[Music] welcome everybody so I’m looking around it I see not that many very young people so this talk should actually be of great interest to us so I want to see a show of hands how many of you would like to reach 120 honestly how many of you it’s about a third maybe if that a quarter okay so let me change the question how many of you would like to read 220 if you could still feel the way you do today exactly alright so today I’m wondering what I’m going to tell you about is technology partly from my lab but partly from labs around the world that have really made a breakthrough in understanding why we age and how to control this process and it’s just reached the point now where it’s commercializable which means more importantly that there should be medicines coming online and there it may even be method medicines already prescribed herbal to people today that can slow down aging the important point here is that I’m not telling you that we’re all going to live forever but I what I can tell you today is that we have the know-how now to make people live longer and importantly healthier lives okay that’s really important because there’s no point extending lifespan if we’re not going to be healthier because over the twentieth century mostly what we did was knock one disease on the head at a time we call this whack-a-mole medicine and what that’s done is it’s made us live longer but not better and what we’ve got is a great burden of healthcare across the planet not just in what we call the developed world but the developing world most of the world is is aging rapidly and this is actually one of the biggest challenges on the planet it’s as big a problem for the economy world economy as global warming and what I hope to make the case today is that not only will this help individuals and the economy but this is also going to help the planet because saving trillions eventually tens of trillions of dollars in healthcare costs at the end of life by compressing it down into a very short period let’s say a month of illness we’ll free up money across the planet that can be used to save species and protect the planet the way I think we would all agree is important so we all have family members we love these are some family members that I’m very close to I’m genetic related genetically related to this line of people on the left is my grandmother Vera who insisted I call her Vera she stayed very young at heart up until the very end she escaped Hungary in 1956 and lived a standard twentieth-century life into her 60s and 70s she was vivacious she was kicked off Bondi Beach for a bikini in the 50s but towards the end of her life at the last 10 years were really hard to watch as a young boy and this is not something you would wish on anybody not even your enemies and really towards the end she’d given up she said this is just the way life goes but I refuse to accept that aging is just something we have to live with because 100 years ago we used to say the same thing about cancer and heart disease and Alzheimer’s and if you’re wondering why don’t we just focus on cancer heart disease and Alzheimer’s that’s great my mother died of lung cancer I’m the first person to say cancer is a worthwhile cause but if we stopped cancer today the average life span on the planet would increase no more than two and a bit years because all causes because aging is going up all the time and all diseases are increasing exponentially so even if you stop one you’ll die shortly after from something else so we need to address diseases at their core in fact my mother died from lung cancer ostensibly because she was a smoker and her risk went up with smoking fivefold that’s terrible fivefold of course that’s going to potentially lead to death but from age 20 to 70 your chance of getting cancer goes up a thousandfold but we don’t address aging in fact most people don’t even realize it’s something worthwhile doing so I hope today I can change that so my father is my grandmother as you can see died in 2015 and I was a fairly typical and long lasting painful drawn-out process my father is still alive he was born as you can see in 1939 and he’s just turning 80 and as you’ll see he’s leading a very different life as different as I think the future generations will lead going forward so the question is why do we age and I think a lot of people don’t even ask that question it’s just something we live with we see it every day everything dies why do we need to understand aging well we can’t address aging we can’t slow it down we can’t prevent diseases until we truly understand what’s going on so one of the breakthroughs that’s come through in the last 20 years in aging research is to understand that the body has inbuilt defenses pathways that you can activate by being a little bit hungry I skip a meal whenever I can it’s hard but I try you can exercise they turn on these anti-aging pathways and eventually we’ll have medicines that can do the same but we need to understand at a fundamental level why do we age just as much as the the Wright brothers need to understand aerodynamics and why it is that birds can stay in the air and I think that we’ve had a breakthrough in the field and understanding at the fundamental level why we age now if you go to the literature right now you’ll see that we people who study aging generally agree that there are about eight or nine causes of aging mitochondrial dysfunction telomere loss epigenetic changes but we’re still trying to address each cause separately like building nine dams on nine tributaries but is there a unifying cause of Aging I think there might be and let me tell you about that at the root cause of Aging I think lies a loss of information in the body we live in the information age and it’s right in front of us so a little bit about information before I get into biology so I’m inspired by this guy here this is Claude Shannon in the 1940s he was publishing on how to communicate information across long distances and in space in time as well without losing that information and he knew this to be very important because he had seen in World War two what happens if signals don’t make and so he developed a mathematical theory of communication and it really transformed the world in this diagram what you can see is that there is a transmitter of information and a receiver and in between those two points is noise now there are two types of information there’s analog and digital we’ve transformed our world recently by going to digital which is very a very accurate way and a relatively lossless way of transmitting information the other thing that was a breakthrough in this paper was he said well if the if the information doesn’t make it to the end intact maybe what we should do is have an observer that holds the original information just in case we lose it along the way and then we go back and retrieve it and that was a key breakthrough that led in fact to today’s internet we have the tcp/ip protocol that allows us if our email doesn’t make it or a photo doesn’t make it we go back and get the rest of those bits and bytes so that’s transformed our world electronically but I think also if we apply this theory to biology we have a chance of not just slowing aging but actually reversing it because I think that our bodies may actually have an observer that holds the information to be young again so how is information stored in our bodies well actually there are two types of information there’s the genetic information of course in DNA there are four bases of DNA so it’s a base for digital format and as I mentioned digital format is very good for copying it’s long lasting you can even get DNA out of mummies and read it and we don’t think anymore that the loss of the DNA code is necessarily the key driver of Aging it plays some part but what I would like to argue today and give you some evidence that it’s true is that it’s the other form of information in the body that we lose over time that’s even more important for driving aging and that’s the epigenetic information the cell that’s laid down beautifully during embryogenesis and development but aging starts in the womb in fact and we can now measure the clock of aging in part by measuring the methylation chemical additions to the DNA accumulate over time and you probably know what I what’s on this screen the blue is the DNA and those green are representative of histone proteins that package the DNA and tell the cell how to read the right gene at the right time and that a nerve cell will stay a nerve cell for your life and a liver cell will stay a liver cell hopefully for most of your life the other thing that that I want to mention here is we work on proteins in my lab that control which genes are on and off epigenetic factors we call these genes the sirtuins and they make enzymes they’re very important and they require a molecule called nad and anybody who remembers their high school biology will remember that nad is a molecule is required for life and without it we’re dead in 30 seconds problem is as we get older we think that we have less and less nad so the time you’re my age which is 50 you have potentially even half of what we had I had when I was 20 so sirtuins seem to control the epigenetic information now it’s important to know that epigenetic information is not digital it cannot be it has to respond quickly to the environment what we eat how we’re if we’re running if we’re breathing enough that means it needs to be an analog format and anyone who’s had a cassette tape or even a record knows that analog information can be lost over time it’s very hard to copy it’s very hard to shield from cosmic rays eventually it’s lost I think that’s what’s going on with aging as well so if we translate that to biology what it means is that the cell this is an example on the screen of a nucleus and those lines of the DNA and those blobs are these chromatin factors such as the sirtuins that control which genes are on and which ones are off and those patterns determine sale or identity what we think is happening is there’s there’s noise going on all the time so that cells eventually turn the wrong genes on so that your nerve cells start to feel like they’re more like skin cells and we found that kidney cells start to resemble more like more like act more like muscle cells in the old mouse that we studied one of the things we’ve figured out is what actually can drive that process what is the noise in the cell so by analogy I often describe this as a compact disc system and so for the really young people in the audience a compact disc is something we used to put information on we used to store songs on it it was really crazy we could we can we could fit an entire movie on there it was awesome anyway so what’s important about this analogy is that the information on a scratch compact disc is retrievable in the same way I think that an old cells information is still retrievable it’s just that in an old cell or in a scratch compact disk it’s it’s hard to read the right songs at the right time but imagine if you could polish this CD and get the information back so we’ve been testing this there are two predictions of this hypothesis one is if you scratch the CD or introduce epigenetic noise cause cells to lose their identity will you get aging and then the second prediction is if I can cause aging can I take it away so I’ll tell you some results that we’ve had in the lab that were just writing up for publication now here’s what happens if you scratch that DV butt DVD or the CD you can see that these mice in my lab look very different and you I’m up you may want to ask yourself which Mouse is older it turns out they’re genetically identical and were born the same day but the one on the right has had its epigenome tweaked in a way that accelerates what we think is the aging process now you might be wondering how does this happen well we’ve actually shown that cutting the DNA leads to and the disruption of the epigenome and as I mentioned if you can cause what looks like aging you can take it away potentially so how do you find the original information to restore Seiler identity and the trick was actually to follow in the footsteps of this man on the right which is he is Shinya Yamanaka who won the Nobel Prize for discovering genes that convert adult cells into stem cells so you can reverse aging in the dish but can you reverse it in an animal and so we tested that in the lab we packaged three of the genes that Yama discovered standing for OS k klf4 and socks to these three genes OS k we packaged into a virus there’s a virus here and we can introduce that into an animal and ask does it protect the organism does it make the organism feel young again and in this experiment I’m going to show you what we’re doing is testing something that normally doesn’t happen in an adult animal but only happens in a very very young animal and that’s the regrowth of optic nerves we all know if we have a spinal injuries as we’ve heard earlier from Greg and in this experiment what we do is we pinch the back of the eye and the optic nerve dies back as you can see in the the figure here that that red area is where the living nerves are heading away from the eye but then all of the nerves have died back towards the brain so you can see this dead area on the left but if we turn on these reprogramming epigenetic factors these Yamanaka factors after the break after the squeezing with tweezers what we get is something that would only normally happen in embryos the regrowth of nerves and these nerves actually if you leave them long enough will grow all the way back to the brain now we can also reprogram old mice we’ve taken one-year-old mice two year old mice introduced the virus into those turned it on and within four weeks those mice can see just as well as when they were young compared to young mice so that’s an interesting thing retina can actually be restored in terms of its function not just slow down aging so finally I just want to show you something else I mentioned nad is important for controlling these genes that regulate the epigenome and one of these I don’t know if you can trigger that movie to play but this is a treadmill experiment looking at mice that have been on an nad booster molecule and nad boosters will stabilize the epigenome and make cells younger and these mice if you could see them running the one on the left has been on this molecule just for four weeks and its muscles are acting as though it’s young and can run actually up to twice as far as the control we published this in a journal just last year so nad boosters mimic exercise as we had expected and there are clinical trials now ongoing with these and more advanced molecules so the future looks really interesting we’re close to having molecules hopefully we’ll we’ll see safety and efficacy in these clinical trials but what does the future look like let me just paint that for you so what if we could truly reprogram reprogram our bodies you could imagine not just Bill Murray but all of us could one day be genetically reprogrammed or at least infected with a virus that could turn on these resetting genes and in mice we know that that restores the epigenetic clock you can take the animals back as seemingly a large percentage of their lifespan so what if in the future if it’s safe we all have this what waiting in our bodies and if we get injured we have a spinal injury we just get diabetes we get dementia we take a course of an antibiotic which we actually have Shoen works to induce these genes in in the animal and perhaps that would lead to rejuvenation and you go back a decade or two and then it you aged for twenty years and then you go back to your doctor and get another course of antibiotics and I don’t know how many times you can repeat that but we’ll see so just to finish I want to give us a glimmer of hope here because we all know what’s coming no one else no one gets out of this life alive unfortunately but my father you remember from the first slide he was born at a time when he’s just on the cusp of potentially being able to benefit from these technologies and he’s been taking a couple of molecules that we’ve been publishing on res virtual and nmn is an ad booster now I don’t know if they’re working he doesn’t know if they’re working but what’s heartwarming if nothing else is that he’s now 80 he started a second career this is just an example of six months of his recent life and he’s just he’s wondering what’s gonna happen now that I don’t seem to be getting old and I’m watching all he’s watching all his friends decline at that age so hopefully he’ll continue on I certainly hope so I hope that he gets to spend time with these great great grandkids and impart the wisdom that the older people just haven’t had a chance to do until until recently and hopefully even more so as these technologies come onboard and so what am i telling you I’m telling you that these there are technologies that are just around the corner that could really change the world not just for for families but for the economy of the world freeing up trillions of dollars that could actually allow us to to make this much world a much better place where we could all thrive be more productive and impart the wisdom that I think is a great loss every time someone passes away anyway thank you for listening I appreciate it [Applause] [Music]
Longevity researcher David Sinclair is best known for his work on understanding why we age and how to slow its effects. He believes aging is not inevitable but a treatable condition. In his talk at Science Unlimited 2019, he explained why we age – and how we can reverse aging to extend human healthspan and lifespan.
David Sinclair is Professor in the Department of Genetics, Blavatnik Institute and co-Director of the Paul F. Glenn Center for the Biological Mechanisms of Aging at Harvard Medical School. Science Unlimited is held in Montreux, Switzerland, as part of the annual Frontiers Forum.
Video courtesy: https://www.frontiersin.org