David Sinclair: Can Aging Be Reversed?

hi everyone thanks for coming I hope you're doing well and feeling fine I've made it my mission to keep you that way and let me tell you how I'm doing so I'm here to talk about a big idea and let me start by showing you the average person not that people from Chicago are average by any means but most people will only live thirty thousand days so my big idea is that it doesn't have to be this way that we can not only live longer than thirty thousand days or we can live healthier much more productive lives and compress that last period of our lives the morbid state into maybe a few weeks sounds crazy right but scientists like myself around the world are doing this all the time in their labs in model organisms like mice and rats and even monkeys so it's not crazy it's just a matter of how soon will this actually happen and we're very very close let me tell you how close we are so I come from Harvard Medical School I have a team at Harvard and also in Sydney Australia of about 30 young scientists are working very hard to make this a reality and if you haven't been convinced by other speakers today maybe I can convince you that we should really look at aging as though it were a disease a treatable disease and that one day people will take a pill that will be able to lengthen the productive and healthy period of their lives you might say well why take this approach why don't we just do medicine and medical research the way we've always done it haven't we been great at that so far well the problem with current medical research is that we've been very good at protecting some parts of the body such as the cardiovascular system but very poor at protecting other parts of the body like the brain and so even though we're living longer and longer we're spending more and more of percentage of our lives in an unhealthy state and this is just not the way to go about improving the world the way I see it is that we have to keep all parts of the body healthy for longer and only then can we look forward to playing tennis with our great-grandchildren and seeing them graduate from college so this is my mother I'm sure all of you have people that are very close and dear to you he would like to see around for longer and certainly not in an unhealthy pain full state or having lost their memory as typically will happen as we get older so my mother is a typical human being she grew up in Sydney Australia and a little suburb called Strathfield she went through the 60s like some of us she was very fortunate to find a husband who stick has stuck with her for 49 years and she had two boys myself included so there's my mum hiding in the back but even though you wouldn't know it my mother was the matriarch she's always been the leader we turned to her for her opinion and she's led us for the last decades so in 1994 everything changed she developed cancer lung cancer as you can tell from this x-ray image with the tumor at the size of a grapefruit in one lung the surgeons the doctors said it's non-responsive to chemotherapy we're gonna cut it out we've you better get your things in order you've got less than a year to live so my mother underwent what's called a pneumonectomy and tried to get by on one lung so at that point I was studying little yeast cells getting my PhD in Sydney Australia so here's a picture of a yeast cell and what I was noticing was that some of these yeast cells were getting old and this is an example of an old yeast cell he's getting larger she'll slow down she'll become sterile pretty similar to to many of our lives and the idea was back in the early 90s was that maybe we could understand aspects of Aging in our own bodies by studying these little yeast cells these are exactly the same cells that you use to make bread and beer and I learned about a professor who had just started up a project at MIT and I asked him could I please come study with you and I was the first a postdoctoral researcher to join the lab of Lenny garantie at MIT to try and figure out why do ye cells get old and how can we slow it down and I've been working on this ever since clearly some of us have have aged since then so what did we discover well there's been a remarkable advance in our understanding of what causes aging and how we can regulate it and what we learned from those yeast cells that also appears to be true for ourselves in our bodies is that is it isn't old genetic it's not just about how many mistakes are in your DNA or even what genes you have there's a new phenomenon known as epigenetics and that's basically a term that describes things that happen above the genetic landscape how the genes are actually switched on and off and what we found with the yeast cells is that when they're young they have a certain program of which genes are on and off and that keeps them youthful but as they get older the genes that are supposed to be on some of them get switched off and vice versa and that was what was causing Aging in these yeast cells and we could very rapidly now that we understood what was going on we could counteract that and slow down aging in these yeast cells so now fast-forward what is it now 20 years we now have a much better idea of how this all works not only in those yeast cells but in our own cells as well we think that something very similar is occurring so have a short video to show you of what's going on inside we think inside our own cells so inside each of our cells we have a nucleus and now these chromosomes and if you unravel a chromosome what you actually get isn't just a string but actually beads on a string so our DNA is wrapped up in these proteins called histones as you can see here they're shown in pink what's interesting about that is that these histone proteins control which genes are switched on and off okay and when we're young as I mentioned important genes get switched off and certain genes get switched on so if you're a gene that should be on in the liver you want it on the liver you don't want to run in the brain what happens over time we found is that as you can see in in the diagram here that these proteins that hold the DNA together become chemically modified and now a gene that should be off become switched on and the opposite as well can happen so what's important about this well the major implication is that aging should be reversible if we can bring that DNA back into a closed conformation we can reverse this process we should be able to make an old cell young again and that's what we've been working on about the last 10 years in mice and human soul so one of the molecules that we found about 10 years ago now is or was called resveratrol I'm sure many of you have heard of resveratrol it's this molecule in red wine and we found that resveratrol turned on the pathways that controlled these histone proteins and packaging of the DNA and we fed resveratrol to the yeast cells and they lived longer about 30% longer we fed resveratrol to worms and flies we fed it to mice and the mice were healthier they were impacted seemingly immune to the effects of obesity and later molecules that were even more potent powerful than resveratrol more drug like molecules were able to extend the lifespan of those mice and keep them healthier and younger for longer it was a really exciting time you can see that even Fortune magazine put up put the story on the cover yeah I was feeling pretty good myself this is now 2006 I started a company that was working on this these drugs were being developed they were entering human trials so here's the molecule this is the resveratrol molecule from red wine as soon as we made this discovery I started taking this molecule I figured what have I got to lose I know what's gonna happen if I don't take it and that's not pretty surprisingly my wife insisted demanded that she have access to this molecule my mother my father they all insisted in fact my brother was quite upset with me recently he said what am i the negative control in your experiment so he's on it now too so we have no negative control anymore but my whole family has been on this molecule for in the case of my parents and wife over 10 years now we don't know if it's working it's a small sample of course but we do know that it helps animals and even monkeys so we're optimistic that it's going to help and remember my mother had lung cancer in 1994 and I actually came to the United States thinking that I would never see my mother again unfortunately she did pretty well you can see here this is just a from a few years ago she was able to see three grandkids we've got here Madeline my oldest child Natalie and Benjamin who's actually just backstage here today a budding scientist himself so this is wonderful here we have a cancer survivor that has beaten all the odds in fact the doctors have been puzzled how do you treat somebody who's only had one lung for 20 years they even put her on viagra which I was trying to get some from my mom on the internet and I kept getting these pop-up ads for Viagra and I was thinking no it's not for me and I imagine nobody would have believed me it was for my mother um so maybe it was virtual help maybe it didn't but she's done she did did well and there's a new study that we just put out just at the end of last year and we think we've found an even better way to activate these anti-aging pathways to put the genes back in their youthful configuration and this is a molecule called nmn it's full name is nicotinamide mononucleotide but you don't need to remember that but what's important to know is that annamund busts a molecule in our bodies called nad and NADH is needed for every reaction every important reaction in the cell but it's levels decline as we age to about 50% when you're elderly and this is a really bad thing we think and so what we did was an experiment where we took old mice that were 2 years old the equivalent of about a 65 year old human and injected it for a week with this nmn molecule and raised the nad levels up lo and behold those male mice became more youthful in fact when we looked at the muscle of those mice we could not tell the difference between the two-year-old muscle and a 6 month old and we were able to report in the journal Cell which is a decent journal that we were able to for the first time reverse aging in a tissue and we think this is just the beginning so nmn is very exciting and I was trying to make a lot of it so that my mother could be helped by it I thought that raising the energy in her cells would be wonderful she was running out of lung capacity in recent years the other thing that's amazing about Anna man is that it doesn't just work seemingly against reversing aging or to reverse aging but we also have tried it and this is from the lab in Australia where we fed mice that have induced cancer in the liver these are livers and we find that Anna man just in the drinking water of mice is extremely protective against this very aggressive cancer in the liver so we're excited about the possibility of this new molecule and molecules like it to treat diseases of Aging but also to lengthen healthy lifespan and these molecules are entering clinical trials next year so this led to some headlines there was headlines about reversing aging it's a certainly interesting if it's possible to reverse aspects of aging it was a great time I again it was very fortunate to have have lived through this and seen my my science I reached the cover even of Time magazine and it was at this point this is not me by the way if you're wondering but yeah you know this happened this year actually and it was a it was it's been one of those years where I'm extremely grateful certainly being one of the highlights of my my life so far it's also been one of the lowest just exactly four weeks ago I got this email from My Father I'll just read it briefly to you David I don't want to scare you but mom had a cardiac arrest I'm in the hospital actually she stopped breathing and that led to her cardiac arrest he ends by saying I'll let my brother Nick sleep I'll need him tomorrow I'll keep in touch so what did I do I immediately collected all the enema and molecule that I could gather from the lab and I put it in a FedEx envelope and I shipped it to Australia in the hopes that it could be given to my mother to try and rescue her I also bought a plane ticket most expensive plane ticket I ever bought not that it matters but $30,000 for a plane tickets quite a lot I jumped on a plane I got down to Australia as fast as I could and my mother woke up and I took this photo of my mom she was doing she's doing great there's my father there we're all extremely happy to see her happy and awake and in fact I accidentally touched the video button as you tend to do on your phones and and captured us all laughing and being really happy we thought that my mum was gonna be fine you can tell that she doesn't seem that old she's barely got a grey hair at her age of 72 unfortunately that was the last video that was taken of my mum and it's about 10 minutes later she had a flame caught in her throat and right in front of us was unable to breathe and I was unable to help her and I felt extremely helpless and all I could think was I should have worked harder but what it's done for me is it's led to greater resolve I now get up in the morning and I'm reminded that people only get 30,000 days to live and many of those days are not in perfect health by any means and I believe that it doesn't have to be this way it doesn't have to be like that for any of us in this room and I'm hoping that our generations will be the first to reap the benefits of these this new technology so what is this new technology I've told you a couple of compounds that I'm working on but there's now a worldwide effort of scientists to try to slow down aging and improve health we have Google investing in this we have GlaxoSmithKline who we've invested they've invested close to a billion dollars in my research and these molecules that I'm showing you here are currently in human clinical trials these are some of the first ones that were based on the resveratrol molecules from red wine but we can do better it's a race against time for all of us and we may be too late for it to help ourselves in fact less than half a percent of the research budget that the National Institutes of Health goes towards understanding aging at a fundamental level which i think is crazy given that is it is one of the biggest problems that faces all of us in this room and certainly the planet both in economic terms and in socio and social terms so I'm very optimistic though the technology that's coming down the line just makes my head spin the ability to genotype yourself to predict your health to be able to now manipulate certain genes in your body just a year ago there's been a big breakthrough you may not have heard about it it's called CRISPR technology it's going to you know I will bet lots of money that this will lead to a Nobel Prize we now have the ability to go into cells and just turn specific genes on or off at will we couldn't do that a year ago and now we can go in and we can reprogram cells so that they're younger again and we're working on that as well in my labs I'm also optimistic because we have young people who are dedicated to this cause this is my son Benjamin who did a 23andme test is a genetic test and we were able to look at what genes were passed from his grandmother my mother through to him and actually we found a mutation in my mother's genome that predisposes her to lung cancer which I also carry so I think the future is bright it's just I can't believe that we're not all standing up screaming for more research in this area because time is really running out but I wanted to say thanks very much and I can't really say can't think of anything more important than looking forward to a future where families get to see five or six generations stick around and be healthy and happier at the same time thanks a lot

Channel: Chicago Ideas

Views: 142,334

Keywords: David Sinclair (Organization Leader), Harvard University (College/University), Genetics (Field Of Study), College (TV Genre), University (Building Function), Health (Industry)

Id: AiCvqnUIe04

Length: 18min 36sec (1116 seconds)

Published: Wed Feb 04 2015