Unknown

hello everyone our program is about to begin please take your seats and silence your cell phones we have a full house tonight so if there is an open seat next to you please fill in and move to the Center thank you e good evening hello everyone my name is Jenna Mo I am the senior director of The Society of fellas here at the Aspen Institute and it's wonderful to see another Full House and smiling faces thank you all for joining us I know that Aspen is rich in cultural opportunities and it's an honor that you've

chosen to spend the evening with us so thank you for being here also happy summer I know it's a little warm today we've got the doors open for Breeze and um AC mechanics on their way so if you get a little toasty uh we're aware and we're working on it so thank you I'd like to acknowledge my colleague Crystal Logan vice president of the Aspen Institute and director of Aspen Community programs we present the summer series together and it's a delight to have her leadership and expertise in curating the summer speaker series and to work

with the the various teams of the Institute so thank you to Crystal you're it's also important to acknowledge Gina and Jerry Murdoch um for their leadership and their generosity and underwriting the Murdoch mind body and spirit series thank you to Gina and to Jerry with their generosity tonight we are presenting lifespan why we age and why we don't have to and I'd also like to acknowledge the members of the Society of fellows who are here in the audience tonight with their generous contributions to the Institute we are able to make evenings to like tonight free

and open to the public and members of the Society of fellows go deep with the work and the impact of the Institute to drive change through leadership and dialogue so thank you for your annual support it means a lot to all of us and if you're not a member please join us it's now my pleasure to introduce our featured guests our moderator tonight is John Driscoll who's a dear friend Society of fellows member and also senior adviser at Walgreens boots Alliance and of course our guest of honor Dr David Sinclair officer of the order of

Australia tenur Professor Department of genetics at the Paul F Glenn Center for biology of Aging research Harvard Medical School he's also featured in seven books three documentaries on 60 Minutes and in many other important media so please gentlemen the stage is yours and thank you thank you John David I'm a little nervous I've never interviewed a KN before yeah um you know David is also the as as I think everyone here knows the leading researcher on longevity and aging and has provoked uh perhaps the most creative and successful entrepreneur of Our Generation Lon musk uh

has uh on on X communicated David that our lifespan is programmed by our genes what says the night uh well you know I don't Proclaim to be uh an aerospace engineer but I do know a little bit about biology and uh and what's surprising is that uh only 10% of our future health is determined by our genes and that's surprising right we're told DNA is our destiny and at most it's 20% but it's certainly not the majority so I you know I'll I'll debate Elon on that any day and and how did you get come

to this area of uh you know sort of making America young again I mean making the world young again like sorry just had to neatly at that in there what what how did you come to this field uh well the first thing is uh I came to the US um it was it was always a dream of mine I grew up in Sydney Australia as I think most of you know hence my accent but I I came to the US because it it especially Boston it's this world center for biotechnology and Discovery you were there

you you were in a lab that discovered how DNA separates in the cell and copies itself it's really it's an amazing place to be at harv in Boston every day I'm uh I'm grateful to be there uh and I sought out Boston as a place to go to because it's the mecca uh I think if I was born in in ancient Greece times I would end up in Athens I'm just attracted to where the action is happening and Sydney though it's a beautiful place to live it's not really the place of action for for World

change and I I not only do I want to make Americans live longer um it's now my home it's my country um but my hope is that for many generations perhaps indefinitely as long as civilization exists that the research that we're doing will will benefit the entire planet both rich and poor countries old and young people and is it really true that Robin Williams was your inspiration at age 20 could you maybe explain that which is doesn't show up on your scientific background it is true uh it was a turning point what I what I

what made a big difference to me was seeing the movie Dead Poet Society and you might remember uh and those of you who are watching uh and have not seen the movie there's a scene where Robin Williams he's a a teacher at a at a school and he's showing the boys at it's a it's a private school for boys he's showing them these old photos of the teammates from about a 100 years ago and he says everyone in these photos is pushing up Liles or daisies uh and he says you know what you will be

too you will be dead one day mark my words and what matters is every day Make Every Day Count carpium carpedm um and he whispers it like a ghost from the past and it gave me shivers at the time it's giving me shivers right now and to me that really hit home because no one had ever voiced in a movie uh let alone my life what I believe in which is that Humanity can do better and that we need to make everyday count and we we need to fight against the entropy and the bad people

in the world uh my grandmother taught me this she said David you need to make the world a better place than it was in the 20th century she grew up post World War II she lived through uh really uh she was she was a saving Jews in in Hungary and she saw the worst of humanity then came in the Russians into Hungary and and raped a lot of women and shot a lot of people and she lived through that then she escaped to Australia uh at gunpoint and uh and raised essentially raised me cuz my

mother was working as a biochemist and she told me uh that I should make the best of my life and sees every day and I've lived that way and Robin Williams just made it legitimate so I I want to I want to start at the end and we'll go back to the beginning uh what's the opportunity to extend aging you're you're you you you put some numbers out there in terms of lifespan as well as health span do you want to throw a number out there and tell us how what the what the opportunities of

current Investments could mean in terms of how long people could live well here's one thing I know um that there is no biological law that says we must die right there is nothing that says we can't live as long as a whale whales are very similar to us genetically they have one blood they're conscious they have babies they have milk this they're basically very large very large they're very large they can live 200 plus years and our DNA is not that different so what is it that allows a well to live 200 years and us

to live on average 80 years there's something special and it's not just in the genes there's something else that we think we've found that makes a big difference and so I don't like to put numbers on it because I think that it's like asking someone 300 years ago what's the fastest humans can go and they probably say a horse would be the fastest a human could go uh but we now know you know that there really is no limit except the close to the speed of light for humans I think the same is for aging

we're at a turning point in medical history where we finally understand what's driving aging and in large part how to slow it down and we're getting insights into even how to reverse that process can you can you you you've you put a really interesting Theory out there that's played out in the lab called the information Theory of Aging Maybe we could go a little deeper on that and sort of the what you what what goes wrong in epigenetics and then what could go right yeah the information Theory of Aging is a a new way to

think about what makes us human what makes animals tick and why do we get old just basically to explain it to you all it's the idea that aging isn't just wear and tear right we're not just cars that wear out and break we're living organisms and the we have repair systems and we're Guided by uh systems in our cells that have a memory um DNA is a memory of the past right from our parents and there's other types of information in the cell that we don't talk about as much but are more important than DNA

for aging and that's the control systems that control the DNA we call this the The epig genome it's it's structures that that wrap DNA DNA up in loops and other things but to put it simply aging is like corrup a corrupted software program in a computer in in according to my theory and that's a that's a big deal because it's it's not like a car a computer can be reprogrammed it can be rejuvenated restored and you can run new software on on an old phone and it can run like a new one and uh so

we we have really good evidence would never say proof cuz in biology let alone physics you can't say uh proof but we have really good evidence that every cell in our body has the software that gets corrupted leading to aging we can we actually did this to animals uh and show that corrupting their their rapid you know made them age more rapidly um but then we thought if we can break it we can also fix it and so we've developed ways to reboot the software of the cell and there's a memory there's a backup copy

in every cell of earlier information and that's what the information Theory of Aging is about is that we can reboot our software and rejuvenate cells and rejuvenate tissues and we've really seen some remarkable stuff in mice and now in monkeys and hope can you talk a little bit about the mean you I think it's in cell in 19 in 23 that you published in probably the premier uh Journal peer review you it's the top of the the the of the of the scientific order what you showed and what you Pro what I would say based

looking at the the work proved in mice thanks John you're very kind um well so so that paper means a lot to me because it it it was 40 46 people's work right I'm just the representative it was 13 years of hard work it was started at a time when nobody thought that information had anything to do with aging uh certainly not the epome and so there were a lot there was a lot of risk uh and the information Theory of Aging was was barely heard of and there was nobody paying attention to it but

but my team and my collaborators they bet their careers that this was something to work on and 13 years it went so long that we lost three of our scientists along the way two to co and one from old age uh but still it it was a massive effort so I want to give them credit but what they showed and we finally got it accepted uh and I think it took that long because the world wasn't ready for it actually but finally the world was ready for it and what we showed was that when you

corrupt the software the epigenome of a cell of a human cell or even a a whole Mouse the mouse gets older it gets diseases of Aging its brain gets older its kidneys its skin gets gray hair we can even measure the biological clock in many different ways and this mouse that we treated hundreds of mice that we treated they were older by about 50% um and of course you know our goal is not to make mice get older of course that's not really what the what our our main purpose was it was to show or

test the theory if we were right we would see aging if we were wrong we'd not get aging we' get probably a dead mouse um but we got aging and so that was the first evidence and the title of that paper was um evidence that um epigenetic noise is a cause of Aging in mammals um and then to compliment that we had a paper in another Journal called nature where we we actually also top of the Heap in terms of peer review and yeah we we we fight for these papers to get into top journals

um and that one was a big one too because that one showed that you could reinstall the software in an animal and reverse aspects of Aging um and even cure blindness in mice that had either have had damaged eyes or had glaucoma or just became blind blind through old age and I figure if you can cure blindness you can cure a lot of other diseases as well and that's what we're working on currently and and um maybe maybe I'd love you to touch on what epigenetic noise means and maybe I love the example of the

piano and then maybe talk to it then we'll talk about the primate stuff joh I appreciate your questions it's it's obvious that you've you've read my book and which is great uh it's a good book by the way it's uh I you know it's a it's a lot of time to invest but so I appreciate anyone who's read it um the the part of the book that I I think is is really uh important is the not just the biology which is is part of the book but it's also the societal implications of what where

this is actually going and one of the things that that is surprised me just about the book before I get into uh the science of it um is that it it's not just older people that are interested it's it went Global it's it sold a lot of copies and even young people are big fans of it um so where where we're headed uh right now based on how long we're going to live all of us are young oh for sure I believe that actually now when I see someone who's older and my my father's in

perfect health at 85 uh I don't see an old person I just see someone who needs rebooting it's true and and that's true for a mouse and the good news is we can do it in a mouse so I don't think it'll be that long before we can do it in in people and we're we're working on uh clinical trials for next year for the eye and then uh one of the things that that we published last year is that we can do this fairly cheaply and easily in human cells using chemicals instead of gene

therapy and so it's not crazy to think that one day in the same way we used to think artificial intelligence and cars that drive themselves was impossible or for future Generations age reversal seems to be something we in our lifespan will see and hasn't Dr sander kind of shown that with primates and restoring vision and using similar approach uh I'm not aware of primate the the Primate Research where there where they've actually restored uh restored Vision oh using our technology yeah they they have shown that that was um exactly Dr sander um I can help

you with the citations yeah I thought you said s but yeah yeah probably you're right in pronunciation so anyway the the the the point is that it's not just mice now mice have different eyes than us but a monkey's eyes are identical to ours um and so I'm I was super exciting for me just given how frequently we've kind of reversed cancer or slowed down cancer in mice but we've never really reversed aging and that and just the fact that the restoration of vision is extra it was extraordinary what you what you what you done

I thought it was extraordinary cuz uh I remember going home and and uh my family didn't really uh think it was a big deal they told me that they someone in my family said said David you need to unpack the dishwasher and I said Jesus got respect uh that was my joke but um I think curing blindness is it is a big deal because we didn't we didn't choose the eye because it it was going to work we chose it because it was difficult you know similar to JFK going to the Moon you you you

choose to go there because it's it's a challenge um and if it's going to work in the eye I think it's likely to work in other tissues and if you're wondering what do we know now well since that paper in nature we and and many of my colleagues now there are whole conferences on this uh age reversal technology um I was just in Barcelona with uh probably a few hundred scientists doing this um so I know the latest is age reversal in the brain we've done this in my lab and others have done it see

we can uh cure Alzheimer's in or at least reverse large aspects of Alzheimer's in a mouse now uh hopefully reversing the age of the human brain will have the same effect which means that memories will come back ability to learn will come back that's what we're hoping uh we're working we've shown that we can reverse aging in in kidneys and liver and uh what else are we doing um peripheral nerves we're looking at whether we can treat and cure ALS which is something that um Serena my partner has in her family um and so what

this and the skin we've done as well we're looking at reversing hearing loss we've got some early results there so what am I trying to say I'm saying that the eye is is just the beginning I think but I think you're you're slightly understating some of the critiques and push back and the battles that you and other folks in longevity and aging research have had to fight I mean I is aging considered a medical condition worthy of treatment well no not not not the main mainstream medical establishment right you go to med school I teach

at med school um usually the approach and anyone who's been to a physician knows this that uh you know I'll use my doctor as an example because I I don't know specifics but my doctor will say David hi nice to see you after a year nice of you to call call in they are not proactive my doctor doesn't tell me to come in I have to make the initiative I go in and he says how you sleeping good how you eating good how you feeling good okay what do you want me to do come back

when you're sick you know my point is to him I don't want to come back when I'm sick I want you to take care of me so I don't get sick now increasingly there are a lot of doctors who are getting on the band the bandwagon now uh as you probably know longevity is becoming quite fashionable so there were some doctors that were up to speed but most doctors still think that their job is to treat diseases not prevent them and certainly they don't think of Aging as a medical condition like I do um I

I've written in my book I've spoken publicly that if aging is defined as a medical condition and we can choose to call it whatever we want we can call it purple if we want but I think if the FDA in this country or the equivalent agency in another country calls aging a medical condition it's going to be very similar to how we used to view and now view obesity you might recall there was a time not too long ago maybe 15 years ago where obesity was typically oh it's you can't you have no self-control you're

fat cuz you eat too much it's not MediCal it became a medical condition doctors wanted to treat it and now we have some medicines that are amazing a little overused but they are amazing and the same will be I predict for aging the first country to declare aging a medical condition will attract a lot of investment a lot of attention um and I think a lot of other countries will follow suit I'm hoping that the US will be the first but there are a lot of other countries interested Singapore UK Australia just to name a

few how how are we doing as a country in the in that battle to combat to research investigate and combat aging are we a head behind is this something we could pit ourselves against the Chinese and lose uh well there seems to be a global battle on this topic similar to uh AI um the good news is that we as a country are are really far ahead currently most of the world's major papers on Aging research have come from the United States and maybe 20% from Europe so it's we are the center of the universe

for longevity research currently but the rest of the world is catching up particularly China they've invested a lot of money in this billions and the Middle East is investing uh just to take one country Saudi Arabia uh they have pledged a billion dollars a year in longevity research so we may not stay leaders in this if we don't keep investing and actually might be saying well wow the payoff is in the trillions obviously in healthcare we've calculated this we should be investing as a country in this technology well less than 1% a fraction of 1%

is invested in aging research right now uh most of it goes to specific diseases that are caused by aging um but really My Hope Is that we'll put more money into understanding the root cause of these diseases which I believe are all the same heart disease diabetes Alzheimer's all mostly have the root same root cause the mechanism the corruption of the software and the body can no longer cope with the problems of the brain and the kidneys and the liver that's why I think if we reverse the age of tissues like the eye the body

will heal itself and these diseases will just go away like we're resistant to these diseases when we're young so from a public policy perspective if if you wanted to make an investment in the health of America and implicitly the health of the world what should the government be doing oh well yeah it's all about research and it it's been shown uh in nature magazine there was a good article showing that um a scientific article research article that showed that large teams are not the way to go they're not the ones that cause dramatic shifts in

in scientific paradigms it's small teams so often you know think oh let's invest a billion dollars in this company or in this group but actually it's this the teams of five to 15 people that make the big difference of of students and kids who dream um so that's where I would invest if I had a choice i' I'd give a th000 grants across the country to little teams to work on this topic and at least a few of them would come up with Nobel prize winning stuff from a regulatory perspective do you feel like the

FDA is a good partner I mean you know the FDA has come into a lot of uh criticism in the few years but if you but getting away from that it is the historically the premier regulator and supporter of pharmaceutical and healthc care services are they playing a positive role in the in in supporting your work and others uh yes and no so they have and they is a lot of people right so there are individuals at the FDA that I've met and my colleagues in the field have met who are extremely excited about aging

being declared a medical condition as far back as s years ago uh they those individuals at the FDA said if you can prove to us that aging is treatable then we will very strongly consider aging a medical condition so it's been on us and the medical community and investors to show that and we're working on this there are whole conferences on this topic but it's a little harder to to show this because we don't have well recognized biomarkers of Aging yet there's some decent ones there's some blood tests now that we generally recognize um so

with in the absence of these recognized biomarkers so for cholesterol heart disease that was easy for obesity it's pretty easy get on a scale uh but for aging it's different and so it's it's been a little slow coming up with a way to prove to the FDA that we can treat aging but we're getting there it's also been hard to attract investment because a lot of the drugs that we believe slow aging are already on the market uh not for aging of course uh for other diseases they've rapamycin which is an immunosuppressant but in low

doses is thought to improve longevity at least in animals it does time and time again and it's conventionally used for organ organ transplants like it is it is in regular use in hospitals and every well Raper meon most of it is used off label now by the public for longevity but it was developed for for immunosuppression like you say for organ rejection preventing organ rejection metformin metformin is a good one that's a type two diabetes drug taken by tens of millions around the world it's very cheap and there's some good evidence that it it slows

diseases of aging raging from cancer to heart disease and even fory and so it's being these drugs are being used off label but to get an investor to give money to to you know it's probably going to be 25 plus million dollars to show that it's slowing aging not just associated with slow raging but actually Placebo control trials it's been challenging for those who have tried to do those studies tame is one for met foreman and they've really struggled over the last uh seven years to raise the enough money to do that and it's a

massive study it's like 45 people yeah unfortunately but there is hope there are a lot of drugs in development for other diseases for example you know the eye work that I'm doing I'm also I've started a company 10 years ago that works on NAD boosters probably some of you know what NAD boosters are um there's NN and NR is examples by the way I was shocked to hear that NN one of the molecules that we first worked on in my lab 10 years ago is now a$2 a half billion dollar industry well apparently there's a

lot of people selling it with your likeness that you have nothing to do with I I don't sell I don't sell molecules on the internet and uh which which will shock anyone who googles David Sinclair and a well every couple of weeks uh our attorneys are sending out season to cist letters it's quite expensive but you tell the the the experience of going through the Singapore airport and seeing oh yeah so seren and I were in uh we're in Hong Kong Hong Kong s and uh I I Mose it on into the pharmacy just for

something to do uh and a woman came up to me and showed me a sign it was a big sign with lights and it said NN and uh she had no idea who I was of course and she said let me show you this new thing and Serena and I went up to this two rows of shows of NN uh lots and uh and I picked one up my name's on it picked up another one my name's on it so so the the work he's doing is remarkable but the N you're not really getting fair

treatment on your name and likeness uh well no actually I'm I'm accused of trying to take NN off the supplement Market which is also not true um and the reason is that we're using NN a version of it as a as a drug candidate we're doing doing what I call the the ethical path which is raised many millions of dollars to conduct clinical trials with this molecule uh and that's another company called metrobiotech um but we've got decent results now and by we of course it's not me it's my colleagues at Harvard Shelly bason is

the pi at Harvard who's done this and uh so with nmn if you take a gram or two grams you can raise Ned levels Ned is something that declines with age and it turns on defenses of the body something we first discovered in yeast back when I started my lab 20 25 5 years ago um and so the point is that these clinical trials have shown dramatic dramatic effects in people so far lowering cholesterol bad cholesterol lowering of blood pressure lowering of triglycerides body weight control lowering your body weight and uh some decent evidence of

improved Fitness which is what we see in the mice the mice on anmen run run a long way uh they even broke the treadmill as you know from my book um and so right now we're doing five separate clinical Tri one in a rare disease called FR taxia and the one that's probably most uh interesting is taking really fit men um we should do women of course but just to save money we're doing one seex um and also because it's being funded by the military um US military uh we hope to see gains in blood

flow oxygenation which is we what we saw in mice if it translates to humans um and so I guess one one one way to to end what I'm saying that's important is is there are lots of ways to get a drug that can slow aging onto the market and aging right now is not the way to do it because there is no disease cold aging when you think about all of the work that's being done all around the world but particularly in the labs that are in the US and doing remarkable stuff what's the impact

of the you know sort of order of magnitude increase in compute power and artificial intelligence on the work uh that's a really good question and uh was I I was recently uh following Sam Oldman on stage and that was that was the perfect J jux position um it it's big right but you also have to be aware that there's a there's Global competition but in in our work we use AI I think any biologist perhaps you could say any scientist but certainly in biology if you're not using AI you're going to get left behind because

we can conduct instead of one experiment a day we can do millions in fact You could argue we can do trillions um so we we what we do for example you might say how how does my lab use AI well of course my students using chat GPT all the time um hopefully not to write their thesis but uh what we do now with AI is um one of the challenges of of tackling aging has been how do you quickly test molecules or Gene therapies to slow down aging in in a system that actually represents aging

uh and doing it in mice would be prohibitively expensive of course doing it in humans is even more expensive so what we needed was a way to screen millions of cells of billions of cells actually for young versus old and old being reversed back to Young and we I could show you pictures of cells that look identical we paint them with five different colors and they look beautiful and my students or postdocs they show me these images and I say they looks great and they say one is young one picture is Young and one is

old I cannot tell the difference but we've trained AI to be able to tell the difference and they can tell almost every time whether the cells are young or middle-aged or old or reverted back to Young and now we can screen and we are screening millions of chemicals for ones that reverse aging and that could be one day used as medicines to treat diseases and reverse aging itself um and the other thing we're doing now and this this blows my mind but we can now now thanks to in part Google's work is we can take

every gene in humans or every Gene in a whale or every Gene in in an insect and model take take the one-dimensional information which is the the four letters of DNA and turn that into three-dimensional vibrating proteins in silico right so before a crystallization of a protein was a PhD thesis now in we can do it in a matter of hours for every protein that humans have that's all there then you can take all of the known drugs and all the chemicals that are have been discovered by humans plus theoretical ones and match them up

and say all right we want to turn down this protein and activate this one tell me what would the molecules look like and they do the experiments that would take probably a million years to conduct in the lab they do it overnight now what what intrigued me in in the anecdote in the book is when you talked about how the government at a senior level brought you in and asked for okay what are the four or five things that are going to actually have National Security or impacts on Humanity that science could bring in this

is before AI really hit you want to just talk a little bit about that anecdote to give people a sense of the acceleration wow you you read my in great detail that was a oneliner I think it was almost like I not sure good one liner because he doesn't actually tell you what he says he tells you that there are five important things I told the government but I can't tell you I literally cannot tell you to this day uh i' I've signed a document that says I could be shot if I give away government

secrets as you know um but what I can say is that I I I have uh been asked to give my services to the US government um from everything ranging from biod defense and as you've been uh involved in that uh to Fitness um and uh the Navy Seals um I'll tell you an anecdote in in a in uh in Li of giving you um you know National Secrets the story is that uh I was I was at at the Pentagon and we were talking all about this stuff and and they were very surprised at

at how advanced some of the technology was um and uh I I went on the Joe Rogan show and and Joe said you work with the military and I went that's really not for the public and he tried to get it out of me and again I said not talking about it um but it got me in in some heat and I almost lost my funding for that um but the the irony is that just a few years later uh I guess because the work was now popular the government put out a press release that

said we're working with Sinclair uh so I guess now it's okay to talk about but I think it it but I think what if my recollection is correct you gave them five things that could happen in 10 years and two of them happened in six months that is true that that is true and that is public knowledge and that's that that blew my mind too because it technology is going so fast that even I as an optimist uh underestimate the pace of change and I think that's a that's a cautionary and a reason to focus

on the work that you're doing because I do think that AI will accelerate what we can do in silica which you can only previously do on the bench yeah it will it it blows my mind how how fast we go these days and uh what so my my PhD in Australia it was to clone the genes involved in metabolizing an amino acid called Glycine and it it took me four years to complete that yeast stuff the yeast work I was working in yeast cuz no wonder people didn't in your family didn't take you seriously it

smells really good so I love I like the organism but what what took me four years uh now you can uh do in about 10 seconds yeah yeah that um so everybody David would would love to live better live stronger live longer based on what we know today uh what's your what's the advice that you can give that's not top secret or code word controlled yeah well the I know Robert waldinger from Harvard was here last year some of you probably saw him uh he's got the best um and maybe we I can add to

him because I don't just want to repeat what Robert said Dr Walding I should call him but I I do want to start with that because it it's not that hard to live long my my father doesn't do a lot he's 85 in perfect health he still drives a car without glasses at night better than most people my age I'm 55 now and uh so he's a Beacon of Hope and what he does is with a few little tweaks we can talk about um he doesn't smoke doesn't drink he used to uh but doesn't um

he exercises a few days a week at the gym he walks a lot he walks about 6 miles every few days uh with a friend um he has a great social network that's actually number one have someone you can rely on if you have a spouse or a partner who you can you can whine to and they'll listen that seems to be the most important thing um don't be o overweight um and don't stress those were the the main things that he found by looking at lifespans of people but that's just the minimum and that

gets you 14 years on average of extra life that's and that's the easy 14 years that that's just point let that sink in yeah and and that's the that's easy right what else could we add to that well you know there's there's certainly nutrition and my partner Serena has has educated me a lot on this I've largely given up meat and alcohol because of it and dairy um and my my appearance even improved within a matter of months and also my inflammation in my bloodstream so it's what you eat as well and I used to

think vegetables were for decoration on a plate they aren't and I've I've since learned because Serena's among other things a chef trained at lorum Blue uh she showed me how vegetables can actually be tasty uh it's not just vegetables it's legumes it's hommus it's bagosh all of these great things think Mediterranean diet U I gave up alcohol because we actually now know despite what I was professing 20 years ago that even one glass a day will damage your brain and make the gray matter smaller um unfortunately so it doesn't mean you have to never drink

wine again it's just what I was doing which was a few glasses every night was definitely something Serena allerted me to so I don't do that anymore but I I used to be the red wine guy I don't know if you remember Resveratrol was uh when I published that paper in 2006 the sales of red wine went up and stayed up by 40% again another industry that should really uh thank thank my lab uh but yeah the it's what you eat and um you can use food as medicine so that's one uh get enough sleep

or at least get very deep sleep if you can uh the Circadian rhythm and the NAD chemical that we've talked about goes up and down during the day and if you disrupt that that cycle Al also affects these seruan genes that we work on the control longevity do you know that if you disrupt the sleep every night for two weeks of a rat it develops type two diabetes in just two weeks that's how important sleep is and I will tell you that for Serena and I we are we're guilty of a lot of travel and

not enough sleep but one of the antidotes has been to get deep sleep instead and instead of sleeping for8 hours with 20 minutes deep sleep we sleep for 4 hours and get an hour or even in seren's case a few hours of Deep Sleep which is the way to go so how do you get deep sleep I don't know if we have time but basically it's um there are some supplements uh Serena talks about that online so you could look up her um she I I take I don't want to promote her supplement but she

has one if your father asked you what he should be taking oh my father let's go back to him because he's the Beacon of Hope when I call him up in Australia which is pretty much every day uh I ask him how he's doing um not not not because I care but because it would look really bad if he got sick I'm joking I'm joking I really do care um but I am happy every every time he says uh the worst thing that that I've got is uh a cold um so anyway so my father

in addition to doing all of that he does get a good lot of good sleep he doesn't stress about anything um and then he also takes a at least a couple of main supplements three actually um we talked about metformin so metformin he's been taking uh two grams of uh cuz his blood sugar was going up like most people's uh and he's now no longer has type two diabetes he's cured that um he takes nmn at 1 gram a day uh the supplement and so that's just swallowed and then he also takes this red wine

molecule not through red wine but purified form please don't try to get it through red wine you'd need to drink 200 glasses a day gallons which I don't recommend I you don't even recommend one anymore a day but yeah he takes her veritol and and you might say well what are these molecules doing well there are enzymes called cin that control the epigenome right coming back to the information Theory of Aging cerin are the sir in the name stands for silent information regulator and these were discovered close to 35 years ago and no one paid

much attention to the word information but it was right there in the name and these cin they defend the body they stop the corruption of the software and they also tell the body how to repair itself by talking to a lot of other different proteins chemically so Ned is their fuel NAD makes cin work it's how they function and as we get older we make less and less by the time you're 50 you you have half the levels you did when you were 20 so nmn is the molecule that my dad takes we know from

clinical trials that taking a gram of nmn raises NAD back up to levels when he was 20 or more so anyway so that's one thing um and the other is the r veritol r ver also acts on the cin um particularly cer1 which is the main one that works on the epome and Resveratrol and we fought with our colleagues about this including fiser who said we were wrong um but we we have shown that the molecule Resveratrol physically attaches to the enzyme and makes it more active like an accelerator pedal so think of nmn or

NAD as the gas for the car and res trol is the accelerator and together they have the best effect we think and so what is your what what's the most exciting thing you see happening in the next five years aging research yeah um well I like to talk about reversing aging though I get a lot of push back from Mostly from my colleagues who say that's an exaggeration but in my lab where you know we're often years ahead of what we talk about we reverse aging every day it's not a question of if it's just

that it's that we do it now the question is is it is it safe I don't know that for sure but we've blasted mice with age reversal technology for the whole life and the only thing that happens is that they live longer uh and they have better eyesight and run faster we don't see any cancer uh we haven't tested running but we'd like to uh so I I think to get to your really to the point of the question uh I think that there'll be in the next 5 years fingers crossed uh one or more

of the clinical trials on age reversal epigenetic reprogramming as we call it technically will be shown to work and hopefully get on the market so that doctors can use it for a variety of conditions from rare diseases through to the general population at their discretion I don't think it'll be on the bottle it won't say anti-aging but it could say treatment for type two diabetes or Alzheimer's that's the exciting part for me David is that it directly into a lot of the other things we're spending a lot of time treating uniquely it's really part of

a system well that's exactly the point I think if there's one thing to take home today and perhaps discuss with your physician it's we we've spent the last 200 years with modern medicine addressing individual diseases thinking that we need a different medicine for each one because they look so different Alzheimer's doesn't look like heart disease well a little bit but not much diabetes wound healing loss of hair gray hair but what I'm saying is according to the theory is that all these diseases have the same underlying cause the majority of these diseases is caused by

information loss of the epigenome and that we can reverse those and that the same treatment that will cure hopefully Alzheimer's will also cure any other ailment that you have from old age that's the big deal and that's the prospect that we're working towards uh I think from here we'd like to move to questions I think we just I I can't imagine a better way to provoke the conversation uh what do we we have Runners why don't we start with down here and then we'll move over there my question is what wait just wait one second

if we wait oh thank you I appreciate it um what do you think of the work of wter Longo at USC and some of the things that he's suggested relative to Li liting calories Etc yeah um so Volta Longo is a good colleague um who started working on yeast when I did so we've been friends for a long time he showed many years ago that restricting the calories of yeast cells makes them live longer and now um professors and talks about uh fasting diets and in fact he invented the term fasting mimicking diet and he

has he has started a not for-profit organization that sells a product that that mimics fasting um I can I can't talk about his product but I can say that some of the data that he has that he's published looks really interesting for cancer for example but also it brings up a bigger question which is um should you fast um and I'm a proponent of fasting I try not to eat three meals a day I think that's too much for most people in there uh over the age of 40 um it's different if you're you know

an athlete but for most of us who live a normal lifespan lifestyle um three meals is too much um I'd prefer if I could eat one meal a day um I think that is very healthy and I'll just give you one study that made me believe this it is in mice but there are some very good uh studies in humans now um my good friend Rafa Tabo at the NH he took thousands of mice and he gave them different diets he was looking at whether reducing fat reducing sugar or reducing carbohydrate would make mice live

longer and then he could say ah here's the optimal diet for a mammal but he also did something very clever he divided those groups also in two and gave half the mice food all the time whenever they wanted it and the other group he gave it to them for 1 hour a day so you can probably guess the result it didn't matter what the mice ate the ones that lived longer by a lot by 30% were the ones that only ate 1 hour a day even though they ate almost the same amount of food food

so I think it's not just what you eat it's also helpful when you eat and I think having a restricted time window will be beneficial and you know we've looked at look at the history of humans those that have a practice of fasting sometime during the year uh seem to be the healthiest maybe back there mean you can reach them yeah thank you thank you uh on behalf of everybody for relentlessly pursuing your passion and purpose for 20 years but also making it available to folks who can participate in the research and take things like

B foreman and do that now instead of waiting sorry if you couldn't hear me um thank you we can hear you like our friends in the frontier of AI they've received some criticism about what the world is going to look like when AI hits how should we think about what's going to change and what's not going to change if lifespan doubles in our society everyone wants their their parents and loved ones to live but on a macro level yeah boy that's a great question um and and I I have a lot to say about it

I'll try to be brief I just want to get back to the fasting for a second because I wanted to mention mention the reason fasting works we we now believe is it turns on uh the ceran activity so you'll will raise your NAD levels naturally by fasting um and turn on these longevity defenses so we call it hormesis what doesn't kill you makes you fitter and stronger and probably longer lived so what what does the world look like if we doubled the human lifespan well the first thing I want to say is um I don't

think we're going to double the human lifespan anytime soon it'll be gradual um we might get there one day but you know adding another 5 years is it would be great news uh but what does the world look like first of all there's the social aspect I think that every human life is valuable um it's not about keeping people alive for longer it's about keeping them disease free for longer so we we all know people who have spent the last five or even 10 years of their life in a state that you wouldn't wish on

your enemies that I want to get rid of I want people to live till the last day as productive and happy and healthy and less of a burden on their families as possible and it's true the longer you live the less burden you are on on family and the and the country you die quicker um sometimes just overnight for no apparent reason so that's the goal um because I don't want you or or anybody you tell this to to get the idea that we're going to be a nation full of people with Alzheimer's that's the

opposite of what we're trying to do here in fact in my lab if we can't preserve the age of the brain or the health of the brain then uh then we don't work on it um what does a world look like where everybody lives twice as long well it's hard to imagine really uh we have done studies of what it would look like at least in the us if we extended lifespan healthy lifespan by one year or by 10 years economically it would add $86 trillion to the economy um for one year and 365 trillion

for 10 years that's in the long run that would be as big a saving as if we uh we no longer spent money on the military that's a big deal um but this would free up money to tackle climate change and other things we need to do it's not uh it's not small numbers um in a world where we live twice as long I think you you'd want to choose your partner as well um you'd you'd be able to one of the things that I really like about the idea of of people living longer is

there's so much wisdom that's accumulated both in in history of memory and and experience and I know this as I get older decisions that I can make in like that I it would take me months to figure out when I was younger and that's that's a great loss everybody is uh is a great loss that dies but keeping people healthier they can take care of the great grandkids they can be productive they can be wise and imagine we could have a congress full of people who but maybe maybe just to add to that David you

could talk a little bit about there is a two class problem right now in terms of increasing lifespan and we're I think it's the rich people have added about six years of life and poor people a lot slower and it's it it got bad during Co and it's but it's pretty consistently a two class problem and I think as you think about lifespan and extending how do you how do you think how do we address that particularly in the US where it just feels like it's more that that problem is more extreme right and it's

becoming even more extreme um there's there's a world in which people can afford to have the best medical care and can see longevity doctors and get the right drugs and they get full body scans and DNA tests that'll essentially prevent cancer in fact I I believe with the right resources we have enough technology that you don't have to get cancer or heart disease um because you can monitor it very very carefully or if you do get them it will be unlucky that's a world that I see a lot Serena and I you know we see

we see fir out of that but that's that's a small percentage of the world I think most of us here are privileged to be in that world if we choose to but then there's the rest of the world that really has no idea they they don't even know how to eat good food let alone afford it so that's a real challenge it's going to take you know not just good science but a lot of good education some new laws I think to to restrict or make more expensive really toxic ultr processed food I'd be in

favor of that as well that is easy uh at least theoretically easy um but yeah it's a problem and one of the things that I try to do with Serena and Serena was on the road with me almost 300 days last year educating the world as best we can about what can you do just the small things that can make a big difference in health even if you don't have access to MRIs and this kind of stuff um but yeah it's it's not a problem that I think will be solved overnight clearly um just one

final thought on this um all new technologies are for the wealth right the R Brothers didn't make plans and everybody not everybody but most people didn't have access until you know the 1960s and 70s and even now uh it's still fairly expensive for most average people digital you know flat screen TVs these are technologies that start off you know I remember going to my uncle's house and seeing a flat screen TV and it was $25,000 and it was it was magical now you can get them to $250 I think that's what's going to happen here

the technology that we are inventing now even though the early products could potentially be a million dollars to cure blindness hopefully not but let's say that they're going to be certainly hundreds of thousands of dollars that's because the ear for the early adopters well worth it if you're blind right but the work that we've been doing in my lab is to bring that down from a million dollars to $100 and we think that's also achievable it's amazing maybe uh bring thank you I hate to take I we just hope we just sure so we get

get get the question for everyone try be quick so no that's okay I just want to again thank you this is so interesting and so important and we've learned so much and uh the question I have is maybe I could just look it up but I want to ask you what are the how many milligrams of met foran reest as veol and uh what was the Emin and M how would we know how much to take if I I'll be brief and I get asked that every time I'm on stage the and it's okay I

do take some Flack for for doing this by the way so it's not it's not criticism free but I do feel like I have a public service at least to talk about what I what I do and my father does um if you have my book or listen to the listen to the book on audio and you know it's it's 12 hours of my voice unfortunately um on the in the book version it's page 304 I list it all out uh but you what what seren and I do we we we uh and this is

not for everybody remember everybody's different so it's not a prescription consult your local physician also not a doctor do this under supervision make sure you get blood tests because you need to know if it's affecting you positively or negatively um um what I was taking when I wrote the book um and I've been trying out various things but when I took the book wrote the book which I still think is valid uh a gram of NN a gram of metformin and roughly a gram teaspoon of resveratrols pretty easy cocktail um yeah beware forman's a drug

R veratrol and enen have not been proven safe in a large number of people we just have to be very careful when I talk about that um but yeah please do your research there's lots of good information out there about these molecules I would go to pubmed.gov that I do talk about these topics in more detail is it shorter than the 12 hours of listening to you you can choose either I would say read the book because it gives you a foundation of knowledge that you probably can't get a it really does the book is

called lifespan maybe one more a few more questions and then we'll go back yeah hi I'm curious I full disclosure was formerly with spark Therapeutics and one of the things the research was great lot of it was going on how are you now thinking about partnering with the big pharmas where you are going to change and it's a huge paradigm shift in how drugs are marketed how they're priced and it's a threat in Curative when you're bringing something Curative that before was a lifetime of ongoing payments from the patients and just just to so I

understand you're a threat to whom big Pharma and just sick care insurance access to the treatments how you manufacture the treatments oh yeah all of it but we were acquired by the biggest biotech in the you were yeah in the world spark is Big some of it to successful and we were two other companies were looking at it they would have shut us down Ro is funding but I'm just curious yeah with that mindset when you are a threat to their bottom line for sure and you're saying the question of when look out in the

next 5 years how are you thinking about the shift that has to occur within big Pharma yeah wow that's that's a hot button topic um but I'm happy to address it first of all thank you for for doing what you do did uh at spark they developed the first gene therapy for curing blindness and I'm following in your footsteps you I couldn't do what I do without you they uh um and actually Gan is an adviser to us so um the question really is about is is this a threat and the answer is yeah absolutely

it's a threat to a lot of a lot of con uh contingencies um constitutions that the farmer industry is just one and if you look at my career um I've upset a lot of people and a lot of companies and they've come off some of them come after me um and I did have a company that was bought by a large farmer that was shut down and I I have some regrets there um I don't have any evidence that they intentionally shut it down but I think if it was still under my care and passion

it would it would have had a champion but it lost its champion in the big company which often happens right you get new leadership and people move on and then nobody's cares about what what your project is and that happens a lot um yeah so that there has been a threat I I got stuck in the middle of a patent dispute between the two largest farmer companies at the time and uh you know a little old me and my it was brutal because I said company X is wrong and oh boy the internet lit up

with who do Sinclair think he is telling company X that they're wrong uh and you know it took a few years to to prove that what we were right but it was brutal I I had folks from Harvard University come to my office and investigate say what's going on I was worried I was going to get kicked out of the university for what happened it was really tough I couldn't get out of bed for for a week I we felt really quite depressed about it CU as you know I I believe in we should all

work together and we can fight for a better future and when that kind of stuff happens really is is at least for a week it was depressing and then I got out of bed and went back to the lab and the lab is the best place I get rejuvenated by by the kids and their enthusiasm but it is a good point that this is threatening to a lot of people um they imagine the worst they imagine disruption of the industries um and it will happen and the good news is that most large Farmers have their

own longevity projects now and are partnering with people like me and uh they're getting on board which is great I think we have one final question here yeah yes study of the can you hold hold the how far are you on oh how far are you under the cloma because I do have it already how far is to study yeah and what can I do in the meantime well if yeah sure the question the question go ahead joh uh how far are we on the glycom studies um and I think everyone knows glaucoma those of

you who don't um pressure in the eye leads to slow loss of blindness there's very little you can do except reduce the pressure but not all glaucoma responds and not all glaucoma is caused by pressure and right now there's nothing I know that reverses the disease only slows it down but we're talking about potentially a cure uh and so where are we at well in we showed that we could cure glaucoma within 6 weeks in mice back in 20120 uh we showed it with Bruce Cassandra's collaboration um and reported it last year that we could

do it in monkeys which is amazing I'm happy about that result uh and where we're at now is the company that is running this life biosciences which came out of my lab um I'll just remember what I can say and what is confidential I can tell you that the drug substance is now manufactured it's ready to be put into humans we've had discussions with the FDA about whether they like our approach um I was very happy that they were very positive about our approach and they even gave really great suggestions I could you not they

actually have saved us a lot of time and money by insights into how to conduct the trial cleverly and so really what you're asking is when will this be ready the first human if all goes well will be dosed um sometime next year and we'll know pretty soon if it works right we'll just wait six weeks and do an eye test I think we'll know and uh so by the end of next year I will very likely be able to tell you if it works now there's a a second phase of all drugs where you

go through a much larger group will probably go from uh what's called from a phase early Phase 2 to a phase three before it gets on the market um and so that's still a couple of years so you know within four to five years I wish it was faster but that's really the realistic time frame given the constraints we have in this country about drug development I'm hoping though that the the other work that we're doing will go even faster um the we these molecules that we've discovered that reverse aging they might um be able

to go even quicker because some of them are are readily available and we'll see maybe we can have an off-the-shelf Glaucoma treatment too so with that I think we have to wrap it but David thank you so much thank you so much thank you John