Anti-Aging: Could This Be The Miracle Drug? The Secret To Living Longer. With Expert Andrew Steele

0:00As a 56 year old woman I do believe that I'm way over halfway to the end of my life and you can tell me if that all might change. Imagine we lived in a world where we didn't have ageing. People were living much, much longer, much, much healthier lives. Are you talking about a world where people could live to 90 healthily? As you get older, your risk of cancer, your risk of heart disease, your risk of dementia, all of these diseases, the risk goes up exponentially, just like that risk of death. Ageing is the thing that causes dementia. Ageing also causes cancer. Ageing also causes heart disease.

0:30And so maybe we should be looking to solve this problem before it happens. what does this miracle cure look like how are we going to do this the first thing you've just slightly blown my mind what would be your dream ultimately you know i just i want to help people avoid this suffering as best as possible andrew how close are we do you think we could have an anti-aging drug in the next five or ten years shut up yeah it's sorry i keep telling you to shut up but you're just blowing my mind that's absolutely incredible what are the major things you would say to somebody, if you want to live the longest and healthiest life possible, okay, these are the things I would advise.

1:07So the first thing is...

1:12Welcome, Andrew Steele. Thanks so much. And I am fascinated by this topic because as a 56-year-old woman, I do believe that I'm way over halfway to the end of my life. And you can tell me if I am or not, or what's going to happen in the future, or whether that all might change. um moving forwards but first of all what got you interested in aging a lot of people ask me this and they sort of assume maybe i had some you know terrible experience with an aging parent or something when i was younger aging grandparent it's actually a graph so i started out as a physicist um and so as you can imagine the way that i see the world is a little bit statistical a little bit mathematical and this graph it's a very simple graph but it's just it's really powerful it really spoke to me when i saw it and it's it's a graph of your risk of death depending on how long ago you were born.

1:59So obviously on the bottom, you've got how old you are. And at the side, you've got how likely you are to die. I think all of us know that as you get older, you are more likely to die, but just how much really shocked me. So let's try and put some numbers to it. If you're lucky enough to be born in the rich world, you've got a risk of death of about half a percent that year. So you might be born with congenital abnormality or cancer or something like that. But if you're fortunate enough to make it through that first year, your risk of death goes down and down and down until the age of 10. And current 10-year-olds have an incredible title.

2:26They are the safest humans in the history of our species. They've got a less than one in 10 ,000 chance of not making their 11th birthday. But unfortunately, it's bad news from there on. Exactly. So our risk of death roughly doubles every eight years. So by the time you're my age, I'm 39. My risk of death this year is about one in a thousand. Now, I quite like those odds. Yes, that sounds quite good. Because that means if that were to continue for the rest of my life, I'd live into my 1 ,030s on average. But of course, unfortunately, that isn't what happens. We carry on doubling and doubling and doubling something every eight years.

2:55by 65 it's about one percent per year still all right you'd still live to 165 on average if that continued but unfortunately one percent is now a big enough number that doubling it is really starting to matter yes and if you and i are lucky enough to live into our 90s but unlucky enough that none of the science we're going to talk about today has come to fruition we'll have a chance of death of about one in six that's life and death at the roll of a dice every single year and you know you can look at that as a as a human and you can think well that's terrifying i've got this exponential wall of mortality coming at me or you can look at it as someone just finishing a PhD in physics and you can think wow there's something really fascinating going on here it looks like there's this incredible synchronized increase in the risk of all different kinds of problems you know cancer heart disease dementia frailty obviously the wrinkles the gray hair we all know come along comes along with aging and perhaps if we could understand the processes that cause that huge increase and huge change in all of our bodies then maybe we could slow those changes down and do something about it.

3:51So I decided to switch to biology and find out if that was even possible. Does your physicist brain massively help you come at this from sort of, with a bit of lateral thinking? I think so. And I think you actually find a lot of people who work in longevity science have a physics or a maths or a computer science background. And I think it's because, you know, I found this myself, my wife's a doctor. When I first met her and started talking to her about the idea of medicines to slow down the aging process she thought i was crazy and that's because i think if you're a medic if you're a biologist there's not a single lecture on this in most medical or biology degrees it's not a page in the textbook about aging which is kind of wild when you think about it because it's one of the few like almost universal processes in biology yeah and yet there's nothing taught about it in university and what that means is i think you know medics biologists they're taught very rightly to be extremely skeptical i want my doctor to be super skeptical checking out all the evidence making sure that the treatments they're giving and we are safe, we've got really good clinical trials behind them.

4:47What that can mean is, you know, aging, anti-aging, particularly this phrase, it's got sort of overtones of cosmetics, of snake oil, of quacks, of skin cream. So, you know, trying to sell that idea to people who haven't been taught that it exists is really, really difficult. But if you come at it, you know, perhaps almost naively, actually, as a mathematical or physical scientist, you just look at this correlation, you say, what is going on here? And if we can understand it, can we do something about it. What would your end goal look like? I mean, I want to talk to you about how we're going to get there, but sort of what do you want to happen?

5:22What I really want is just to decrease suffering. So it's, you know, when you start talking about this stuff, I get a lot of questions about immortality and can we live to 200? These are interesting philosophical things. Obviously, you can write sci-fi about them. What I really care about is the fact that as you get older, your risk of cancer, your risk of heart disease, your risk of dementia, all of these diseases, the risk goes up exponentially, just like that risk of death, you know, increasing massively when you get to the age of 60 or 70 or 80. And so if we can understand the processes that cause all of these diseases, we can push those further and further back into the future and we can keep people healthier for longer.

5:57And it's not just the diseases, because I think that's another problem, because our medical system views things through this very sort of disease-centric lens. Maybe you're getting a bit frail, you're starting to lose a bit of muscle, but it's not getting to the point where you could get a medical diagnosis if it gets really bad we call it sarcopenia but if you're just a bit weak and having trouble opening jars and can't get up the stairs anymore then you know might give you a walking stick or give you some assistive stuff around the house and that's great you know we need to do those things to help our older people but wouldn't it be fantastic if we could come up with medicines that could stop people losing that muscle in the first place and that's just that's that's my real end game here i mean what i love is you're 39 and I'm 56 and I'm in three years time I will be 60 and you're talking about 60 70 80 and you know I am that person and these are all concerns that I think about I don't want it to rule my life I I but I am making decisions in my day-to-day life to try and stave off as much as is humanly possible these illnesses are you talking about a world where people could live we were talking about 90 year olds earlier to 90 healthily and then die in their sleep?

7:06Well this is an interesting question this is the sort of gets to the hub of a debate about lifespan versus health span and what I want to do is expand that health span and what people are sometimes a bit more concerned about is this idea of extending lifespan yes and I think the reason for that concern is that you know you imagine if you're going to live to let's say 100 you might spend the last 20 years in a nursing home we don't want to stretch out that period at the end of life at all. And also government let's face at governments and wouldn't be able to afford it. Exactly. You know, we've already got an aging population.

7:31If we're dragging out that period of frailty, people aren't contributing to the economy, they can't stay active, they can't stay working. This could be a big problem. But the thing is, imagine I did stretch out, you know, our lives to 90 and good health. Why would we die in our sleep? Because if you're healthy, what's going to kill you? You know, ultimately, there's this sort of myth, I think, that you can die of old age. It used to be acceptable to write it on a death certificate. And I think sometimes it is still used. I think the queen's death certificate said old age because that was perhaps the most diplomatic thing to put on there rather than ascribe it to a particular cause but actually you know most people die of a thing and that thing be it cancer be it heart disease often slowly you know saps your independence over years sometimes decades you know when you have a heart attack it's often not that you're absolutely fine the day before and suddenly snap you know you have a heart attack and you fall down dead there are years during which your heart is getting less good at pumping your blood vessels getting thinner and thinner, you're getting slower.

8:23This has a huge impact on your day-to-day activities. Whether it's playing with your grandkids, whether it's traveling, whatever it is you want to do, it gets harder because of these changes. And so I think we've got to bust this idea that you can just die peacefully in your sleep. Some people are lucky enough to do that, and obviously I hope that for everybody. But the real thing we need to concentrate on is trying to reduce the suffering from these diseases. Does that mean, I want to know all how we're going to do this in a minute, But do you think reducing how our frailty or improving our health as we get older, surely that would just mean extending our life as well?

8:57I think it would ultimately. And you can sort of see this as a side effect. But actually, you know, this is something we're already phenomenally good at. You know, if you think about, let's time travel back to the 1830s. Life expectancy in that time was 30 or 40 years old. Fascinating. And so we've essentially doubled what it means to be human in the last sort of two centuries. And, you know, obviously there have been big societal changes while that's happened, but the world has not ended. You know, we're still pressing on. And actually, you know, the goal of most modern medicine, if I was talking to you as a cancer researcher, you wouldn't be asking me this question.

9:29You wouldn't be saying, oh, you know, these people are curing of all that cancer. Aren't they going to be bored with all those extra years of healthy life we're giving them? But as soon as you start talking about aging, and this is really common, people put it in a very separate ethical, moral category. And the only real distinction for me between, you know, a cancer drug or an aging drug is that the aging drug has the power to be much more effective. Because it wouldn't just hit the cancer, it would also hit the heart disease, it would also hit the dementia, it would also hit the frailty. And most importantly, it will be a preventative medicine so it'll stop you getting ill in the first place.

9:58And so for all those reasons, I'm really excited about it. But I think for all those reasons as well, people do treat it somehow slightly differently to the rest of modern medicine. You've just slightly blown my mind. Wonderful. Yeah, I love this. I really hope you're enjoying this episode. And if you can, give us a follow. I'm interested. You know, what you said, I suppose as a menopausal woman, I think this is fascinating because the argument for HRT for me has always been, look, 200 years ago, you wouldn't live past 40. You'd never hit the menopause. So you wouldn't go through this thing where you stop being of childbearing age and then have to deal with the estrogen, why wouldn't you take something that would help you feel better?

10:44I mean, in a way, this is kind of, in a very small way, a tiny way of making somebody feel absolutely fantastic for 10, 20, 30 more years than they would have done normally. You know, my joints aren't aching. Estrogen is WD-40 for the whole body for a woman. my blood vessels are softer I'm thinking that there is new science coming out in terms of Alzheimer's risk and issues so I sorry I mean that's a very long answer and I am going to ask you a question in a minute but that's really blown my mind I think I guess the next question would be what does this miracle cure look like how are we going to do this I'm actually going to rewind back a bit and just mention something that you said which is that most women back in the day and this you know men as well wouldn't have made it past 40.

11:36This is a bit of a misconception about life expectancy. So there are two things that saying the life expectancy was 35 in the UK in 1800 gets slightly wrong. The first thing is that actually a huge amount of the death that happened in that time was in very very either early childhood or the teenage years. So you had roughly a 50-50 chance of making it to the age of 20 and what that meant was that you're dragging life expectancy down an awful lot because life expectancy is just the average amount of time that somebody in that year lived and so the first thing that saying life expectancy was 40 does is it masks this terrible toll of infant mortality but the second weird thing about that and this is actually a really fascinating thing about menopause is that actually you know if you did make it to 20 you probably had 40 50 years of life expectancy left right which means living into your 60s your 70s maybe you would have seen the odd 90 year old in the 1800s there wouldn't have been many of them but they were about and so this sort of headline life expectancy statistic masks that and then that leads to this really fascinating question about menopause like why do women die such a long time after their reproductive lifespan this is almost unique in the animal kingdom so human females undergo menopause we think that certain species of whale orcas killer whales people might have heard of undergo menopause um giraffes there's a couple of other species we have a little bit of evidence for but mostly animals experience a gradual decline in fertility throughout life they don't experience this sudden sort of dropping off a cliff at a particular age and so there's this really fascinating just evolutionary question why do human women and it is just why do we still exist after the most important thing that wasn't quite and be a grandparent.

13:24Yes. And I actually think we have a very important role in doing that. Even if you thought back to cavemen and women, as an elder woman, you have the wiseness, the experience. I feel like that is Amara. Yeah, this is called the grandmother hypothesis. You might have heard of it. No. And so the idea is that maybe one of the reasons that older women stick around post-reproductively, maybe one of the reasons this reproduction falls off a cliff, is because of the wisdom they can give to the later generations. And actually, there are some really fascinating studies in killer whales where they've looked at these pods of whales.

13:56They're swimming around. They've often got this older matriarch. And because she's been around for decades and decades and decades, she knows where all the food is. And so if there's a bad season and food over here isn't able to be found, she'll know the other place in the ocean where you can get some fresh fish. And what they've noticed is that there's actually a survival penalty that's paid. If that matriarch dies, then those pods are less successful in the years that follow. and you know it's the same probably with human grandmas they're able to care for the kids they're able to you know help the mothers help the fathers help around you know the village or whatever it might have been um i think that from an evolutionary point of view if you run through the maths doesn't explain everything about you know why women go through menopause but it's certainly a pretty compelling argument as to you know one reason and the other one is probably just your child bearing a child is is very very hard work as you know anyone who's been through it can attest it's not just about whether your ovaries can produce eggs it's also about the resilience of every other system in your body in order to you know carry that baby to term and then obviously giving birth is um I gather quite a lot of fun as well I actually loved giving birth did you yeah I mean obviously it's intense it's really intense but I I feel kind of sorry for men in a way because that experience of pushing out a being and then them crying and you looking at them and the wonder and the magic of that is beyond like belief you you it's incredible I can totally believe that my wife's actually pregnant at the moment and it's a it's a strange strange thing because she's got this this human growing inside of her and I can see it moving and I can feel it moving.

15:37But at the same time, I am that much more distant from it. And, you know, at the moment, it's still not quite real to me in some ways because, you know, obviously I know it's coming. I understand the biology going on here. But, you know, it's not going to be very many months now before we have a little tiny human being to care for. And that's going to be absolutely transformative. So it really is an incredible experience. But at the same time, you know, I wouldn't want my wife going through this at 90. So maybe evolution's calculus. I mean, would sort of staying on this theme a little bit, if we did elongate health and prevent aging, then would that mean that women evolutionarily would continue kind of that they would continue childbearing until later?

16:19Would that happen? This is a question. It's a fascinating question. Actually, I think the best way to answer this is to talk about one of the potential therapies, which is actually being tried in this exact context right now. Is it? Yes. Shut up. I think this is a really, and it's a really interesting case in point, because one of the challenges with testing an anti-aging medicine is that imagine it slows down aging by, let's say, 10%. Let's pick a random number out of the air. And you're going to do this study. It's going to be years before you can pick up that those people are living 10 % longer, they're getting cancer 10 % later, whatever it might be.

16:49So what we need to do is try and find what are called indications in the medical jargon. So basically stuff that we can measure over a shorter timescale. and a really interesting example of this is the menopause because the female ovary for whatever reason ages much much faster than any other organ system in your body like if you look at the liver or the lungs or the brain they don't all change exactly the same time and it varies from person to person but mostly everything's basically fine till you're 60 then start sort of going downhill a little bit and you know increasing rapidly as time goes on whereas the ovary ages maybe two and a half times faster depending on how you define it and obviously you know a lot of women have stopped menstruating in their early 40s and perhaps into their mid 50s.

17:29So that is an incredible, you know, model system is how scientists would look at this. It's a fascinating example of saying that age is much more quickly. So maybe we can do the experiment much more quickly. And there's a trial called Vibrant at Columbia University, where they're giving women a drug called rapamycin. We can talk a bit about that in a minute. And the idea is they're giving it to women who are perhaps going into slightly early, you know, that their periods are getting a bit less regular, just to see if they can extend that window of fertility. And this isn't, of course, just about fertility exactly as you said you know when you lose your hormones from your ovaries um you get thinner bones you get less muscle mass there are loads of changes that happen in your body that come alongside that and so although you know whether or not you're having a period whether or not you can get pregnant is a really easy to sort of short-term end point the hope is that by slowing down aging maybe with a drug like rapamycin we can then um you know keep women healthier for longer as well as giving them a longer window of opportunity to reproduce and And would giving women oestrogen, even though they can't, would it make sense that I'm not asking because I'm just interested out of HRT and I don't have a hidden agenda that women should take HRT.

18:30But does it make sense that replacing women's oestrogen would help them live longer? It's an interesting question. And there are we haven't got the perfect study, unfortunately, as we often haven't in ageing. But we have got some suggestive evidence that sort of points us in that direction. So for example, if you look back in medical records, women who've had, and I actually call it hormone therapy. I've got a scientist I love called Jennifer Garrison who's trying to get rid of this word replacement because she thinks it implies a sort of deficiency in women. And actually - Oh my God, I love that.

18:58Yeah, I was - What's her name? Jennifer Garrison. Big up Jennifer Garrison. Yeah, she's great. She's absolutely fantastic. Really crusading on this, all this sort of women's health stuff. Yeah, hormone therapy. Yeah, and the other thing that she, if we're going to talk in a manclature, she doesn't like calling the ovaries reproductive organs either because they do so much more because they're in this constant conversation with you know all parts of the rest of your body all these hormones they're giving off exactly your body this huge number of different functions women who have their menopause later tend to live longer and it's not a huge effect the sort of spread of ages of menopause is 10 15 years and the extra life expectancy you get is maybe two or three years if you're at the very latest end of that this isn't you know if any women are watching listening to this who've had early menopause this doesn't mean you're going to die it's a statistical thing.

19:37But, you know, there is clearly some kind of effect going on there. We also know, and there's this fascinating experiment published in 2020 in mice, and they sometimes do slightly strange things in mice. So, you know, forgive the weirdness of this experiment, but they took some ovaries from young mice and transplanted them into older mice. And they found that it made the mice live longer. So these older mice are somehow being given a new lease of life by the hormones that are being provided. And, you know, whatever other interactions those ovaries are doing inside the body. And the strangest thing, and we do not have an explanation for this, is that if they first removed the egg cells from those ovaries, then transplanted the young ovaries without eggs into an older mouse, the mice lived even longer still.

20:15They lived 36 % longer than mice that hadn't been given these transplanted ovaries. So it's not working ovaries, it's just ovaries producing oestrogen? It depends what you mean by working. So the hypothesis, and again, this is completely speculative. We don't know if this is how it works yet. But the hypothesis is that maybe the cycling, when those eggs are present, wears the ovaries out essentially. And so if they're still able to do all the cool non-reproductive stuff that they do they can maintain mouse health and you know carry on keep those mice healthier for longer and therefore living longer without necessarily needing to cycle and produce an egg once a month or whatever that might be i don't understand like when do you sleep i mean you've got so much information at your fingertips and so many realizations to be had and to do um you were talking about the drug that was given um to the women um who were going to try and stay of baby making age or stay fertile for longer what tell me about that drug i'm going to talk to you about it in a minute it's called rapamycin yeah it's a fascinating story behind rapamycin um it was discovered first in the soil of easter island which is the island with the massive stone heads and in the polynesian that's called rapanui so that's where the drug gets its name and um it was first discovered during this canadian expedition because the Chilean government were going to build an airport on the island.

21:27It's 2 ,000 miles into the Pacific Ocean. It's been this isolated human habitat for hundreds and hundreds of years. So this expedition went and took all these samples before the airport came and disturbed this pristine habitat. And in one of the soil samples, they found a particular kind of bacteria. And those bacteria, for some reason, fungi couldn't grow on the plate near the bacteria. So the scientists were scratching their heads, well, you know, these bacteria must have some kind of antifungal agent. And they isolated this molecule, it's called repamycin. and it turns out it has a lot more uses so it doesn't just stop fungal cells from growing it actually stops most kinds of complex cells from growing so the obvious thing that you could do with this and there's a guy called surin sagal who's the scientist who discovered this he thought this could be a cancer therapy because obviously cancer is cells that grow out of control so if you can stop the cells growing potentially a way to treat cancer but he spent about a decade trying to make this work and basically couldn't his drug company shuttered the whole program he ended up taking the bacteria home, hiding them in a freezer, in an ice cream tub.

22:24He wrote, do not eat on this tub. And then when his lab moved from Canada to the US, he sellotaped the freezer shut and smuggled this across the Canadian US border. And eventually, after another 10 years, managed to convince the drug company to restart the program. And this drug has already saved millions of lives because it is indeed a cancer therapy for certain kinds of cancer. It also works as an immune suppressant because it stops the cells in the immune system dividing. If you have an organ transplant to stop your immune system attacking and rejecting that organ they use rapamycin for that um and it's also used as a coating for stents so if you've got one of these little things that you put in your heart to expand the blood vessels they coat it with rapamycin to keep that blood vessel nice and wide open after the stent's been inserted but then in 2009 this result came out showing that it actually extends the lifespan of mice so it can extend the lifespan of mice by about 25 percent if you give it in the right dose 25 percent yes and what's really cool about it is again we're not dragging out that sort of ill period at the end of life it seems to rejuvenate them in loads of different ways it's probably the best studied anti-aging drug we've tried it in loads of different mice you know so we tried it when they're actually tried it in middle age so you're saying you're coming up to 60 these mice are actually about 60 in human years they were 20 months old when they were first given this drug um and this was actually an experimental mistake fascinatingly enough they tried to give it to the mice when they were young but they gave it to them in their food and it wasn't making it into their blood so they reformulated the drug took them about two years to do it and actually the scientists were like well there's no point doing the experiment now because if we slow down aging a bit but we do it at the very end of life we probably won't see an effect but we've got the mice you've got the drug let's give it a go and what they found was even if you give it very very late it has this incredible effect and we found if you give it to young mice if you give it to old mice if you give it continuously if you give it intermittently it seems to have this incredible rejuvenative power on the mice it makes them live longer makes them live healthier we've actually got some preliminary data now in marmosets which are primates they're like much more closely related to us that shows that rapamycin works in them as well so we just need to find out if this stuff works in people so when would that happen well she says exactly taking notes what we really need actually um is just to fund a clinical trial and this is the very frustrating thing because rapamycin was discovered way back in the 1970s nobody has the patent for it anymore and that means it's not in a drug company's interest to run that trial because no one's going to make any money we find out rapamycin is this elixir of youth, then unfortunately, nobody can make any money off the patent because it doesn't exist anymore.

24:44So what we need to do is get together, you know, some probably some public funded or some philanthropically funded scientists, and just run this trial and see what happens. So I think the best advice I can give in terms of trying to find these anti-aging drugs isn't to run out and read all the literature. We haven't got an anti-aging drug that we've proved works in humans yet, but it's to sort of campaign for more funding for the trials, I think is the most important thing. Andrew how close are we do you think? I think where potentially we could have an anti-aging drug in the next five or ten years if we can just do the trials because we've got you know I've talked about rapamycin but we've got dozens of ideas to slow down and reverse aging in mice in cells in a dish in worms in flies and all these things that we do in the lab and it would be mind-boggling to me if none of these translate into humans because you know obviously there are difficulties mice aren't just tiny people they've got loads of differences in their biology drugs don't always translate but it would be absolutely incredible if none of these you know so so many different ideas that we've got in the lab could translate into human beings and so we just need to try a few of these things I think.

25:46What are the next steps then because you're talking about that drug but you said that there are loads of others being developed what do you know of? So I think the best way to think about this in my book I break it down into 10 what are called hallmarks of the aging process different scientists have slightly different numbers we fight about this at conferences but we're all basically talking about the same thing and these are the fundamental cellular and molecular processes that drive aging and this is driving every aspect of aging by the way so you know it's the wrinkles the gray hair the cancer the dementia we know that they're all caused by different sort of quantities of these hallmarks acting together and so let's you know talk about what some of those things are to make it a bit less abstract you start at the very very small level things like damage and mutations to our dna yeah the genetic code that's inside every one of our cells and if there are mistakes in that genetic code, then the cells can start behaving in a way that they shouldn't behave.

26:34And, you know, the most famous example of that is cancer. If you accumulate enough mutations in a particular cell, then that cell can lose the ability to detect when it should stop dividing, and it can just carry on growing and growing and growing and turn into a tumour. Then we could sort of zoom out a bit further, and we could say stuff's happening inside the cells that's going wrong. You can get dysfunction in the cells. So you can get something called a senescent cell, and senescent is just the biological word for old. So these are cells that have accumulated in your body as you get older.

26:59they've either divided too many times maybe they've got some damage to their dna maybe they're just stressed because that i'm not talking about stress in the sort of you know everyday sense but chemically biochemically stressed inside an older body then these cells build up as we get older and we also have a problem that as we get older our immune system gets less good at clearing them away because our immune system's aging at the same time and so that means that these build up and build up and build up and we can see that they drive a whole range of age-related problems and then if we zoom out further actually i've already mentioned one of the other hallmarks of aging is the aging of the immune system because we know as you get older you get increased inflammation this is kind of a low-level paranoia of our immune system i've got to say inflammation is such a buzzword isn't it at the moment everybody's paranoid about sugar spikes and um you know and i know as a menopausal woman inflammation we we don't process sugar as well yeah inflammation is a dreaded it's really tricky because you see you know when inflammation has a very specific scientific meaning it's a phrase that means so acute inflammation is a good thing so we mustn't think that all inflammation is bad if you get a bacterial infection or a viral infection or you cut yourself you need your immune system to rush to the site of the problem sort it out that is acute inflammation and as long as it dies off again after the problem has been solved that's great news the problem is that as we get older it starts to build up and build up and build up and i think inflammation is one of those words that's been um you know if you see it on social media it can sometimes be a bit of a red flag and it really frustrates me because another red flag is a word like holistic so i am all about holistic medicine in the sense that um you know we know that these hallmarks of aging affect every system in your body it's important to understand that the aging body isn't one thing going wrong it's a collection of you know processes all interacting with each other we've already seen you know the immune system ages which means it gets less good at clearing these senescent cells so that's a connection there there are loads of connections between the hallmarks of aging so holistic is the way to think about this thing but if you see someone talking about holistic medicine on social media that immediately sets off alarm bells in my head they're not what their writing might not necessarily be true you know that it's often the sort of thing that either quack doctors say or influences who haven't got medical qualifications and it's really frustrating because these are often like perfectly legitimate words like inflammation is a really important concept might even be one of the most important aspects of aging but if you see someone talking about you know some supplement that can reduce your inflammation that's where we start straying into the slightly pseudosciencey and you know do you want to reduce your inflammation because obviously obviously you do in general you want to reduce the sort of bad chronic stuff that increases as we age but i want my immune system to be standing guard ready to do it's acute inflammation if we need to so we've got to be very careful the immune system is a really complicated system we want to try and make it optimal perhaps rather than you know just just trying to tamp it down all the time i think what's what's interesting with all the information that we get and you're right from people that potentially aren't qualified or aren't experts and they pick up on buzzwords and they use that for clicks what happens is that we end up super paranoid about all the different things in our body that can go wrong and then that causes stress which causes inflammation you know and in fact we're doing ourselves a disservice when you talk about a holistic medicine is it like a thing that will stop all the things or protect all the things how does it work so it might not be all the things but it might be a significant subset of them i think actually the best example i've mentioned these senescent cells we have drugs that can remove these senescent cells but leave the rest of the cells of the body intact and there was a trial that came out in 2018 and they gave mice this combination of drugs it was a cocktail of disatinib which is a chemotherapy drug but it was given at much lower doses than you normally give in chemo and also one called quercetin which is a flavonol it's found in fruit and veg it's uh it's sometimes sold as a supplement and they found actually just by dripping these things on cells in a dish they were very effective at killing the senescent cells but leaving the rest of the cells you know alive basically and they gave this combination to mice and it basically made the mice biologically younger so they waited until they were 24 months old which is maybe 70 years old in human these are old mice yeah and it made them live a bit longer so they weren't just dragging out that period of frailty at the end of life they were actually living healthier as well uh they had less cancer they had less heart problems they had fewer cataracts the clouding of the lenses of their eyes um the mice had less frailty and the way they measured this they basically send the mice to the gym so they have tiny little mouse-sized treadmills in these experiments and the mice that had the drugs could run further and faster on these little treadmills than the mice that hadn't um they reversed some of their cognitive aging so if you put a mouse in a maze a young mouse is really keen to explore to find the cheese whatever mice do in maze I'm a physicist and a computational biologist never worked for mice in the lab but these mice zoom around trying to find stuff if you put an older mouse into a maze they're often a bit more anxious don't really want to explore and they found that by removing these senescent cells they actually reinvigorated some of that youthful curiosity and honestly these mice they just look great like you do not need to be I've actually seen a picture on something on your page I think of the mouse that's kind of old and a bit like losing its fur or its fur's gone a bit kind of scruffy and then the other one's so spelt and bigger.

32:06Yeah, yeah, yeah. I definitely recommend people go and find some images of these mice online that have had this analytic drugs. It's quite sobering. It's surprising. And what this really shows us, and this is, you know, to come back to your question about holistic medicine, these senescent cells, they don't just cause cancer. They don't just cause heart disease. They don't just cause frailty. They don't just cause cognitive decline. They don't just cause the sort of cosmetic stuff, the wrinkles, the gray hair. They are at least a factor in maybe all of those things, maybe even the entire aging process.

32:34So that is holistic. So that does seem like a holistic treatment. So if that research happened in 2018, and you know this to be true, this is fact, is it really because of the patent thing and that pharma companies can't make that enormous amount of money out of the patent, that it's not going further? Surely, as a matter for the world, governments, this should be something we should be looking at. You're really talking my language. This is exactly the sort of thing that I would say. I think, you know, governments need to step up here. To give an example, in the US, they have a National Institute for Aging, NIA.

33:12But there's this running joke in aging biology that actually stands for National Institute on Alzheimer's Disease. Because about two thirds of the funding goes toward dementia. Now, dementia research is hugely important. Please do not get me wrong. But aging is the thing that causes that dementia. Aging also causes cancer. Aging also causes heart disease. and so maybe we should be looking sort of upstream and trying to solve this problem before it happens and the National Institute for Aging does have an aging biology division that gets about$1.30 per American per year compared to almost$20 ,000 per American is spent on the healthcare system so you know even if you're just looking at this from a purely economic point of view a huge amount of that healthcare spend is going on treating the chronic slow diseases of aging as cancer treatments it's dementia treatments and so on it's you know caring for people who've got these diseases there's obviously a wider economic impact as well because people have to give up work they have to care for their relatives you know and also outside the economic stuff it's just rubbish so i'd happily put more than a dollar per person toward that and actually i think in a lot of countries like the uk like the rest of europe those numbers are very hard to find because we don't have a national institute for aging in most of those countries and they're probably even lower i mean it is a thing for the economy, surely, because like you said, the aging population, it's only getting bigger.

34:29We were talking about we don't want to spend 20 years. We don't want to just get older and not get fitter. We don't want to spend 20 years in a home. There's so much at stake here. But it was interesting because, you know, when I first heard about you and like read your book, I was like, I don't, oh, I don't know if I want to live older. I don't know if I want to, even if I was healthier, Would I get bored? Do I want to work till I'm 80 or 90? But listening to you talk, I suppose meeting you in true life, as it were, it is food for thought, isn't it? Because not looking after aging parents, I think looking after aging parents when you hit midlife and you're hitting menopause and you're hitting, it's so hard because you also are hitting a time when you could be, well, you could begin again, right?

35:18Like it's a time to be reborn. And yet you're struck with all these other issues. What would be your dream for your future? I just want to be as healthy as possible for as long as possible. And I want my friends and family and actually everyone around the world. Ultimately, I just want to help people avoid this suffering as best as possible. Because I think that health is just the most important thing. and I think that preserving that health is going to have this enormous wide-ranging benefit you know when you think about you know would I want to live longer because I'd be bored I think you know if my friends are alive if they're happy and healthy I can still travel I can still get out and see them you know we can still go down to the pub whatever you know whatever it is you enjoy why would I get bored like there are more films and you know books to read and then I can possibly do in my lifetime and there are only more and more being produced a slightly um slightly ridiculous example I sometimes like to give is there are 200 countries in the world almost depending on how you count them and that means if I were to visit two countries a year yeah I probably couldn't manage all 200 of them and I bet there's more than one interesting thing per country yes and I know that's a bit of a ridiculous thing to say but it just sort of puts in context there's so much stuff out there in the world to experience and I think this partly is you know comes from a place of privilege I've got a fantastic job I love learning this is you know a great thing but I think as society you know as we're getting richer as people are being you know lifted out of poverty and if we can keep people healthier for longer that obviously feeds back in a positive way as well my vision is just a world where people are healthier for as long as possible i mean i suppose at some point people have to die what are they what's death going to look like what it will probably look like is the same way that death in young adults looks at the moment so it's not as though 30 year olds never get cancer obviously it's thankfully much much rarer but it's not as though it never happens because sometimes you'll get that combination of mutations etc etc you know we can still have infectious diseases you can still get hit by a bus there's nothing that all this aging stuff is going to do to help with that so there will still be you know it's not as though you're going to live forever um but it just means that hopefully fewer people will have to suffer this sort of 10 20 30 years of slow degeneration at the end of life you just said something that really hit hard about the people dying because i think that was one of the saddest things my my granny who brought me up so she was like a mum to me really she um died at 98 but you know all of her friends had gone um and she was lonely and I and I did think that's so sad and in fact my my mum um my step-mom but I call her my mum um she's 75 and she's got that a little bit now that you know friends get in um poor health and everything and I suppose it would be a gift to people to have a wider social circle quality of life we know that connection is so important I feel like um people like you said you know when you talk about aging you're thinking about plastic surgery or botox or fillers and everybody kind of slightly pooh poohs that and like you know it's not like I haven't tried a bit of botox here because I didn't want to frown anymore and like you know I fall I fall prey of that as well because um we want to stay kind of I try and stay as healthy as I can for as long as I can but I am getting older and I can feel it but you're right that the word aging comes with a kind of like you shouldn't try and sort of age longer stay alive longer or stay young for longer it's there's something wrong with that aging is a natural process what would you say to them yeah and i think that one of the um one of the really common thoughts you get back is isn't this just for vain billionaires yes who want to you know they've got all the money in the world and they need time to spend it you know they've got all the money but they haven't got all the time um and i think you know my question in response to that would be what is vain about not wanting to get alzheimer's disease what is vain about not wanting to get cancer i think none of us would wish it upon other people none of us really want it for ourselves i think that this this word aging it's it's actually a really problematic word i think it is as a from a scientific point of view it is the shortest way to describe the process that i'm talking about because the single biggest predictor of your risk of heart disease or your risk of heart attack is how old you are so for example if you have high blood pressure it roughly doubles your risk of heart disease if you're 80 rather than 40 it multiplies your risk by 10 now to call that aging i think is entirely accurate but the problem is you know aging is firstly it's just the passage of time so you know we can't stop aging in the sense that you're still going to have more candles on your birthday cake even if you live to 150 you're still aging in some some sense like you know calendar years are still passing um and we also have you know the accumulation of wisdom the fact that you're watching you know your family grow up you're watching your grandchildren your great-grandchildren whatever it might be great great-grandchildren you know this this is social progress is happening all all kinds of things happen that are aging that aren't bad and we somehow got to tease out this and you also you know you don't want to make this too depressing because actually you know the the real flip side of our aging society narrative is that we are living longer healthier lives than ever before when i do talks on this i love to do a quiz um i get everyone to stand up and i ask them to sit down when they think i've put the number for global life expectancy up on my slides and I have not yet had an audience get this right I've done this in with you know senior academics I've done it with all kinds of people everybody gets this wrong so if you're you know listening or watching at home just think now what do you think global life expectancy is I won't put you on the spot this is but this is the average you know life expectancy in every country around the world and you've pulled them all together so you pull them all together not just the rich countries not just the poor countries all of them together the answer is 72.6 years.