Getting older without getting old - with Andrew Steele

(electronic music) (audience applauding) - Hello, everybody, good evening, thanks so much for coming along and hello to everyone who's watching online who I gather there's quite a lot of you. I'm Andrew and I want to tell you about what I think is the most exciting and consequential science of our time. You can see that my talk is named after my book. It's "Ageless: The New Science of Getting Older Without Getting Old". And I want to show you some of this new science and show you how I think it literally could make human beings ageless eventually. And I also think we need to answer the question of would we actually want to do that? I want to change the way that you think about aging because I think a lot of us think of aging as sort of a natural part of being alive. As you get older, you notice that your grandparents, then your parents, then your friends and yourself start to age. You get wrinkles, you get gray hair. Obviously, not everything about the aging process is bad. You acquire wisdom and experience during that time as well. But I think that aging is our greatest humanitarian challenge. And that might sound like a slightly weird thing to say so I'm gonna unpack that a bit during the first part of the talk. I think a lot of us also think that aging is inevitable. We see it happen to the people around us, but it also happens to animals. It happens to our pets, our cats, our dogs, our mice, our hamsters. It happens at very different rates in different species, but actually, if you've ever watched a pet get old, they tend to get old in a very similar way to the way that humans do. So is this just some sort of biologically universal sort of process of falling apart that we really can't do much about? Well, actually the answer to that is no, because what this new science shows us is that the aging process is malleable. It's plastic. It's surprisingly controllable in the lab. We've got literally dozens of ways to slow down and even reverse this process. And some of these are making their first baby steps out of the lab into actual human clinical trials. This is a really, really exciting time. And I think that's the sort of the combination that makes this such a fascinating field for me. Cause on the one hand, we've got this world's greatest humanitarian challenge, a genuine, huge problem for us to try and rise to. But then on the other side of the coin, we've got this enormous scientific potential, the ability to rise to that challenge. So I just think this is utterly fascinating and I hope that I'll convince you all of that during the course of the evening, but where I'd like to start is right back at the beginning and actually back at the beginning of my career as a computational biologist. So as you heard, I actually didn't start out as a biologist. I did a degree and even got as far as finishing a PhD in physics before deciding that aging was the single most important problem that we needed to do something about. And actually, maybe this was because of my physics training. I'm very sort of numerical and stats driven more than, some people ask me if I've had some terrible experience with death in my youth or something like that and that's what drew me into it. But actually, I changed career because of a graph. So I'd like to show you that graph and show you that although it's a very simple graph, it's implications are absolutely enormous. So the graph looks something like this. Up here you can see that along the bottom, you've got how old you are in years and up the side, you've got your chance of death in that year. Now I think all of us know that older people are more likely to die, but just how much really shocked me. So the line looks something like this. Let me try and explain that by sort of going through it from left to right. When you're born, that year is actually quite a risky year for people. This is a graph for people who are lucky enough to live in the rich world, but even in a developed country, you've got something like a half a percent chance of not making it to your first birthday. And that's obviously cause you could be born with some kind of congenital problem, a genetic defect, maybe you get cancer or an infection very early in your life. But if you make it to your first birthday, actually things keep on getting better and better for quite a few years until you reach the age of 10 and current 10 year olds have an incredible title. They are the safest humans in the history of our species. So if you've got any 10 year old sons or daughters or cousins, let them know this amazing fact, cause they've got a less than one in 10,000 chance of not making their 11th birthday. Now unfortunately, it's all downhill, or rather on this graph uphill from there. So if you are 18, you've got about a one in 3000 chance of dying that year. I'm 36. That means my odds of dying are about one in a thousand this year. And it's worth just stopping and thinking about that for a moment because I quite like those odds. If that were to continue for the rest of my life, I'd live another thousand years on average. I'd make it into my thousand and thirties. So clearly that isn't what goes on. And actually what happens is that after you reach the sort of age 20 or 25, human's risk of death doubles every eight years. This is something that we call the mortality rate doubling time. The time it takes for your risk of death to multiply by two. And if you start off with something that's quite a small number like one in a thousand, you can double it a fair few times before it starts getting scary. So if your 65, your risk of death is about 1% that year. Still not too bad. If that were to continue, you'd still make it into your hundred and sixties. But unfortunately, 1% is now a big enough number that when you start doubling it, serious things can start to happen. If you're 80, you've got about a one in 20, so a 5% chance of death that year. And if I'm lucky enough to live into my nineties and medical technology doesn't advance at all in the intervening time, I'll be somewhere way off the top of this graph. My odds of death in the early years of my nineties will be about one in six. So it's life and death at the role of a dice. These are odds I really don't particularly want to run. And so you can look at this graph in a couple of different ways. You can look at it as a human and you can think my God, that's terrifying. I've got this enormous wall of exponentially increasing mortality coming at me. Or you can look at it as a physicist and you can say, gosh, this is actually really fascinating. What is it about human biology that means we have this astonishingly synchronized increase in all kinds of things going wrong with our bodies at the same time? And this is a really, really universal phenomenon. If I were to get back to the 1600s or if I were to go exploring in the Amazon rainforest and find some undiscovered tribe, their absolute risk of death might be quite a lot higher so they have a shorter life expectancy, but they would have that same eight year mortality rate doubling time. This seems to be an intrinsic fact about being human. And so you've gotta wonder what is it that's going on in our biology that makes us so much more likely to die as we get older? What is this universal ticking clock in all of us? And most excitingly, could we identify this ticking clock and could we do something about it? So that means in order to answer that question, we're gonna have to ask another question. And that question is what is aging? And there are a few different ideas that I'm gonna come up with on this slide. The first obvious one, I've already mentioned it. I think it's the first thing most people think of when you mention aging to them. It's the cosmetic external stuff: the wrinkles and the gray hair. And while these can be distressing for some people, as a sort of biologist and wannabe be a helper of the world through medicine, these aren't the things that concern me the most. The most concerning things are what are called the age-related diseases. These are diseases like cancer and heart disease, dementia, stroke. Diseases that are substantially more likely as you get older. You can do things that increase your risk of these things. You can smoke and increase your risk of lung cancer, for example, but ultimately, the single biggest risk factor for all of these, that sort of medical jargon, is just how long ago you were born. It's being an older person. Then there's the stuff that sometimes gets you a medical diagnosis, sometimes doesn't, and I've sort of grouped these together into a category. Overall, it's loss, it's loss of your vision, your hearing, your memory, your muscles, all of these different things. And as I say, sometimes this'll be enough for a medical diagnosis, sometimes it won't. It's just a sort of problem that you have to live with. And overall, this category is sort of loss of independence. It means you can't do the stuff you wanna do. You can't play with your grandkids. You can't get up the stairs. You can't get around the house. You can't do your hobbies. You can't eventually do everyday tasks. So that's the thing that I think aging really sucks from all of us ultimately. And finally, we've got the stuff that isn't strictly aging related per se, but is much, much more serious as you get older. So these are things like infections and injuries, things that a younger person would basically just shrug off. Imagine if I broke a bone, I'd probably just end up having a plastic cast on for a few weeks and basically being fine. But if a 70 or 80 year old breaks their bone, they often break their hip, they go into hospital, it's a very serious thing. They can be in a hospital bed for a few weeks and lose a load of muscle mass. They might contract a hospital-acquired infection. And ultimately, something like breaking a hip can begin a spiral that ultimately goes on to end their life. So this is something that's much, much more serious as you get older. And to go back to my favorite graph, I guess, now we understand behind this, you might not be worried about dying itself because maybe there's just, you know where you're going and there's no particular pain on your part. But what this really represents is a huge increase in the risk of all different kinds of suffering. So I'm gonna slightly change the graph. You've still got your aging years along the bottom, but up the side, you've got your chance being diagnosed with a particular illness. And we could look at cancer, heart disease, stroke, dementia, and what you can see is they all follow slightly different patterns, but broadly speaking, it's the same thing. It's this exponential increase with age. Actually dementia is particularly terrifying, almost unheard of before the age of 60, unless you have a genetic predisposition to it. But after the age of 60, the risk of dementia doubles every four and a half years. So dramatically faster than the risk of death itself. And obviously, dementia is a disease that a lot of us are rightly very scared of. So these are the sort of strictly age-related things. To add another one, this disgusting, mucusy green line here represents chest infections. This isn't just a little sort of cough, or a sneeze, or a cold. (audience member coughing) This is a proper thing that gets, right, everyone in the audience now coughing. (audience laughing) Some kind of reflexive reaction. This isn't just a little cough. It's something that gets right down into your chest. Really, really quite unpleasant. What you can see is that even in your sort of young middle age, when your chances are lowest, you've still got a one or 2% chance per year of getting a chest infection. But when you're young or when you're old, what that means is either you've got a naive, underdeveloped immune system or your immune system's starting to weaken because of the aging process. You're much, much more likely to get one of these diseases. And the worst thing is that at the end of life, obviously you're much, much more likely to die from it as well. And there is one disease, of course, one respiratory infection, in fact, that we can't really go without mentioning even though we're all trying to forget about it. This is your chance of death if infected from coronavirus. And it looks something like this. Again, sort of boringly familiar by this point. It's another exponentially increasing graph. Your risk of death from coronavirus doubles about every six and a half years. And that means that if you are 80 and you catch coronavirus, you are literally hundreds of times more likely to die than someone who's 30 and catches that same disease. Now the good news is I hope most people in this room have been vaccinated and that means that curve has shifted quite a long way to the right. It effectively takes 20 or 30 COVID years off your age. And that means you're much, much more likely to survive. Much, much more likely not to end up in hospital as a result of that. But nonetheless, it's still much riskier to be an old person, even if you're triple vaccinated, compared to a younger person who catches COVID. There's still this enormous exponential increase in risk with age. And so what it just makes me think is aging has this enormous potential and sort of to skip ahead a little bit, imagine if we could come up with a treatment that could reduce the age of your immune system by 10 years. And imagine we could give that to everyone in the population. We could have that ready for the next pandemic. That's the ultimate protection against almost any virus that might appear or almost any other kind of pandemic infection, because we'd all just have a much stronger reserve, much stronger defenses to try and fight that virus off. So to return to this, I think what this graph really does is it explodes a myth. And that myth is that death by, you can die of old age. You used to be able to write that on a death certificate, but it's no longer allowed because actually most people die of something quite specific. And most of these diseases, I'm sure all of you have friends or relatives who've had one of these things. They're not necessarily a painless way to go. You don't just fall asleep and not wake up the next morning. Cancer can have years of grueling chemo and radiotherapy. Heart disease slowly robs your ability to get around. It might stop you getting up the stairs. And eventually, you're hardly able to move at all as a result of your weakened heart. So all of these things have huge, huge social and individual and sort of moral consequences. So this is why I think that aging is our greatest humanitarian challenge cause behind those death statistics, even if you are sort of unworried about the death itself, are years, perhaps even decades of suffering that come before that. So you might be thinking, Andrew, maybe this is a problem that we in the rich world are lucky enough to have. This is something that we're sort of perversely lucky in that we live long enough to experience some of these conditions. And what I'm gonna do now is I'm gonna do a quiz. So I'd like everyone who's physically in person to stand up for me. So please get out of your seats. Everyone on the live stream, you're gonna have to just think about this at home. So I want you to imagine, the quiz question is what is global life expectancy? How many years does the average person on planet earth live? So not just in the rich countries, but all around the world. And what I'm gonna do is I'm gonna flash the numbers up on the graph, and this is a free starter. Nobody sit down now because if you thought that global life expectancy was 40 years or below, you would sit down now. Good, no extreme pessimists in the audience. And what I'm gonna do is I'm gonna keep on incrementing that up. When you think I've gone past global life expectancy, please sit down for me. So 50 years, any takers? Remember this is all the countries, not just the lovely, posh ones like the UK. Anyone for 60 years? We've got a few. So I'd say maybe a third of the audiences has sat down now for those watching online. Anyone for 65 years? We've got a few more. This is like a really grim auction, sorry. (audience laughing) Anyone for 70 years? We've got most people sat down now. There's still a few sort of diehard, diehard's probably the wrong word. (audience laughing) We've got some optimists in the audience. Anyone for 75 years? This guy. (audience laughing) 80 years? No, even he's had it now. And just for free. Yeah, 85 years is not the answer. The UK life expectancy, by the way, is about 80. This chap is going for broke. (audience laughing) I'm afraid that's the last one so you're gonna have to sit down, sir. The actual answer, drum roll please. And I'm afraid most of you got it wrong is 72.6 years. - [Audience] Oh. This was back in 2019. Obviously, things have had a bit of a rough couple of years in terms of global life expectancy and the statistics are still coming in. What this means is most of you got it wrong. And actually, you shouldn't feel bad. You shouldn't be too hard on yourselves. If you present this as a multiple choice question, only about 30% of people get it right. And if you present it as a multiple choice question to university students, only about 20% of them get it right. So education clearly leaves something to be desired. I think what that really shows us is that we've all got this picture of a sort of vast developing world where things are much, much poorer. There's much worse sanitation. There's much worse access to food. That kind of stuff. We imagine that these countries have much, much lower life expectancies than ours do, but actually, there's been a huge success story in the last 50 years of countries rapidly, rapidly catching up with the rich world. The world leader is Japan, which is something like 85 years of life expectancy. Here in the UK, it's about 80. A country like India you might think has a very low life expectancy. It's actually 69 years now. So these people in poorer countries really are living an incredibly long time cause we've done very well conquering things like infectious disease in those countries. Now the good news is that means that most people in most countries are living longer, healthier lives than ever before. And I honestly think this is probably the greatest achievement in human history. But the flip side of it is that if we go back to my favorite graph, with apologies, then most people in most countries are living long enough to experience significant effects of aging. They're climbing a fairly long way up that curve. And obviously, this problem is only increasing as the global population ages. So if we try and translate that into what it actually means from a global statistical point of view, every single person on this image is a thousand deaths per day. So 150,000 people die every single day on planet Earth and of those deaths, over 100,000, so more than two thirds, are deaths due to aging and that's because they're deaths from cancer, heart disease, dementia, all of these to diseases that aging causes. They're excess deaths due to something like COVID, which isn't caused by aging per se, but is made worse by it and so on. And that means that aging is by far, even if you get all of the other causes of death, add them together and double it, you still won't get as many people as die of aging. So it's by far the leading cause of death. Those deaths, as I've sort of explained, are already preceded by this huge amount of suffering. So that's why I think it's our greatest humanitarian challenge and this could, therefore, be a very depressing talk and a very depressing book, but luckily, we can now come to what we might be able to do about it. And I'm sorry, this is the very last time I'm gonna show you the graph (audience laughing) that changed my career. So humans' risk of death doubles about every eight years I already mentioned, but what we can do is look around the animal kingdom and see if we can find any examples of creatures that don't have this same fate. And this is one of my favorite examples. It's a beautiful little freshwater creature called a hydra. It's about a centimeter long. So that's a sort of mildly magnified microscope image of it. And they first came to the attention of science because they've got incredible regenerative capacity. So you can chop basically any bit you like off a hydra and you'll end up with two hydra. You'll end up the first hydra will heal itself and the second bit will turn into a whole new hydra. They've even done experiments where they put a bunch of hydra in a blender and they end up with a load more hydra. (audience laughing) Basically, they've got incredible power. But the other thing that the scientists noticed while they were doing all these slightly crazy regeneration experiments is just how long these guys live. And actually their risk of death with time looks something like this. So their risk of death is about 0.2% per year. And that means if you do the math, so we've not actually done the experiment cause we haven't had long enough to actually test this out. But we think that about 10% of those hydra would still be alive after a thousand years. Now what's more amazing to a scientist than just how long they live is how flat this line is. That line, as far as we know, doesn't change depending on how long ago they were born. And so hydra have a property that we call negligible senescence, so negligible, not much, senescence, just the scientific word for aging. It means that their risk of death doesn't change with time. And that's really incredible because what this shows us is although we may age and our pets may age and so on, aging isn't an iron law of biology. There are animals that literally don't age by this statistical definition. And so the question is how can we become a bit more hydra? How can we perhaps not get all the way to having a 0.2% risk of death per year, but how can we flatten that curve, as was the fashionable thing to say about 12 months ago, and become a little bit more hydra and a little bit closer to negligible senescence? Well, you might be thinking Andrew, come on, this hydra, it's a centimeter long freshwater creature. It's got a handful of cells in it. I'm 37 trillion cells. I'm much more complicated than that. We can't possibly learn anything from those. Well, how about this beautiful creature? The reason that this graces the cover of the hard back version of my book is that this is a Galapagos tortoise. The oldest one recorded we think was about 177 years old. We're a bit uncertain. But it was brought back, we think, by Charles Darwin on his expedition to the Galapagos and it survived Darwin by over a century. But what's more amazing than tortoise's long lifespan is that, again, they're negligibly senescent. It's also sometimes called something which is a little bit more beguiling called biological immortality. It's not real immortality because you can still die, but what happens is that because their risk of death is constant with time, they often die much, much later. So Harriet the tortoise who was the longest ever recorded, she died of a heart attack, but she did so at 177 rather than 77 like a human might. And what's most exciting is when you've got an animal on the scale of a tortoise, you can see whether or not it gets old in the ways that we might understand it. So we now know that tortoises don't get anymore frail as they get older. They even remain fertile until very, very late in their lives. They've got all these different properties that seem to just be entirely maintained. They're in any increased risk of disease. They're still zooming around, well, about as fast as a tortoise does, the same as at age 150 as they were at age 50. So that's an animal that's much, much closer to us, much, much more similar to our biology. And then if you wanna come even closer to humans evolutionarily, this beautiful creature. You might be thinking, Andrew, that's a penis with teeth. (audience laughing) It's actually a creature called a naked mole rat. These things live to about 31 years. That's the longest ever recorded. They do live 25 to 30 years normally. And that's a really incredible age. Although that thing looks very wrinkly, these, too, are negligibly senescent. They don't appear to have an increased risk of death or an increased risk of disease as they get older. They're just born looking like that cause they have to squeeze past each other in tiny little burrows and that saggy skin really helps with that. They also seem to be protected from all kinds of age-related diseases. They're protected from dementia. They're protected from cancer. So they really do seem to, until the very, very last moments of their life, get older without getting old. And these creatures, they're very closely related to mice and mice only live two or three years, even in the lab, perhaps only six months to a year in the wild. So these things live an incredibly long time. They also do that with this negligible senescence property. And what this really shows us is I actually think there are probably loads more negligibly senescent creatures out there. It's just that the ecology and the sort of hard work of going out and tagging all these creatures and coming back maybe 150 years later to see how long they've all lived. It's just really, really tricky science. It's gonna require huge projects that span decades or maybe even centuries. So I think that aging is a far less universal phenomenon than we think based on the fact that a lot of the mammals that we experience in everyday life seem to share this phenomenon. So what's going on in their biology that will allow us to try and slow down our own aging process. All very well finding these animals that do this stuff. Going back to this question of what is aging. I think you can see that on the slide by behind me, I've cheated. And the way in which I've cheated is that every single one of those things is a massive category. Think about cancer. There are hundreds of different kinds of cancer. Think about memory loss. There are so many different processes that could go wrong in your brain that could cause you to lose your memory as you get older. These things are huge, huge categories of stuff. You'd have to really write out what's actually on this slide, it'll be in size one, it'll be bigger than the whole wall of the lecture theater and it would take me a whole evening just to read through all those different things. And the other thing is the way modern medicine approaches these ideas is it treats them very much in silos. So if you get cancer, you might find a lump, you might go to your GP, your GP will send you to an oncologist, a cancer doctor, they'll give you some chemo and radiotherapy. Maybe that cures the cancer, maybe it doesn't. That oncologist will have very little sort of, will pay very little attention to the wider problems that you've got in your body. They won't be worrying about your dementia. They won't be worrying about your sort of slight amount of heart disease. And this has a consequence that we end up fighting these fires, these things that are the ending, sort of the end consequences of the aging process, but we don't attack the problem at its root cause. And just to really illustrate just how significant, how sort of significant our lack of ambition is here. If you were to completely cure cancer, literally, if I was to tell you I've got this injection, no one will ever die of cancer again, it would only add three years to human life expectancy. And the reason is that something else would be waiting in the wings to kill you. By the time you're old enough to have been diagnosed with cancer, you've probably got maybe some heart disease. You might have a bit of dementia on the go. There are loads of other things that could be just hanging in there, waiting to finish you off if the cancer doesn't quite manage it. So as a result, what we need to do is go after the aging process itself. I hope I've convinced you. And that's much more exciting now because if you were to ask an aging biologist what is aging, they might give you a list that looks something like this. Now I don't expect you to read through every single part of this, and you'll be relieved, anyone with families, that I'm not gonna go through every single one of these before you can go home this evening. But what you can see is this is a much shorter list firstly. A lot of these things are categories of sorts, but they're not as sort of expansive as the category that is cancer. And they're also much more fundamental. These are the cellular molecular biological drivers behind aging. You could pick a handful of these and any given age-related disease can be explained by a sort of a little collection of these that go on to cause that disease. And so the idea is that by treating these particular changes that happen in our biology, maybe we can try and reduce the risk of many, perhaps even all of those age-related diseases at the same time. Now in order to try and make that a bit more concrete, as I say, rather than going through the whole list, I'm just gonna pick a couple and explain to you how it is that we could potentially treat these things. What happens as you get older and how it is we could potentially treat them? So I'm gonna start with something that I very often get asked about. When you say you've written a book on aging biology, a lot of people say has that got something to do with telomeres? And the answer is maybe. So, firstly, we're gonna start with what are telomeres. This is a beautiful picture. If we can just take the lights down a bit because there's some beautiful blue there that you can't quite see. That blue is staining of our DNA. They're the chromosomes. So this is where all your genetic information is stored and it's been tagged with a fluorescent dye. That means under the microscope, it glows. So you can just about make those out I think now. And the red and the green bits are the ends of the chromosome. So this is another part called the telomeres. And these are the bits end of your chromosomes. And if we were to zoom in, then it would look something like this. You might know that DNA is made up of four letters, so called base pairs or so called bases I should say. And the telomere is just this incredibly long, repeated sequence. It's just TTAGGG, TTAGGG, TTAGGG. As far as the eye can see, hundreds of thousands of times. You can bring the lights back up, by the way. There's not gonna be any more beautiful microscope pictures now. The question is why has our biology engineered it such that we have this sort of seemingly repeated nonsense on the end of our chromosomes? And the answer is it's to solve a fairly ridiculous biological problem. So when your cells divide, your DNA has a duplicator in order to make sure that both of the daughter cells that are produced from the division have a full copy of your DNA because that DNA is the instruction manual that tells our cells how they work so they sort of need all of it. But when your DNA is copied, you can sort of imagine it like a builder trying to build a wall, but she's standing on the wall that she's building. So she puts down a brick here, then she moves along and puts down a brick here and moves along, puts down a brick here, but when she gets to the end of the wall, she can't place the brick where she's standing. And that means inevitably, there's gonna be, DNA is a double stranded, double helix. There's gonna be a single stranded bit of DNA sort of dangling at the end. And evolution has never come up with a better strategy to replicate our DNA than that because it came up with a kludge to solve the problem. And that kludge is telomeres. Rather than having essential genetic information that you'd be very sorry to lose on the end of your chromosomes, instead, you have this repeated nonsense. And say you lose few tens or hundreds of bases of this TTAGGG repeat sequence, then it's no real hard feelings. It doesn't really have any impact on your biology. And that sort of solves the problem. It papers over the cracks as it were. But as you can imagine, this isn't really a very long term reprieve from this particular problem, because eventually, as you get older, your cells in your body in a lot of places, they're dividing all the time. So if you think about your skin or the lining of your guts, these are pretty sort of nasty environments. You're exposed to the external environment or all the rubbish that you eat. And these cells, therefore, basically they evolved to be disposable and they're replaced by stem cells that divide and then constantly renew the outside of these tissues. They're called renewal tissues. And that means that as you get older, the telomeres of these stem cells get shorter and shorter and shorter and shorter until eventually you essentially run out of telomere. Now that all sounds well and good in terms of the cell biology of it. That's the thing that you can observe in cells in a dish. Their telomeres do get shorter. This does actually matter in full sized human beings. There's always a question you should ask yourself when somebody tells you some results of something in the lab. So let's have a little look at a picture. I love graphs with age along the bottom. This is sort of recurring theme here, but this time, instead of chance of death, we've got the length of your telomeres in bases. So as I say, those chemical letters the DNA is made of, and the graph looks something like this. And that's what we in science call not a great correlation. (audience laughing) You can see that there is a sort of pattern going there, but there are some 20-somethings who have shorter telomeres than some lucky 90-somethings. And you gotta ask, who is this guy? A telomere Wolverine? (audience laughing) It's probably actually an experimental artifact, of course. But what you can see is this isn't the greatest way to determine someone's age. We've already got a technology that can do that rather more accurately. It's called birth certificates. Nonetheless, there is a correlation. And if you draw a line through, you can see that that's the equation. So your telomeres by this unit of measurement start about 5,000 letters long, and then every year or so, they subtract about 17 or 18 of those bases. And so gradually over your lifetime, they go from, eh, quite long to, eh, a little bit shorter. And that's, as I say, a fine correlation, but it's never gonna measure up to birth certificates. However, there is definitely something going on here. And the reason we can say that is we've done experiments looking at people who have longer and shorter telomeres for their age. And if you have short telomeres for your age, it tends to mean that you're predisposed to various different diseases. Think about diabetes and cancer and so on. It also tends to mean that you're more likely to die so there have been these rather morbid studies where you get identical twins. So they've obviously got identical genetics. They were probably brought up in quite a similar environment, but you find that the twin who has the shorter telomeres is more likely to die before the twin who has the longer telomeres. So there's definitely something going on in this biology. And again, you might think this is just me delivering bad news that all of our telomeres are shortening as you listen to me right now. The good news is there is something that we can do about it. And that comes in the form of an enzyme called telomerase. Telomerase is something that exists to extend those TTAGGG repeats. And it's really, really important because if you think about it, when you have a baby, you don't want that baby to be born with stubby, short telomeres from middle aged you. You want to have lovely, long, fresh telomeres. So there are certain scenarios in the body where we activate this gene and extend those telomeres. The question is why doesn't evolution just leave telomerase on all the time? Why, in most of our adult cells, is there no active telomerase? And so therefore, we thought maybe we could just turn this thing on and it would basically be a immortality enzyme. And I remember back when I was at school in the 90s watching a Horizon documentary basically touting telomerase is the solution to our mortality, but of course, scientists hate this sort of hype and particularly when it's got a cynical problem at its core. And that problem is the reason that our bodies don't activate telomerase all the time is cancer. So if you can think about what would happen if our cells could divide indefinitely, well, there's a disease that involves cells dividing indefinitely, and it is, of course, cancer. So by having telomerase activated in all of your cells, that massively increases the risk of cancer. It doesn't cause cancer as such, but it sort of pre-ticks a box on cancer's list cause it means the cells have that capacity to divide indefinitely. And therefore, it's a really bad idea. And this is actually reiterated by doing some mouse experiments. So if you get a mouse and you give it some telomerase, the way that you do that is that you inject some genes into the very early embryo. It's called germline gene editing. So you add an extra copy of telomerase. What happens? Well, the mice basically all get cancer, which it's bad news. And I think also it was really bad news for the idea of telomerase because scientists love to latch onto one of these cynical narratives had this supposed immortality enzyme that got a load of hype, turns out it just causes cancer. Nature's a double edged sword. Isn't that a horrible irony? And the field really sort of collapsed a bit in the early 2000s when these results came out. But thankfully, some scientists did persist. And I think something that's worth thinking about with this is another reason I think scientists were cynical is because you think about evolution. And the reason that you think about evolution in this context is evolution's clearly made that decision to turn off telomerase in as much as evolution decides anything, but let's just skip over that for the moment. It's made that decision because it realizes that the risk of having telomerase activated is higher than the benefit from having it activated. And there's this very well known phrase that evolution is cleverer than you are cause evolution has had millions, maybe even billions of years to optimize the various processes going on inside our cells. And what that means is you as a naive scientist go and stick in some telomerase, well, of course you're gonna mess things up cause evolution's optimized them very carefully. So in 2008, there was a paper published where scientists did something still naive, but slightly less naive, which was they added, they got a mouse and they did another of these germline modifications. They added telomerase, but they also added three other genes, P53 P16, and Arf. I'm not gonna talk about exactly what those do. Basically, these are anti-cancer genes. They're genes that keep an eye on the genome inside the cell. And if there's any problems in the DNA that might predispose that cell to become cancerous, what they do is they shut that cell down. They either convince the cell to commit suicide in the process called apoptosis, or they turn that cell into a non-dividing senescence cell. Hold that thought, we'll be coming back to that in a second. But nonetheless, that puts the brakes on cancer. Either the cell's dead or it stopped dividing so that it can't turn into a tumor. And it turns out that by adding this combination of genes, you actually can extend mouse lifespan by about 40%. And they didn't seem to have any increased risk of cancer compared to a normal mouse. So that's a really incredible result and it sort of blows a hole in the idea that evolution is cleverer than you are. The reason I think is probably that evolution still is clever than you are. It's just optimizing for something that you aren't optimizing for. Evolution is optimizing for reproduction. It wants mice that can churn out as many babies as possible, successfully pass on their genes. But what we might be optimizing for is health or length of life or something like that. And if you want to have something different from what evolution's optimized for, even relatively naive interventions like this seem to have some level of success. So although people might tell you that aging is a really complicated process, we've actually got one up on evolution because evolution didn't optimize for animals necessarily that would live a long time. And then there's also optimistic news for those of us in the audience who have already been born because we don't wanna have a treatment that's only applicable to tiny little embryos. Some scientists are, the same scientists, in fact, gave temporary copies of telomerase and they did this to adult mice. So rather than giving a gene that's always activated, they gave it in a form where it would pop into the cell, turn on the telomerase, lengthen those telomeres for a bit, but then that telomerase gene will get degraded so it would disappear out. And so that extended those mouse telomeres. And again, it gave them 20% longer life and no seeming increased risk of cancer. And this is a treatment that was done in adult mice. It was given to mice that about a year old and obviously, mice age much faster than humans do so that's about sort of 40, sort of early middle age in human years. So there's hope for most of us sat in this audience yet because these treatments can be applied after you're a baby and nonetheless have an effect on your lifespan and have an effect on how healthily you live as well. So I think this really shows it's just a really fascinating story of something that was touted initially as an immortality enzyme, had this sort of obvious cynically exploitable dark side, but now thankfully, has these prospects where telomerase and telomeres may actually be a more exciting prospect when it comes to aging as well. So that's one of the hallmarks. I've show you how telomeres get shorter with time and we can extend them to try and fix them. I thought I'd also mentioned senescent cells and I already brought those up and said that this is something that you should hold that thought and we'll return to. The reason is that senescent cells, these are cells that are aged. We already learned the word senescence in negligible senescence earlier in the talk. These are cells that accumulate in all of our bodies as we get older and their cells that have stopped dividing as I mentioned just now. So their cells that, for various reasons, either they've got a lot of DNA damage or their telomeres have got critically short and the body puts on the breaks. It says to that cell, "You're not gonna divide anymore." And the reason that the body does that, as we've already discussed, is it's an anti-cancer mechanism. And when you're young, that works really well because the senescent cell sends out this whole bunch of signals and it says, "Hey, I'm over here. I'm senescent. Immune system, come and gobble me up." And an obliging immune cell will wander over, gobble up the senescent cell and all as well with the world. The problem is that as you get older, there are more rapid processes producing these senescent cells. Your DNA's got more damage in it. Your telomeres are getting shorter and so on. So the production side is ramping up. At the same time, your immune system is getting weaker because you're aging for a variety of reasons. One of which actually is some of your immune cells going senescent. So there's this sort of vicious circle going on. And so these senescent cells start to accumulate. And the bad news is that sort of cocktail of molecules that the senescent cells are emitting don't just attract only the immune system. They seem to accelerate the whole of the aging process. So unfortunately, as you accumulate these senescent cells, it accelerates your aging in a whole variety of different ways. And actually, ironically, those secreted molecules can even, at high enough concentrations, increase the risk of cancer. So they even sort of go counter to the very purpose evolution originally engineered the cell type for. So that's the bad news. The good news is we have drugs. They're called senolytic drugs, and these are drugs that can go in and kill the senescent cells while leaving the rest of the cells of the body intact. And there are some really exciting mouse results relating to these drugs. So in 2018, there was a paper published where they gave these senolytic drugs to a bunch of mice that were 24 months old now, so again, mice aging faster than us, that's sort of 60, 70 years old in human years. These are quite old mice and it basically made them biologically younger. So the first thing is they lived a bit longer. That's good news. But they didn't just sort of stretch out the frail period at the end of life and have them staggering on unable to summon the energy even to die. They lived healthier as well. They got less cancer, they got less heart disease. It wasn't just diseases. They were less frail. They were able to run further and faster on the tiny little mouse treadmills they use in these experiments. They had improved cognition. So if you put a young mouse in a maze, then what you find is it's very exploratory. It's very excited to explore this new environment. If you put an older mouse in a maze, it's often a bit more anxious, maybe it's just a bit lazy cause it's not quite so physically capable. And by deleting these senescent cells, you actually restored some of that youthful curiosity. And finally, these mice just look fantastic. I'm a computational biologist so I've never been in a biology lab. I don't which end you hold a pipette from. But nonetheless, even to my wildly untrained eye, mice that I've had these senolytic treatments, they look great. They've got thicker, plumper fur. They've got nicer skin. They just look fantastic. They look younger. And so what this really shows us is that these senescent cells, they are a hallmark of aging. They were something that accumulates with time. And by getting rid of them, you can slow down, perhaps even reverse the aging process. And not just a single disease. This isn't like a prevention for a single thing. It seems to be for many, maybe even all aspects of the aging process. So that's a really fascinating thing. And I think something has the potential to be this sort of holy grail to show us how aging treatments should work. You wanna get something that you can give to an older person, you can reverse or change one of those hallmarks back to a younger state and then you can increase their lifespan and their health span, most importantly. So the time they spend in good health in a variety of different ways. You can prevent not just one disease, but maybe even the whole smorgasbord of diseases. And that's why I think this has got the potential to be a revolution on a par with antibiotics. Cause in exactly the same way as a single antibiotic can treat a whole range of bacterial infections, so, too, a single anti-aging drug should be able to prevent, not just treat, but actually prevent a whole range, maybe even all of the symptoms of aging, even the cosmetic stuff. I think it's relatively likely that we'll go after something that's a bit more serious and the patients will come back and say, "Wow, my hair's growing back. This is fantastic." And then you'll get a load of patients going, "Oh, my knee's a bit dodgy, doctor. Can you gimme some of those senolytic drugs please?" Just in order to try and get access to those cosmetic benefits at the same time, because fundamentally all of these things are driven by the same aging process, the same underlying hallmarks. So senolytics are a super cool idea, right? But there's a slight problem to their adoption. And that problem is that currently, they're only being explored for specific diseases where we know that senescent cells are a problem. And the place that that might start is something like there's a disease called idiopathic pulmonary fibrosis, lung fibrosis if you want slightly less of a mouthful. It's where your lung tissue starts to scar. And this often is a very age-related disease and it happens much more commonly in older people. And it's basically irreversible and it's a disease with a very poor prognosis. And we think that senescent cells are involved in this scarring process. And so this is one of the areas that one of the first places where human trials are gonna start. And that's exciting cause hopefully it could give a treatment prospect for people who haven't really got one with this disease currently. But obviously, it's not handing these things out preventatively for the whole aging process. And the first thing we wanna see is some convincing human data for these more specific conditions. We wanna see that they're clearing the senescent cells. We wanna see that they're improving the prognosis of patients with these specific senescent cell associated diseases. But most importantly, we wanna see that the drugs are safe because if you've got IPF, then you are in a position where you've got quite a serious disease. There are no real effective treatments at the moment. So you're willing to take a bit of a punt on what is still frankly a treatment that's been shown to work in mice, but otherwise, it's quite experimental. Whereas would I take a senolytic now? Would I take a senolytic if I'm 60? I'm not really sure. We wanna see a bit more human data and particularly we wanna make sure they're very, very safe and they don't have any serious side effects. And the other problem beyond that is that there's just no way to get it regulatory approval. And that's because the way that medical regulators approve drugs at the moment is they're traditionally approved to something called a specific indication. That's just sort of pharmaceutical regulator jargon for a condition or a disease. And that means you can get a drug approved for treating cancer or for preventing heart disease, but can you get a drug approved that you're gonna use to prevent aging? We're gonna give it to people who are currently, by the medical system, perhaps be classified as healthy and we're gonna use it for some kind of preventative, nebulous thing. Well, there's another drug that's actually blazing the trail for what I think are probably the more exciting drugs like senolytics and it's a totally revolutionary trial of a thoroughly unrevolutionary drug. It's a drug called metformin. This is a drug that actually, some people in here are probably taking. It's certainly a drug that almost all of you will have a friend or a relative who's taking. It's a very, very common diabetes medication. It's one of the most commonly prescribed drugs in the world. There are over 80 million prescriptions a year written in the US. In the UK, we've been prescribing it since the 1950s so it's got this incredibly long safety profile. We know it's a really safe drug. What's quite exciting about Metformin is that we think it might be able to have an effect, not just on diabetes, but on the aging process itself. And this first came out in a study in the last decade or so, where again, we've got time in years this time rather than age along the bottom. So this is the time since the study started and we've got survival up the right-hand side. I'm gonna show you something called a survival curve. And this was a retrospective study looking back at people's NHS medical records. And the sort of the main purpose of the study was to look at the difference between a class of diabetes drug called sulphonylureas. And what you can see is, thankfully, that's a 75 down there at the bottom so not everyone is dead after five years. But you can see that that's the sort of rate at which people were dying. So that's a sulphonylurea treatment. If instead you treat the patients with Metformin, you can see that's a much better survival curve. There are far more people alive at the end of this particular sort of retrospective experiment. So that's a point if you're a diabetic, that's why Metformin is the first line treatment. However, that's what's called a control group. So a group who are sort of acting as a statistical control to understand what's going on with the drug here. They also included some people who were weren't taking Metformin and the reason they weren't taking Metformin is because they were non-diabetic. Now what's interesting about that is that if you're not diabetic, you are often much healthier in a lot of ways than someone who is diabetic. You've probably have a bit less, you're carrying a bit less weight. You've probably got less heart problems. There are various other things that sort of come along with diabetes. And then obviously, you are not taking the Metformin. However, their survival curve looked a bit like this. And what's really interesting is they seem to be dying at a more rapid rate than the diabetics who are taking Metformin. So the question is is this because Metformin has some kind of antiaging effect? Now we've gotta be careful because this is an observational study, as it's called. So we're looking at people out in the world. We're not actually intervening in any way. So the problem is there could be some kind of confounding factor. An example of that is that maybe if you've got diabetes, you just go to your doctor more often. Because you've got diabetes that's being monitored, you pop in. If you get high blood pressure or something else goes wrong with you, you've got a regular visit with your GP scheduled and so they might spot it a bit earlier. So maybe that's one of the reasons that patients on Metformin live longer rather than it being intrinsic to the drug itself. So what we really want, ideally, is a randomized controlled trial. So a drug trial where people are randomized into one group. They're either taking Metformin or not at random, and then we can see if it's the drug itself that's having the effect rather than something else about those individuals. And that's the purpose of the tame trial that was supposed to start actually a few years ago, but COVID, and hopefully, we'll be starting at some point soon in the US. It stands for targeting aging with Metformin. You can see it's an American trial cause they spelt aging wrong, (audience laughing) and the idea behind this trial is they're gonna get 3000 people and they're gonna give half of them Metformin and half of them a placebo, so that's a drug, a pill that basically doesn't do anything, and they're gonna watch them for three to five years. And what's really interesting about this trial is they're not gonna look, they're actually explicitly not looking for whether or not it prevents diabetes, but they're gonna look at whether it prevents a whole range of other age-related issues, things like dementia and cancer and so on. Obviously, whether people die is another really, really good indicator. And if they find that the people who are in the treatment groups, who are getting the Metformin are dying and getting these diseases at are lower rate than people who are in the control groups who aren't getting Metformin, then what they'll hopefully have demonstrated is the Metformin slows down the aging process itself. And this whole trial protocol has been developed in collaboration with the FDA, the Food and Drug Administration in the US who are the regulator of medicines. And what that means is this is a pathway which will allow future medications potentially that are treating aging to sort of follow that same trial design. So they've designed this, this isn't a thing that's normally done. Normally clinical trials are done. Then you take the results to the FDA, but they've developed the protocol in collaboration with them in order to sort of lay this groundwork. That's the reason this trial is revolutionary cause it could open up a whole new class of, ability to regulate and approve drugs. The reason it's not revolutionary is firstly, as I said earlier, Metformin is this really, really widely prescribed drug. Second reason is if we go back to this graph, you can see that the difference between the Metformin and the non-Metformin group is not very much, like maybe six months, could you make that a year if you squint. So we're not expecting that metformin's gonna suddenly make us all immortal. In fact, it might not have any effect on life expectancy. That's the whole point of doing a trial. But the reason it's been chosen is because it's basically a safe pair of hands. We've been prescribing thing for so long. We know it doesn't have any really serious side effects. And I think perhaps one of the most important things that the first trial of a real anti-aging drug can do is not make people grow a third arm or something which is gonna completely destroy the field for 20 years. So the idea is this is a nice, safe option. It probably isn't gonna transform the world, but if it does make a difference or even if it doesn't make a difference, in fact, it's gonna lay the groundwork for those future and potentially more exciting drugs. So that is the tame trial. And if we go back to these hallmarks, I think what's really, really exciting is that we've got so many different ideas. So you see there are 10 things on this list. We've got multiple ideas for treatments that address each of these hallmarks of aging. And that means that even if Metformin doesn't work, even if senolytics don't work, even if telomerase doesn't work. We've got loads and loads of other things. It'll be bafflingly unlucky if literally none of our ideas are successful. And what that means is that we've got loads of opportunities to give people longer, healthier lives. And what I sometimes talk about, if we're gonna think a little bit further into the few future here, I sometimes like to talk about a cure for aging. Now this sort of raises the hackles of some scientists. It is a bit of a bizarre sounding concept, but actually I think this is really what we should be aiming for. Cause all I mean by a cure for aging, this isn't some sort of wacky sci-fi nonsense. It's a risk of death that doesn't change with how long ago we were born. And we've already seen that that's a biological possibility. There are loads of different animals that have negligible senescence property. And although it might not necessarily happen soon, I guess we'll have to see, depends how lucky we get with these various treatments. There's no biological reason it's not possible. And from an ethical standpoint, we'll get into a few more of those questions in a moment, but it just seems completely inarguable. It's still the ultimate goal of modern medicine. We want to try and reduce suffering to the lowest possible level. We want to reduce the instance of all these different diseases. And so this is something that really, really excites me. And when I talk about a cure for aging, I think a lot of people imagine a single miracle pill that's gonna, some lone genius is gonna invent some magic thing and we'll all just pop it and live forever. That isn't what this is gonna look like. Firstly, you won't live forever cause you'll still be able to get hit by buses or get whatever the next pandemic is and that could kill you. And secondly, it's not gonna be a single pill because there are loads and loads of different things going on here. I think we're gonna require treatments for multiple of the hallmarks of aging. Maybe even all of them. There might even be other things that we add to this list. What's kind of exciting is that our first really naive attempts where you just try and add a bit of telomerase or delete senescent cells do seem to have quite wide ranging effects. So there's a little bit of hope that we don't have to understand the whole process. But I feel like once we start to target multiple of these hallmarks, firstly, we're gonna be on a much better path towards developing treatments. And secondly, it'll help us to understand scientifically which of these hallmarks are the most significant and how they're all connected to each other. And I think that's ultimately what we're gonna need if we want to cure aging is to understand sort of the complex ways in which all of these different things are interdependent of one another. So why should we be aiming for it? Well, I hope I've convinced you from the first part of the talk that this is our great humanitarian challenge. It's inarguably the largest cause of death. It's, I would say, almost certainly the world's largest cause of suffering unless you've got some other contenders and every single day that we bring forward a cure for aging, it saves a hundred thousand lives. Now you might not be too worried about your own death, but I think it's, I'm surprised sometimes by how controversial this is, but I do think death is bad and a world in which there was a bit less death would be a better world. So we can argue exactly how long human life expectancy should be. That's a fascinating question, but I think in general, reducing death from the level it's at at the moment would probably be a good thing. And this is a hard goal, right? This is something that's gonna be a real challenge for us to implement. It's gonna require a huge, huge amount of biology. It's gonna require us to uncover all of these, how all these hallmarks work and how they're all connected, but it's not an impossible task cause we've already seen these senolytics. They're already in development. There are 20 or 30 companies now trying to turn senolytics from an idea in the lab into something that actually works in humans. It's not at all inconceivable that the first anti-aging drug could be with us in the next decade. And that means that most people, again, in most countries are gonna live long enough to see the fruition of this work. And if you live long enough to take the first senolytic, then perhaps you'll live long enough to take the next round of anti-aging drugs. And that gives scientists even more time to develop the next more effective round of anti-aging drugs and so on. So if you can keep yourself healthy and alive for as long as possible, this is a really, really cool time scientifically to be a human being. So that's my sort of positive case for why we should do something about aging. The next question is should we cure aging? And I think, as you can probably tell, the answer's unequivocal yes, but I have discovered from talking to audiences that that is not a universally held belief. And actually, it's a long time since I was first confronted with these ideas. I've had basically a decade to really digest and grapple with all of this stuff. But I think when you're confronted with it fresh, it sounds weird, it sounds sci-fi, it sounds a bit kooky. And actually sci-fi has done us a terrible disservice. All of the situations in which immortality has dealt with or longer lives, they're usually dystopias. They're usually billionaires living forever and there's some underclass who are in mortal servitude to them or something. And so it's very easy to think that curing aging might have loads of terrible moral consequences. Now I actually think the moral case is completely watertight and I haven't got time to go into every single nuance of it here, but I'm just gonna go through one example to sort of give a flavor of why I think this is such a powerful case. And that's probably the question I get asked most commonly is what are we gonna do with all the people? Because if people are living longer lives, then they're gonna increase the strain on the planet. We're gonna increased resource use. We've already got problems with climate change and air pollution and all kinds of other stuff. And actually, I should say I'm pretty worried about this too, because when I was contemplating my life at the end of my physics PhD, I nearly became a climate physicist because I thought that might be a way to have a big impact on the world. And eventually, decided actually aging was a more pressing concern that had fewer people working on it. Nonetheless, this is something very close to my heart. So what about overpopulation as people often sort of pose the question and let's have a look at what happened to population in the last, say, 20 years. And this time, I've got a different sort of time, years rather than age. And up the side, we've got how many people there are in the world. In 1999, the population just exceeded 6 billion. I think in 2011, we exceeded seven. We're coming up on 8 billion people now, but obviously, the real question is what's gonna happen in the future? And one of the most sort of popular population projections is made by the UN. This is the UN's medium variant and they predict that by 2050, we're gonna have about 9.7 billion people. So that's the best guess by the United Nations. Other guesses are available, but I'm just gonna run with this one for now. So what would happen if we were to do something about aging? Well, I thought I'm not a demographer. I'm in no way an expert in population modeling, but what I can do is something really, really simple. I can cure aging in 2025, statistically, of course, not in real life. And what that means is that people will stop dying of old age. People will reach a certain age and they'll just die at the same rate as they did every year before that. And if you literally cure aging in 2025, now I'd like to just emphasize, this is ridiculous, right? Because not only is that a ridiculous timescale scientifically to solve this problem, it's also a ridiculous timescale from a sort of economic and social standpoint. We have to roll out these drugs universally in the next sort of two, three, four years. Absolutely crazy. But as a population pessimist, you could sort of see this as the worst case scenario, because this is a sort of ridiculous extreme. And if we cured aging in 2025, population would look something like this. So by 2050, the population would be 11.3 billion. Now that is more, it's almost 2 billion more people. In percentage terms, it's not quite so much more. It's about 16%. Now that's not nothing. I don't want to have to work a little bit it harder in order to solve all of these global problems. But then you gotta think about what's on the other side of the equation. I want to fight climate change. I want to fight all these different forms of pollution and ways in which we're destroying the Earth's natural environment, but I would happily work 16% harder to achieve those goals if it meant that we could suddenly, effectively stop people dying of old age. We could stop the cancer. We could stop the heart disease. We could stop the dementia. I just find that a much, much more compelling argument. And actually, there's something else that we need to consider here. Not only is this a relatively small change, it's also actually smaller than many other changes that we have to think about. So the UN also produce a low and a high variant. And the difference between these is nothing to do with life expectancy. It's really fascinating just how uninterested demographers are in life expectancy. They think it's basically gonna plateau about where we are now, which is a bizarre expectation, but the difference between the low and the high variant is actually larger. It's 19% than the difference between if we literally cured death and if we didn't, sorry, if we cured aging, I should say, not death. And that's just staggering. A small and relatively expectable change in birth rates is gonna have a larger effect than this ridiculous assumption that I've made about people not dying of old age anymore. And obviously, what's really gonna happen is we're gonna develop these treatments more slowly. They won't be rolled out quite so fast. So the problem that we're gonna have to confront is gonna be smaller still. So I really think just on the face of it, it's not gonna be as large a problem as it sounds like it should be. And actually, if you look outside the UN's projections, there are other very serious demography outfits who think we're facing underpopulation crisis. If you are a real all sort of techno future optimist, it could be that a cure for aging saves us from an underpopulation crisis in the second half of the century. So demography is hard basically. And I think the real lesson that this teaches us is that when you're thinking about these questions, I think the most powerful way to answer any ethical objection to aging is to reverse the question, that's to imagine that we live and that let's take the population example again to run with it. Imagine that we lived in a world where aging didn't exist, people were living much, much longer lives. They were living in good health. People still die. They still, as I say, get hit by buses, get infectious diseases. Even young people get cancer just at a much, much lower rate, but we're living much longer, healthier lives. But imagine we were confronting that overpopulation crisis, there was this terrible toll on the environment. We were polluting everything. There was a huge, huge climate change going on. How would you try and address that problem? Well, I think first of all, we should try and reduce our carbon footprint. We should change the food that we eat. We can reduce our land footprint by a huge amount just by switching to a slightly more vegetable-based diet and so on and so on. And if you tried all of those different things and none of them were working, the only thing that you had, I should suggest this is a very sort of last resort option was to kill people, then would you really do it by inventing aging? This decades long process of horrible decline? I think if you absolutely had to kill people, and as I say, last resort, I'd rather do it in a brief, painless way rather than dragging it out over that extended period. And I think if you try and approach any potential objection to treating aging from a moral standpoint, think about people often ask won't dictators live forever? Would you create aging to kill one dictator, but condemn all of their subjects to decades of suffering, perhaps even worse than the dictator's doing already? If people say, "Wouldn't I get bored with my extended life span?" Would you age to death rather than get bored? It's absolutely incredible. And I think by reversing the question, it's absolutely morally repugnant to invent aging. And I think, therefore, it's equally morally repugnant to allow aging to continue to exist to solve some perceived problem with the world. I just think, therefore, there's this huge, compelling, morally watertight case. And this next slide, this is actually really why I wrote the book that I wrote. This is because I think not only is there a huge moral case, which is sort of the driving factor, I wanna make the economic case now. So we're gonna look at the cost of these chronic diseases. So these are diseases that are, as I say, essentially caused by the aging process. This is cost to the United States. It's got some figures that are much easier to get at which I'll explain why in a second. Cancer cost them 280 billion dollars a year. Heart disease costs 200 billion dollars a year. Stroke, 110 billion dollars a year. Dementia, 270 billion dollars a year. This is the total cost to the economy. So it's the healthcare, it's the people having to give up work cause they're ill, it's the people caring for them and that sort of stuff, all combined together. If you add those up in your head, that's getting on for a trillion dollars. And that's just some of the diseases of aging that total cost of the US healthcare system is over 4 trillion dollars. It's an incredible, incredible amount of money. And yet, even though a huge amount of that healthcare expenditure and a huge amount of other economic costs as well are caused by that aging process. This is the budget for the NIA, the National Institute of Aging. And this is the reason I chose the US, by the way, because the US is one of the few countries in the world that even has a research institutes sort of dedicated to funding aging research. That little square isn't just a style feature. It's in proportion to the size of the amount of money that's spent: three and a half billion dollars, which compared to that almost a trillion dollars, almost a thousand billion is just peanuts. And actually, it's even worse than that. Cause there's a running joke in aging biology. The NIA doesn't stand for National Institute on Aging, but for National Institute on Alzheimer's Disease. Because if you break that budget down, then about 2 billion of it goes to NIA's neuroscience division. This is the part of the NIA that basically looks into dementia and then you've got another billion or so on other NIA activities that do a lot of social gerontology about sort of phenomena around getting old from a social perspective and various other biology. And then when you draw down to the bit that's actually on aging biology, actually trying to understand the processes that give rise to this huge, huge cost. It's about 350 million dollars. That's a bit over a dollar per American, even though in America, they spend about $17,000 per person on healthcare. And as I say, a huge amount of that is caused by the aging process. So even just on a raw economic basis, if you think this research has any chance of success at all, then you should be investing far, far more than a dollar per person in trying to do something about it. Actually, if you break down the sort of huge benefits to society, there was a paper that came out last year that tried to look at the benefits, again, to the US, things are often done cause, obviously, they're the world's largest economy I'm fighting out with China, I guess, but for the moment, it's still the world's largest economy, I believe. And what they found was that the benefit to delaying aging by a single year, so sort of keeping people healthy and allowing them to die that single year later was 37 trillion dollars. And that, again, not million, not billion, trillions, that's 12 zeros. That's an incredible amount of money to benefit to all of those people. And as you keep on scaling that up, if you go up to adding 10 years of life, that scaled almost linearly, I think it was 367 billion was the benefit of adding those extra years of life. So there's really huge, huge amounts of money on the table and the money that we save in healthcare, by the way, we could then spend on solving some of those problems like climate change that I and many others worried about. So there's this huge above and beyond the moral case, there's this huge economic one as well. And we just need to massively increase the numbers on the right-hand side of this picture because if we invest in that research, then we can work our way through those hallmarks of aging. We can actually start to develop some treatments. So that is, as I say, why I wrote this book because I realized that this just isn't something that people are very familiar with, whether it's members of the public, I want people to be going out and talking about aging biology in the pub. I want it to be a sort of topic of political social importance, rather than just being this weird kooky bit of science. It's also really important for politicians and policy makers cause obviously those are the people who ultimately hold the purse strings and they're answerable to the public, which is why it's so important that the public understand this as well. But I also wrote this book for scientists and for doctors, cause I worked for about five years as a computational biologist before starting writing this book. And what I found was that even biologists aren't very familiar with this stuff because aging has historically been quite a small field. You end up with this sort of vicious cycle because there aren't very many people who studied aging so there aren't very many professors lecturing in it so there aren't any PhD programs that people can then feed through and become lecturers lecturing it themselves. There's often not even a page in a textbook about this most universal process in biology and a lot of biologists think it's this sort of inevitable process of wear and tear. I'd met people who had great degrees, great PhDs from great universities and I knew more about aging than they did. And that isn't cause I'm some kind of genius. It's just cause I'd read a few books and it meant that I was in advance of whatever they'd learned. My wife is a doctor. And when I first met her, I think she thought I crazy talking about all this wild treating aging stuff. And when doctors go into medical school and have their lectures on aging, it's all about the geriatric side. It's about these patients, they're really complicated because the average 80 year old is taking five different kinds of medications so you've gotta be really careful anything you prescribe to them doesn't interact with their other medications. They all have social problems cause they're living alone. These are all really important things for doctors to know, but it's pretty likely that within her career it's gonna be possible for her to prescribe genuine, actual working anti-aging drugs. And yet she knew very, very little about it. Thankfully, as you can see from my wedding ring, I did eventually convince her, but nonetheless, this is a huge, huge problem because even the nerds don't know about this stuff. So we just have to spread the word, get these ideas out there. So if you wanna do that, you can find out more about the book at ageless.link. I'm sure a lot of you have still got a load of ethical questions cause I really skipped over that in a very rapid fashion. There's also a free chapter on the ethics of aging biology at ageless.link/ethics. There are some videos about it on my YouTube channel and here are some other links about me. Thank you very much. And I think we've got time for a few questions. (audience applauding)

Channel: The Royal Institution

Views: 595,795

Keywords: Ri, Royal Institution, telomeres and aging, ageing science, andrew steele, dr. andrew steele, andrew steele ageless, dr andrew steele ageless, royal institution lecture, telomeres and aging 2022, anti ageing science, telomeres and aging test, live longer, how to live longer, live longer mark, how to live longer and defy aging, how to live longer and feel better, telomeres and aging 2020, andrew steele ageless tips, royal institution lectures youtube

Id: fX9P1xuIJGg

Length: 56min 59sec (3419 seconds)

Published: Thu May 26 2022

Reddit Comments

[u/StoicOptom]

Andrew is such an effective and engaging speaker, really love seeing the niche he is filling for our field

Edit: /u/statto Given that you talked about senolytics, can I please suggest adding your version of the image of the senolytic treated mice to your slides?

Personally I've found that lay people respond well to it and go 'wow'. It really helps emphasise the promise of geroscience, and is perhaps even more effective than merely talking about concepts like 'healthspan' that can be less tangible

[u/Tramagust]

This was a fantastic rundown and perfect to share with the people who didn't pick up the book.

/u/statto did you ever take a look at Romanian gerontology? I know seems like a very odd thing to ask but it was all the rage in the 20th century.

In the mid century, Ana Aslan was this sort of superstar in the field of the age and the jetset crowd were regulars at her Institute of Gerontology and Geriatrics. The institute had a very simple system: inject a procaine cocktail called H3 to allow patients to be subjected to an intense exercise regimen. Of course this is now obsolete but it's interesting to analyze historically.

BTW Nootropics also came out of the Romanian school of gerontology. Corneliu Giurgea created piracetam in the 60s.

[u/ilkamoi]

I tried several times to get my head around that multi-trillion benefit of even small life extension for economy and failed. Could someone explain? It's not GDP is it?

[u/alex4science]

So death chances double every 8 years. Let's take it backward. Longest lived 122 years (100%). Hence at 114 years expectation is 50%, etc, 134-80=34 ~ 50%/2¹⁰ = 0.05%. He said at 36 it is 1/1000. Close (just 2x difference).

Added: that matched due to total number of deaths from dates of births when verification started roughly equals number of currently living.

[u/alex4science]

https://youtu.be/fX9P1xuIJGg?t=827

I wonder if one can accurately point to average life expectancy from the death chances graph only (provided stable demographics).

[u/alex4science]

https://youtu.be/fX9P1xuIJGg?t=1048

"They remain fertile until very late in their lives" that implied they have a live-span, health-span might be same as lifespan or live-span could be much longer, we just have not seen it fully yet.

[u/alex4science]

He mentioned two successful studies on mice : temporary telomerase - +20% lifespan and removing senescent cells - healthier (2018). What is stopping human trials?

https://youtu.be/fX9P1xuIJGg?t=1817