us we'll tell you what's in there well it seems to be very difficult with certain doctors for them to tell if they don't see that bull's eye infection exactly so my daughter our daughter Natalie a middle daughter she didn't have a bull's-eye she had nothing the first things we Bulls are also it's a inflammation around the bite of the ticket right and there's a there's the actual bite and then there's a circle on the outside of it for whatever reason this occurs with Lyme disease but oftentimes goes away quickly so if you bring a person in and they have the Lyme disease but they don't have that bullseye anymore which is what happened to my friend Steve's son he tried to tell them that it was Lyme disease they the doctors were incredulous they didn't believe him it took till the kid had

96:54Bell's palsy at his face exactly that's what happened now family it's crazy and so I was bitten by a tick last year right behind the knee and it didn't form a bull's-eye maybe I didn't give it time but it definitely was a very painful thing I could tell that there was something going on it was really itchy and I went to the pharmacy and I said can I have the antibiotic it's you know it's probably cost a few dollars for the antibiotic and they said no we won't give it to you till we see a bull's and you need to bring the ticket while I didn't bring the tick with me so again I'm the doctors and nurses worst nightmare I wouldn't leave until they gave me the antibiotic and I'm glad because I don't want to wave the wave like give it to you they did I wasn't gonna leave until I got it but I don't want to wait a week you know I'm starting to lose my did you get that

97:42with them you say listen you dumb I'm super smart I work with jeans no not that occasion it's temper that's anything but I know you can always say hey I'm looking for I start Harvard and then they probably just really kick you out yeah what do you say I mean how long did it take before they listened to you so I went through it I basically I started spouting biology so that they knew that I knew something about it oh it was about 15 minutes oh that's not bad they're not you knew what to say I can't be there for days bye bro trust me right let me draw you a picture they take yeah I mean I would just think they'd want to hand that stuff out quick with so many people getting it it's so common I mean we looked at a map recently on the podcast of Lyme disease infections across the East Coast and the East Coast the United States obviously that's where you live is just a hotbed it's crazy

98:37it's everywhere well it is and I've got friends on Cape Cod where it's really prevalent really bad so bad that so they keep the antibiotic in their kitchen drawer Jesus and if you catch a quick enough does it stop it in his tracks yeah so the real problem is when it gets into your bloodstream and you don't treat it long enough or quick off exactly and so my daughter needed it what's called a PICC line which has delivery the antibiotic just straight into the heart Oh cuz they left it too long I'd want to kill them and she didn't have a ring of ring of inflammation but you knew I didn't I thought it was meningitidis bacteria in the brain or something oh holy leukemia was the other possibility those dirty bugs what can be done to somehow another eradicate those things Oh so again why not one of my friends got a few friends here she was working at MIT and she's developed a way using the

99:35CRISPR system to kill these as you say damn little and so there is possibly going to be the first test of releasing a modified organism the lime organism to kill them off Wow and you know that's gonna cause some new superbugs it's gonna kill everybody it's gonna be like that a Brad Pitt movie the zombie one World War Z my pee but on the other hand we might all be saved from Lyme disease yeah we I would like that that would be great I just I mean where did Lyme disease come from there was some conspiracy theory website that was thinking that Lyme disease was some sort of a some sort of a biological weapon that's probably I'm sure but it came out it was in Lyme Connecticut right it does it wasn't that one of the first cases yeah so that's close enough to Harvard just stayed away it's I thought he said Russians were behind it oh no I said conspiracy theory I didn't

100:34say it was Russian but as a biological weapon it's uh it's just an awful thing and that and now there's the I'm sure you're aware of the Lone Star tick that gives people that alpha-gal the disease the one that makes you allergic to red meat mm-hmm just I mean where was that before it's crazy to see these things morphing and well they're morphing and there are a lot of bugs we don't know somebody just published a few days ago that they took surveys of the microbiome on the skin mouth got across the planet different races different foods Geographic geography and they have a hundred thousand different organisms living on humanity and most of them are unknown that's crazy right right and all they have to do is just morph a little bit one way or the other way and all of a sudden people are dropping like flies yeah and what's interesting is on the skin and in the gut of people in India

101:29is very different than what we have and it different smells yeah they probably think we smell that but I know this because well they're wrong yeah right yeah I smell like Old Spice but these wounds they're actually if you want to kill bacteria in a wound they're different in the wounds of people in India than they are over here oh wow that's interesting and obviously they have different diets too so there's probably different things they're used to consuming and so their gut bacteria is different right everything's different that genomes are different so we need to map the globe to first know what we're dealing with before we can address them it just seems like a never-ending struggle it every day is a struggle against the natural world they want to kill us and he is yeah everything the little things and the big things all of it Wow their food so how much of your time

102:25gets consumed with this kind of work uh well it's so everything's all consuming my typical day is at a going to a company meeting going to US government game called by Senator for an update so probably actually let me be formal about this Harvard University allows me to spend twenty percent of my time outside of the university so it's nineteen point nine hmm you have to cover your ass here is that we just did maybe but he tracks their time now anymore but I would think that with a guy like you who's so you concentrate so much you're so focused on anti anti anti aging that having a gigantic workload would seem to me to be that would be an issue in terms of like over taxing your system stressing yourself out so nobody's ever asked me that and it's a really good question but I'm not really worried about dying actually I'm not worried at all at all I know is you know it was a wolf in the

103:33room he's staring at ya you know where a grisly death I'd probably not want that but I've been I thought I was gonna die on aeroplanes before and I'm pretty calm about that so I guess that's a good test but I do want to leave a legacy I want to be able to say the world's better for me being on the planet and so that's why I do all this stuff though I try to protect the humanity I try to protect nature I'm trying to help with food production my aging stuff is what I'm known for but I do a lot of this other stuff that people don't know that so you your concern is anti-aging you certainly want people to live longer but you yourself are more concerned with your work than you are with your own personal life Oh hundred percent my wife will tell you that the reason that I look after myself as best I can when I've got the energy is it would be a bad look if

104:30I'd died from heart disease tomorrow yes the anti-aging guy well if you died from anything other than an accident right yeah all right so I'm trying to be a role model for others but you know if I if I died tomorrow that'd be fine with me I'd like to finish my work at least I would like to leave something behind but what I don't want to do is to be a burden on my kids and my grandkids yeah and so that's what I'm also trying to prevent yeah that would seem to me to be the real final frontier of anti-aging is folks that are really really old because it seems like they would be open to try almost anything and if you could bring them back that would be Boober bazaar right well our way do you think we are from doing something like that well it often comes as a shock to people who don't work on this that we're already testing these molecules in clinical trials on elderly people I've been doing

105:29that for a number of years now with some positive results over at Harvard we were giving nmn and an another molecule called it might be 66 was the other one called my laundry low so that the companies called Metro biotech and it makes super nad boosters and the drug is called developmental drug is MIB - six - six six - six yeah and we're hoping that it will not just have to give that in an alleyway someone ah that I got to go to some shady doctor with a weird accent that one that one we hope to get on the market in about three years from now really yeah for diseases fda-approved and so they're using it right now on folks are testing it for safety but we're also going to be testing later energy we can measure actually the nad levels that molecule I just mentioned we can measure that in their muscles and we'll test if that worked and will will measure of course their endurance

106:33because the mice that we treated with any man they just ran and ran and ran they actually broke the little treadmill in my lab because that ran so far and you're giving it to them orally or you're injecting into them it's a little tablet they just put food put it in their food or something like that all the mice yeah oh no I thought you're talking bout the humans in the mice we put in their drinking water hey let's drink it it's really easy Wow and they have no idea no idea in fact that people who are running the treadmill have no idea which is which but we had mice running three kilometers and then the Machine stopped and I get a text from the the researcher hey the machine broke and I said check the software and turns out software was written to stop it three kilometers because my mouse had run that far before that's long and those are old mice don't forget these

107:20are mice the equivalent of the equivalent of a 65 year old human really yeah and we figured out why they run further this isn't just try it and see we've figured out that that the lining of the blood vessels needs nad as you get older well they need it all the time but as you get older you don't have enough nad so the enemy and replenishes that and allows the blood vessel lining to respond to exercise and even grow blood vessels if you don't exercise and so those mice they ran and ran around they didn't get lactate build-up as much as didn't feel tired so in that lactic acid buildup right Wow so muscle fatigue would be different well they didn't seem to get that either Wow was that just better blood flow we even pinched off an artery and the body responded much better to respect restoring blood flow which would be great for patients who have a heart attack whoa

108:16now with human beings what has been the most dramatic result that's a hard question because a lot of its early stage we developed a molecule that seemed to effectively treat a disease called psoriasis which is the yeah Renee how's that yeah so that that worked and that's a molecule it's something you apply to the skin it was a it was a pill actually hmmm yeah how does that work what is it doing so it's an activator of one of these sirtuins that we found in yeast originally these are too and protective enzymes in the body and they're anti-inflammatory and so it worked well against that disease so psoriasis has something to do with inflammation it is an inflammatory disorder you are all autoimmune disorders and time for inflammatory based disorders I believe so really interesting hmm because I have I have vitiligo you don't see a little spots on my skin where I don't have any pigment its

109:22genetic my grandmother had it my grandmother sister had it I wonder if that would help me uh yeah I really couldn't say what's the call again which one the drug that was tested yeah um it has a name SRT 2104 and this is the stuff that he worked on psoriasis yeah in a small study in New York yeah hmm now what other what other things had really dramatic results on humans well we're not there yet we don't have dramatic results is there anything promising results on humans other than nmn yes there are there so this mTOR i mentioned earlier where the drug rapamycin which is too dangerous to try on normal people that drug has been tried on elderly people and it boosted their immune system in the same way that you see with calorie-restricted mice and so that that was an early signal that you might be able to reverse aspects of Aging in the elderly with that drug

110:20now with older folks one thing you see is the body doesn't produce collagen as much your skin gets lacks and starts to Sag what what things could be done to mitigate that you mean besides Botox itself Oh tox doesn't really do that just freeze your face or well it so I mouse that a lot will it David don't worry about protecting cancer heart disease Alzheimer's I look better can I look better Yeah right and the answer is that a we don't know B we're working on it we have we work with a cosmetic company that so far so good but I don't endorse products that's not me but also what's interesting is that these mice at least they stay younger looking as well they don't just live longer hmm um so this hope that I mean the skin is a big organ okay so right why wouldn't it stay young just like the rest of the body well it's certainly indicative of whether or not a person is healthy right

111:23if you see someone and their skin is really saggy and up looking you assume a person's not healthy right and actually a lot of us scientists believe that how you look is actually a pretty good indicator of your biological age speaking biological age there's a being a breakthrough the last few years being able to tell your biological age one parts done by insight tracker looking at blood biomarkers but there's a new one called the DNA clock I've heard about this yes I have so a colleague of mine is well known for its d4f and what it is is so you know how DNA I said is changing over time and the epigenome is changing so these are like scratches on the clock on the DVD we think we know what those scratches are and how to remove them and what they are little chemicals that bind to the DNA called methyls and the older you get the more mentals you're you accumulate on your

112:19DNA and we can read that with the machine and we can very precisely say you're roughly this age but you're actually older or younger for your chronological age hmm and and now we think we can reverse that Wow how long do you think you are away from doing that being able to reverse there well that's that glaucoma treatment that we're looking at I would like to see you take someone like a a wealthy Mel Gibson type character and just shoot them up with everything like just get someone who's willing to give you a full run of them and run it like out like some sort of a science fiction movie tell you what I'll do it if you'll employ me because I'll be kicked out of my job I'm sure you would but man I mean it just seems like there's so many promising things it would be really fascinating if you could document you could take one person it was like a wealthy man is mid to late 60s well that

113:21there's this orange element in anti-aging in fact I don't even like the term anti-aging it's what do you like longevity research we're about to announce maybe this is a sneak preview for everybody an academy for aging research of the the top I think 20 scientists in the world of banding together to to produce white papers and opinions but yeah we call it longevity research and so anti-aging is is more that the Botox and that kind of stuff that we don't want anything to do right but that's nonsense it's not really anti-aging you're not doing anything about aging you're just freezing your skin so it doesn't move that is that to me is one of the weirder things especially with men when I see a man as forehead doesn't move I want to smack him in the mouth like what's wrong with you sir how dare you respect it just it's not it's a it's not like Botox or fillers or any of those things you're

114:19not doing anything for your health or your actual real vitality you're just weirdly doing something cosmetic right yes you are and though I think the defense is you feel better if you look better mmm psychologically it might help I don't think they look better though they just look different yeah what's the problem it is true yeah I don't spend a lot of time thinking about the cosmetic industry for obvious reasons I'm trying to save humanity and and improve the planet actually I do think we would be judged as a as a species if an alien came down and they said you're shootin botulism in your face right right exactly you are a weird you're not allowed in the club of advanced species well well that would only be one thing that we were from yeah you know but what would they ask you they well they'd ask us have you figured out the speed of light did ask me why I have drawings all over my arm

115:15no no they might appreciate art maybe but like they'd be like why didn't you just get it and then wash it off or something why have to get it drilled in your skin - well not that's coming but I think what are that one of the most important questions they'd asked to tell if we are an advanced nation or advanced species is have you figured out aging yet mmm right deterioration yeah and you know what we're so pathetic as a species our answer would be you mean that's a thing you can do something about that and they're like come back in a thousand years well I mean there's gotta be you think worldwide are working in your field sometimes of leading labs there's about twenty thirty broadly there's a probably a few hundred labs and are they all in essentially the same field of study they're all working with the same molecules and the same parameters know that not everyone works with molecules

116:12but what I can tell you is we get together in conferences and we talk about discovering new gene that extends lifespan and a new molecule that's working in mice or sometimes in humans but it's a big field now it's growing and when I started it was the backward of biology antioxidants etc mmm I was very lucky to start when it was really small and stick it out those fair amount of criticism in those days what how so like that it was like a lot of my friends my supervisor said I was insane for working on Aging that's not a thing that's not biology really yeah Wow wait how long ago was this so I came to the u.s. from Sydney in 1995 went to MIT and the scientists in the lab that I joined Lenny gurantees lab they two students had just started working to figure out why yeast get old and I joined as the third senior person to join and all the other people in in the lab there are

117:07about 18 19 people they said you are nuts Lenny's lost his mind he's working on Aging that's not a thing you should be working on what we do which is understanding how genes are regulated so I called up my mom and I said I think I've made a big mistake here this was the thing and the guy and everyone here says he's nuts meanwhile you were right well you got to take some risks in life that's one lesson yeah but that's an interesting one right because you were a young fellow he didn't really totally know it was pretty lucky because I'm in Australia right I don't know what people are saying about this lab Sheila right there but always been fascinated with aging since I was four well now though with all the promising new discoveries I mean they have to be eating crow as it were talk to those people like oh hey I was right no you know call them up in the middle

118:03of the night drunk no I definitely forgive people too much had some pretty big enemies along the way that I try to be nice is it because research and this sort of scientific work is so competitive yeah it is it is and there's this belief that someone's success is your failure it's not really that that is the case but you don't exist in show business - it's a weird sort of mindset it's a very limiting mindset right and also and this may be true in Hollywood in science if you come up with a new idea and you're young you're a young turk and you're upsetting the status quo no no the Thomas Kuhns book on structure of scientific revolutions was just had it had it right he wrote in the 60s about chemistry and physics but it applies to biology that if you can't with a new theory that's that disruptive the current leaders will attack you and a myriad of chaos and you just have to

118:56get through it and fortune out read kroons book and I knew that this was normal but a lot of people around me were saying oh no people are saying we're wrong and it's controversial we don't want to be controversial I'm like controversy is great that's let's do more of that and if it's not controversial I want to do it that is interesting do you think that's because the people who are the old guard are upset they didn't fight it themselves or they upset that your new findings will make their work look irrelevant yes it's probably better both but mostly it's it's that they're worried that their lives will be have have been in vain if what you're working on is not true right yeah there's a this is an amazing documentary on the Sphinx where these geologists are talking about some of the water erosion outside the area the Sphinx and they're saying this points to the fact that

119:45construction was thousands of years older than they thought and you see this one Egyptologists freaking out he's freaked out like what evidence what evidence of this culture you're talking about like because it apparently it would have predated the known dates of 2500 BC would have made it like 7000 years older than that because it would have to be back when there was rainfall in the Nile Valley and you could see this guy's ego kicking in because he had it was a professor he had been teaching Egyptology and he was freaking out instead of examining this evidence like wow like talking to this geologist who studies rocks and erosion who's really steadfast is a Boston University geologist dr. Robert Schoch and you know he's saying this is evidence of water erosion and he's like showing it and he even showed it to a bunch of other geologists and they all agreed and this

120:36guy this Egyptologist and this documentary was freaking out was like wow that's what happens when you think your whole life's work is horseshit yeah it can be a blow to the ego I haven't lived through that yet it's probably coming but what I've noticed is that the really successful scientists and people in life just embrace change and you know kind of have to I mean it doesn't mean that that guy is a loser it just means he was acting on incorrect information based on what they knew before I mean should embrace it and say look well we know certain things were built at 2500 BC like the Great Pyramid that's been pretty clearly established but it looks like there were some ancient structures that were there even before then let's now we have new things to study they don't look at it that way though yeah see the problem with with how biology and actually most facts are taught or

121:24theories are taught is that there's a textbook and that's the Bible : what I try to teach my students is can you please just forget everything you just learnt and what's important to know is that most things we think we know are not correct they're going to change over time all theories change Newton was wrong but he helped us get here expect that we only know you know 0.01 percent of of what we need to figure out and a lot of what we think we know is wrong anyway so even if you have the greatest theory expect that it will be overturned but you can at least cherish the fact that you've helped us get to that point because without Newton we wouldn't have gone in physics well for someone like me hearing you say that it's very promising and it's it's it's very encouraging but I always thought that scientists were always going on just data like the all they cared about

122:19was data all they cared about is what is correct and that was what was crucial that's what's important this is what they talk about this is what they study when I found out that scientist would would ignore information or use their own personal biases against information or attack research because it somehow negates what they've done is very disheartening for someone who's not a scientist you go oh no the egos in science too right it's just hardening as a scientist I can tell you there was a time of great change in the aging field where we discovered genes control aging and molecules like resveratrol could extend health and lifespan it was it was brutal you I'd get up and I'd give a speech and someone to say you're wrong this is crap and where are they now do you call them up in the middle of night they still home up you've done wrong right I have a couple of glass

123:12of wine yeah well I think the secret to success in life is actually just existing for long enough and all your enemies to fall away yeah well they die they're not into anti-aging yeah I look like I can't walk anymore just have to outlive your enemies yeah it's an easy way that must have been a tough time though for you as a young man and you know you're hearing this from these established scientists and part of you must have been like thinking like geez are they right sure you have to entertain a possibility that you're wrong that that's what we do but you go back to lab and you retest it so I went through a really brutal period in my career where we had data we interpreted it we published it in the top journals and it was about how resveratrol works on that sort to an enzyme that I mentioned and Pfizer came out with a paper that said it's all wrong and I had people call me up saying it

124:07was nice knowing you I'm really sad for you but it's over yeah bad boohead luck and so I went back to the lab we had some data already from years before which I knew were interesting and it took another thing four years to get to the bottom of it but it turns out in the end I was right but there were days when I said screw Humanity Academy bothered getting out of bed if this is how I'm going to be treated for trying to devote my life to the betterment of people's lives it's tough now I think anybody who's at in a position in their career like that has to have gone through really hard times it's just discouraging from a non scientist who relies on people like you but someone like me who relies on the folks like you out there doing the hard work that you would face that sort of I mean I guess the best way to describe it would be ignorant well it it's okay for

125:02scientists to challenge a theory that's what I didn't what everybody is trained to do but to do it in such a public end and vish controversial it was vicious it was definitely vicious even the words they used or vicious which is really hurtful but but they're wrong well they might have been right I could be wrong they call them up middle a night you dumb yeah the person who published that paper I do think about meeting that person again but they do enjoyed careers it's not just it's tough you can run out of money your students go well sure that was happening to my lab we went down to four people I mean and what was the higher I mean these days I'm but what were not before then it was about 18 20 and you went down the 4 4 so it was looking bad oh yeah people had written me off holy but you were right when you got to push forward it's uh you got to get lean

125:57because you're not gonna get government funding for a while because people think that you you're a failure god damn that's crazy well sciences is not for the faint of heart I would imagine yeah yeah boy they skin stubbornness only only those survived what was the turnaround like was there a moment where it turned around and moved in waters favor yeah there was there was one day when it when it all changed so the earlier data so what data driven the early data was that the enzyme we could we could mutate or change the enzyme so that it wasn't going to be activated by research role and we found that mutation now that just technically or non technically technically means that we could change the enzyme in a way that wouldn't work so we then put that non working enzyme into a cell and now we have a mouse that doesn't work and we give it resveratrol and if it if it works

126:57it means I'm wrong if it doesn't work and it's blocked by that change in the enzyme we're probably right and that's what we did but the real the real change was that there was a company that I started that was making drugs the one that cured or at least seemed to cure psoriasis and they had made these very synthetic molecules that were not related to the plant molecule research well and so I said to myself and to the student who was working on it a very brave student if if the change in that enzyme also blocks the drug then we're on to something because that means two separate groups working on separate types of molecules different people different systems all get blocked by this one little change in the enzyme then we're right and and so he walked over to the company he got the molecule through it on the enzyme and it didn't work on the mutant and that was

127:53me rejoicing because I could say there is a universal activation mechanism on this one enzyme resveratrol works the molecules at the company work and now there's an interesting thing that just came out from Spain that metformin the diabetes drug may actually work the same way as these other molecules by activating our favorite enzyme the sirtuin Wow and how how much time were you in the Darklands it was a couple of years of hell right it gets so bad because you've got this tight-knit group of scientists and you have lab meetings and you present your results and usually you're very supportive trying to help I had one guy saying to my student David doesn't always talking about you shouldn't work on this it's been proven wrong he was dead against me in my own lab I'm paying his salary and it's okay to be constructive but vicious within my own group well suffice to say he wasn't in

128:50my group for that long Wow now this other guy that used all these other vicious words about you where's he at now not sure I would know I wouldn't know no I don't have time to look back community forward you're nicer than me yeah you know what um in science because it's very collaborative and you're often your enemies are reviewing your own mmm work if you build up too many enemies you want survives no it's definitely healthier approach I'm kidding I probably would do exactly what you did but it stills got to be beautiful to come out on the other end and be proven correct and actually be at the forefront of these emerging technologies uh well it is I don't rest on any laurels but the what I do is I pause and I remember how hard it was to get here and how fortunate I am to have made it this far and I'm working with hundreds of collaborators around the world to make

129:46this come true this idea that we can really treat aging and prevent deterioration so I'm blessed I have an app on my phone that I've helped engineer what's that it's called Lua Lu a and where's that well it's a little company that we bought in New York and nurses and dentists use it to pass medical information around but we use it to share information between scientists around the world and coordinate activities between companies that I've started yeah so there I you know I think I mentioned to you that I've started a few companies what I'm trying to build our companies that are the 21st century version of a pharma company is actually has a decent reputation in the world I think it's pharmaceutical companies whether it's deserved or not have a pretty bad rap I'm trying not to fall into that trap but I'm also trying to use 21st century technology to not

130:44become too bureaucratic as well within the organization and that's what the Lua app offers us you were also talking I don't know if you talked about this before the podcast about how you have to make sure you have zero conflicts of interest yeah it's hard so I don't I don't sell any supplements I don't endorse anything no products but if you look on the internet you google David Sinclair and nad or aging you'll see that people put my name and my face all the time on their websites and I get questions every day every morning I wake up which product are you endorsing mmm and so I'd be extremely careful so do you have to have a lawyer contact those companies tell them to take your name mmm yeah yeah it's a fair amount of money always sending out cease and desist letters but I have to do it my reputation is everything and I also want to be able to have opinions on these molecules without

131:37someone accusing me of doing it for a profit that's what I would think would be critical point to that and say hey he endorses this because he's making money yeah yeah that's what would be yeah that would be the thing that I mean especially because most people aren't going to do real research and developed a nuanced understanding of your work and what you're doing what it means and how long you've been studying it they go oh he's doing it because he's making money I'm done you know right well you know I've made a fair amount of money in my life my first company even though it wasn't the major shareholder was sold first north of 720 million dollars so that money I'm not immune to but I do reinvest almost all of it actually all of it my wife will tell you into new ventures to change the world so though the Lyme disease company and the miv 66 company Metro these are

132:28funded initially by me now the conflict arises because I'm studying these molecules in the lab and I'm on the board of directors and advising these companies as chairman vice chairman the only way around that as a scientist that we that we have is our defense as we disclose everything so initially I would disclose it to the government and to Harvard all scientists have to do that but I've gone a step further just to try and be ultra transparent with the public and so I have a website if you go to my labs website you'll see everything that I do and and hopefully that's a protection from being accused of being biased but what I I definitely do in my lab is I say to the students if you get a whiff that I'm doing anything biased I would I wouldn't do anything consciously but maybe there's some unconscious bias let me know let the University know and we'll be fine but I've been doing this

133:20for 25 years I think I'm pretty good at putting a a wall between the two and the other thing that I want everybody knows in a lab we do very basic research we try to understand the fundamental reasons why we age and how to reverse it the companies are more worried about how we get into a clinical trial which is very different worlds so they don't have a lot much now when you want to bring something to try something to the market or you want to try something on people what's the process let's say if you have some sort of a molecule that you want to try out on people what is that process so it's a few years of often making a better molecule but let's say you've done that work now you you spend a year testing it on at least two different species usually a rodent a mouse and a dog and but you try to do everything you can before that to make sure it's not

134:15going to be unsafe testing our own cells and other things that are not living or at least not not don't feel anything but the FDA Food and Drug Administration of the u.s. requires if you can make a drug you have to test it on at least two different species so that's what you do and then it's you're going to what's called phase one which is safety testing takes one to two years Phase two is what we call efficacy which is does it really work potentially so you test that on 50 to 100 people maybe it works maybe it doesn't most things fail if it looks good then you go into Phase three which is 50 to 200 million dollars worth of experiments I'm testing it on hundreds of patients and if that goes well then you apply to the FDA to be licensed at the seller drug so the amount of money that it must cost to bring something to of my ears open you're like oh it's it's hard

135:08must be staggering it's it's staggering to raise that much money and that that's one of the reasons that these big numbers come up often we have to tap the public markets to be able to afford it a typical drug will cost in hundreds of millions of dollars some drugs have failed after 700 million dollars investment oh yeah but but look at the upside if we're successful at having a drug that treats aging you know we'll treat a disease like diabetes first but then it could become the best-selling drug of all time if it's proven safe who wouldn't want to have a drug that could protect them from all these major diseases yeah but how much would something like you'd have to sell it for so much money to make up for all the research money right is that how it works that's how it usually works but for the first time I'm in control of many of these companies and I have a

136:04large say in them at least and I as an individual and pledging that we won't do that we're not going to put prices up to what the market can bear we want this is a gift to the world and so that's a very different approach and that's one of the reasons that I've in large part use my own money to do these things so I can have that say and do what's right for the planet so when you do do that how will you decide how much something costs based on the ability to just maintain the company well yeah we have to be profitable otherwise it'll it all goes away right but not to the point of extortion know there's that there's a nice middle ground what right you don't want to be like that guy that went to jail for the AIDS drug what's that name you know that kid you know Oh squirrely yeah that kinds Carly you know I have a very different view and I'm hoping that we'll have a new type of

136:57pharmaceutical company emerging out of what we're doing that's amazing right because pharmaceutical drug companies are always thought as being a devil meanwhile they're responsible for so many things to keep people alive as well but because the fact that connected to things like oxycontin and fentanyl and things that kill people and it's been proven that there are certain unscrupulous drug companies that have pushed things out there that they know have negative effects because they knew they get profit from it right well that not everybody is it ethical but as long as I have a say in these companies that will be ultra ethical you got to make sure that you stay alive they're gonna try to take you out bro well yeah I don't know about that but you out take control the company I founded the profits I found like-minded investors for the first time that's amazing - I

137:45mean how how have you managed to cultivate that relationships it's it's harder than going with a pitch to a capitalist but it's mainly meeting the right people I want to see that they're on board - I don't want to just have somebody who's out to make a profit right but you still can make a profit still be profitable but don't go crazy right right and help the world yeah and so we just recruited to one of the boards of the company someone from a consumer company which is a strange choice right but this is a person who's done right at that company for the world a company that used to make just some consumer products that weren't healthy and he turned that around and that's the kind of person I want to work with who cares about the planet more than they care about the ultimate profit that's awesome man listen keep me keep me in the loop I want to know what's going on

138:40and I'm gonna try all these things you said so I'm gonna go out I'm gonna buy some nmn I'm gonna buy some resveratrol I got to find a quack that's willing to prescribe me metformin I've got you know we'll talk later and then the other stuff the SRT 2104 that stuff where would one get that that's experimental that's probably hottest one and to help you with you need to pay somebody off um anything else I need to know about that it have you had you know are done just 23andme basically you know I haven't is there more extensive versions of it than that there are in there a few thousand bucks do you whole genome and we could do that but I don't think you'll learn a lot more mainly because we're ignorant as to what the other stuffs doing right it was pretty interesting though you know as far as finding out about my ancestry and where my relatives come from yeah it's a

139:39good start I learned some really interesting things too about my origins and I'm carrying Cystic Fibrosis tea and whatever Wow but what's cool is now we're merging you can merge that data with the inside tracker data and have this ultimate you know personal angel for health that will hopefully one day be on all of us that we've got the personal tracking device it'll tell us if there's something going wrong if you are a cancer cell detected go get that eliminated it's crazy these days we have to wait till there's and actually a tumor that's making you sick before you usually go to the doctor an actual issue well now I know why you're so excited about the future so you you have an inside track on this yea front row seat and I'm glad to share a little bit with your listeners oh thank you I really really appreciate it tell the listeners and the viewers what your website is oh I just

140:30have a Harvard website but I will be I'll tweet about this I'm launching a website for a book that I plan that I'm writing now it's gonna come out later this year we hope when it comes out come on back we'd love to all right update thank you David really really appreciate it that's it bye everybody