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Can we live forever?
Professor Brian Cox and our expert panel explore ageing, longevity and the science behind our lifespans.
Human life expectancy has increased steadily over the last 200 years, but we might be reaching a ceiling. Is this our biological limit, or could the next big scientific breakthrough push it even further? Could repurposing existing drugs help extend our lifespans?
Our panel of researchers answers audience questions about the societal impacts of longer lives, our cellular ticking clock, and whether we can learn anything from the 400-year-old sharks of the North Atlantic.
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A Question of Science is a podcast series of panel discussions where experts from different fields respond to your questions, sharing the scientific perspective on society’s most pressing questions. A Question of Science is BBC Studios production for the Francis Crick Institute.
Brian Cox: Hello, I'm Brian Cox, and this is "A Question of Science" here at the Francis Crick Institute. Now, I sat down to write this introduction to the first episode, and there will be at least 12 episodes, by the way, and I hope many more. And began by listing the subjects we're going to cover. Why do we age? What is the state of the art in our understanding and treatment of cancer? Should we be worried or excited about AI? Actually, what is AI? How do we ensure that in areas that have become contentious, climate science, for example, we use the best scientific advice to address the problem effectively. And I realised that these are conversations about pretty much everything that affects us today and everything that will shape our future as individuals, as a society, and as a civilisation.
So the aim of these podcasts is to talk about everything, but the twist, perhaps unusually, is we'll talk about everything with a panel who actually know what they're talking about. And I'd like to say something about why I think discussions like this, so scientists explaining what they do, taking questions from everyone, are important. We live in a society that is underpinned by science, and our understanding of nature and the technologies that rely on that understanding are becoming ever more powerful. If access to the ever-growing library of scientific knowledge becomes restricted to fewer and fewer citizens, perhaps because it feels too difficult or too daunting, then, as one of my personal heroes, Carl Sagan, once put it, "Who makes the decisions about the science and technologies that are going to determine what kind of future our children live in?" It should, of course, be all of us, but that requires us to have access to that knowledge.
So our goal here is to throw open the doors of the library and answer as many of your questions as we can about as many subjects as possible. Now, today we're talking about ageing. Are we on the brink of an ageing revolution? Can we turn back time and halt the ravages of old age? But before we dive into that topic, I'm joined by Sir Paul Nurse, the founding director of the Crick Institute. And I wanted to just, Paul, give you a chance to explain why you felt that these podcasts were necessary.
Paul Nurse: I think it's really important, Brian. As you said, science is really at the centre of everything, all the problems and all the opportunities that we have as a society. But we need to be able to discuss those issues in a very honest and straightforward way. And as you say, based on a proper knowledge base of what needs to be considered. And sometimes we get a bit gloomy when we talk about science 'cause we're always looking at what could go wrong, you know, where might it go? And these sorts of things sort of drag us down a bit.
I think we need to consider those things, but actually we should also be optimistic about what science can bring to society. How can science enhance our lives, improve our standards of living, do all the things that we really care about? So I see it as an optimistic series, as well as a knowledgeable series.
Brian: And this leads in beautifully to the subject 'cause the question we're asking, the title of today's podcast, is Can We Live Forever? I suppose one of the questions is whether that is an optimistic or a pessimistic thing to do.
Paul: The first question, Brian.
Brian: It is. Ageing is one of the few things that is a universal experience for all of us. While some people enjoy relatively good health well into their old age, others will experience an extended period of uncomfortable decline as they struggle with poor physical health and cognitive health. What if decline with the growing years isn't inevitable? So, our panel today is made up of scientists who are unravelling the mysteries of ourselves, exploring the underlying mechanisms behind ageing, and developing potential interventions for healthier long lives. So is there a maximum age limit for humans? And as we said, even if we could live for centuries, is that desirable? What might be the societal and medical implications of living longer? Joining us to help answer these questions are our panel, and they are.
Lynne Cox: Hi, my name's Lynne Cox. I'm a biochemist at the University of Oxford, and I've been working on ageing for the past 29 years, looking at the basic underlying biology of how we age. And I'm also running a global programme looking at how to do it better, so-called dynamic resilience.
Paul: Well, as you've heard, my name's Paul Nurse, and I'm director of the Francis Crick Institute, in which you are sitting this afternoon. I know nothing about ageing, so I'm just here as, well, what should I say exactly? But I'm going to hopefully ask good questions of our three people who actually do. I work on what controls the division of a cell from one to two.
Brian: In one discussion we'd had about this, Paul said, "I'm the intelligent layperson." I said, "Yeah, you got the Nobel Prize." Anyway.
Linda Partridge: Yeah, hello, everyone. I'm Linda Partridge. I'm from the Institute of Healthy Ageing at University College London. And unlike Lynne, I'm not going to tell you how long I've been working in ageing research. And I'm interested in interventions, so diet, drugs, and other things that can compress that period of ill health at the end of life that Brian was talking about, that can keep us healthier for longer before we drop off the perch.
Brian: Is that a technical term?
Andrew Steele: And I'm Andrew Steele. I wrote a book called "Ageless: The New Science of Getting Older Without Getting Old." I actually was a scientist here at the Francis Crick Institute, but during that time, I discovered that even a lot of scientists don't know that much about the ageing process. So I decided I need to go and write a book and tell as many people as possible about this incredible science in the hope that we can do some more to, as Linda says, keep people healthier for longer.
Brian: And this is our panel.
Brian: Now, before we start, we've already raised that question actually about the desirability of living for a very long time. So if I am, if we do a show of hands, so if I chose a number out of thin air, let's say 200 years, so who would like to live for 200 years? Raise your hands if you would. It's interesting actually.
Linda: Quite a lot.
Brian: For those listening, it's probably less than half the audience.
Andrew: Can I add a supplement to the question? Who would say they'd like to live to 200 if they were guaranteed good health for that whole time?
Andrew: Aha.
Brian: Yeah. There's a lot more people with their hands up now. So that's interesting. So the thing is, I suppose we're imagining that we're living to 200 with the health outcomes of what we have now.
Andrew: Of current 200-year-olds, which are not great.
Brian: Yeah, yeah.
Linda: Negative.
Brian: Well, I thought we'd start with just a top-line overview to everyone on the panel. So the question would be, can we imagine living for a very long time? And let me define that, as I said, maybe a couple of hundred years.
Lynne: Right, I'm a little sceptical about that because our understanding of biology at the moment is no. As humans, there are organisms, and Andrew will talk about this, that you've got sharks living in the North Sea that are 400 years old. So biologically we know that you can live to an awful old age.
I said awful old age, it might be a good old age. I haven't asked a shark recently. But I don't think, from what we know about human biology at the moment and what we can do with human biology at the moment, we could live that long.
Brian: What would be the difference between a shark and a human being, though, in principle, so the metabolic level in that?
Lynne: Well-
Andrew: Well, yeah, I think, I think the simplest way to try and answer this might be rather than in terms of metabolism, in terms of statistics. So if you think about being a human being, every one of us in this audience, we might not all necessarily have that much in common. We've all got different, you know, skin colours and backgrounds and all kinds of things. But the one thing I know about every single person in this room is that your risk of death doubles every eight years. That means every year or so, you're gaining about a 10% increase in your risk of death.
So I said I'm 39, that means my risk of death this year is about one in a thousand. And I quite like those odds 'cause if that were to continue for the rest of my life, I'd live into my one thousand and thirties on average. But unfortunately, if you carry on doubling and doubling and doubling that, eventually it's an exponential function that gets very big very quickly. And what that means is that if I'm lucky enough to live into my nineties but unlucky enough that we haven't had any medical breakthroughs in that intervening time, my risk of death every year will be about one in six. And that's life and death at the roll of a dice.
And so you can look at this as a human and think, "I'm terrified. There's this exponential wall of mortality coming to get me." Or you can look at it as I did as a scientist and say, "You know, what is it? What's going on inside our bodies?" This fundamental ticking clock that means the increasing risk of cancer, of dementia, of heart disease, of all of these things going up with shocking synchronisation. And if we could uncover what that metabolomic, what that cellular or that biological ticking clock is, maybe we could do something about it.
And to talk briefly about those animals for a minute. This idea of a risk of death that changes so substantially with age is not universal in the animal kingdom. So there are some animals like tortoises, like salamanders, like certain kinds of fish, and they have a risk of death that's flat. It doesn't depend upon how long ago they were born. And that means that 150-year-old tortoise is basically as sprightly as it was aged 50. They seem to age without getting old. And so maybe we won't be able to live an incredibly long time. We don't have enough biology today, but we could perhaps be a little bit more tortoise.
Linda: And to bring it back to humans. And, you know, what's happening now and in the recent past, clearly our lifespan is incredibly malleable. I mean, there's been a massive increase in life expectancy since the 19th century, two and a half years per decade. But the interesting and slightly sad thing is just at the moment it seems to be slowing down pretty much worldwide.
It went at a very steady rate for a very long time. And then just before the pandemic in Europe, for instance, it's really slowed down, and in the UK, it's somewhat, you know, ticked down, our life expectancy. So in terms of reality on the ground now, I think we need new discoveries before we're thinking about these extraordinary long lives.
Brian: I think there's a lot of questions there that we're gonna cover through the scope of this discussion. So just, Paul, as the intelligent layperson. This question of is it possible for a human to live to ages 200, let's say.
Paul: Yes. I suspect not. If you look at the statistics, if you look, I mean, we've got experts here, I think we'd be doing pretty well if we had a healthy age of around 100, maybe a bit more than that, I don't know, but I can't see it going beyond.
Brian: So that raises an intriguing question. To what extent will science reveal how long any of us or each of us might live? Time for our first question.
Yodaly Sierra de Nazelle: Hello. I'm Yodaly Sierra de Nazelle, and my question is this. As a Hispanic living in London, I recently did a DNA test, and it came out that I'm like from 10 hundred different genetic backgrounds. Are there DNA or other tests that can tell me how long am I going to live?
Lynne: I mean, I'm happy to take that one. There's a lovely test called GrimAge, which predicts your time of death within four years. It's quite accurate. It's not the DNA itself, it's little chemical flags sitting on the DNA. And those flags happen as a consequence of all sorts of life experiences. They can change according to what you eat, whether you're exposed to pollution, all sorts of different things. And they tell genes whether they're switched on and off. So that's called the epigenetic clock, and that's Steve Horvath's GrimAge clock. So we have certain ways of measuring when you're going to die, which is sort of a layer above the DNA. We've got, I mean, ought to pass this to Linda because different parts of you age at different times, as you've just shown in your nature paper.
Linda: There's some wonderful work that we've built on recently, which is going a bit beyond the DNA. So it expresses RNA, which encodes the proteins, which do so much of the work in the body. And you can measure the proteins that are present in the plasma of people. You can get a sample and simply survey which proteins are there and what state they're in.
Andrew: So that's the blood for anyone who hasn't heard of plasma.
Linda: Yeah, blood, the circulation. And the fantastic finding recently is that you can analyse those proteins, you can figure out which tissue in the body, the kidney, the lung, the heart, where did they come from, and they produce a signature of how fast different organs in your body are ageing, not just the whole body. So to the extent that you deviate from the protein pattern expected for your age, if it's accelerated, then that organ's at risk, and you can show that people with that signature are more likely to go on and get the diseases of that organ. So people with fast-ageing lungs are more likely to end up with respiratory problems, and so on. And if there are problems in kidneys, it actually knocks on to multiple organs in the body.
Brian: Our next question, Caroline Stanton has sent her question in, and she wants to dig into the whys of ageing research.
Caroline Stanton: Good afternoon, my name is Caroline Stanton, and this is my question. What is the research into ageing aiming to achieve? Surely we need to halt the progressive degenerative conditions and improve people's quality of life before we extend life? Thank you.
Andrew: What a question.
Linda: Couldn't agree more.
Andrew: Exactly. Couldn't have phrased it better myself.
Linda: I think you'll find universal agreement with that on this panel. What we're about is trying to keep people healthier for longer. If it's a side effect of that they live longer, well and good, although an ethical discussion could be had around that. But the important thing, and the thing that people really care about for themselves, is their health.
Brian: How much of that, so that aim, depends on us understanding the mechanisms of ageing?
Lynne: You can treat heart disease with heart disease drugs, you can treat cancer with anti-cancer agents, but you're treating a disease that's already there, and you're treating, in essence, almost the symptoms of the disease. If we could actually get in there before these diseases manifested, then you will improve people's quality of life. And these basic biological processes are called hallmarks of ageing. And Linda was on the key paper that changed the field.
Linda: Yeah, so I think the real breakthrough discovery in recent years has been of these hallmarks of ageing. So the fundamental things that happen at the molecular level, what goes wrong with gene expression, what goes wrong in cells? How do they lose control of their protein domain? How do they become senescent? I'll come back to that in a minute. So stem cells do very strange things during ageing. They sometimes differentiate into cells when they shouldn't or fail to renew the tissue when they should. Different tissues talk to each other. There's a lot going on in the systemic environment. So it's a complicated process, but we really understand what its essentials are. And many of them can be targeted genetically with mutants or with drugs. And what we find is that we can often go for one mechanism of ageing, but then the organism is protected against multiple things in different tissues that go wrong later. This is the geroscience idea. Target one thing often with a single drug, and you can have a preventative effect on lots of the things that happen later. And I think that's the approach that we would all like to see come into medicine. Preventative, but also the idea that you can prevent multiple things simultaneously.
Brian: Paul, I think it's a good example, isn't it, of the, so the Crick Institute, a multidisciplinary institute studying biological sciences like life. But as we've seen with what we've been discussing, that it's so complex, research into one area can have a profound influence on research in another area. So if that's the case, when we talk about ageing, we're talking about all of biology essentially.
Paul: Yes, so we don't have a sort of ageing initiative, but what we do have is 120 research groups here with no discipline boundaries. And that is extremely unusual. So what this means is we mix up different scientists from different disciplines and don't have departments that tend to fight with each other for resources and power and money. We have a structure, but it is not discipline-based, and that is very unusual.
Now for a topic like ageing, as we've just been hearing, which is clearly multidisciplinary. That sort of approach is, I think, important. And I wondered if I could extend and ask a question of my experts. I think what you're saying is that we have, and I'm perhaps oversimplifying this, we have a series of different sort of systems, let's call them organ systems, and that there are common reasons for death which involve, I dunno, four, five, six, seven of these, which are probably ageing each one of them. And what Linda has just said and what you've just said is that we can now test which ones and where they've gone. So is it now possible for us to sort of think about it in terms of these different organ systems and targeting each of those in some sort of separate way that we could actually try and combine together. But at least taking an individual, what is the most vulnerable one?
Linda: I think that's going to be the big wave in the next few years is understanding. If we know we're looking at someone who's got problems with their lungs, so ageing too fast. Even though they're completely subclinical at the moment, what preventative interventions can we do to protect them from that vulnerability so that their lungs manage to keep up with the rest of them?
Lynne: Can I chip in there with an example, very specific example? Linda's mentioned cell ageing, it's also known as cell senescence. And if you think of cancer, normal cells in the body go weird, they behave badly, and they cause a disease. As we get older, our cells accumulate damage, damage to their DNA, damage to other parts of them. And if they're essential to you being you, they don't die. They hang around, but they're different, so we call them sometimes zombie cells. And our zombie cells change in really weird ways. So mine are currently kicking out enzymes that are degrading the collagen, the structures that support my skin. So if you ever look in the mirror and see there are crow's feet coming on, that is your senescent cells accumulating and eating away the tissue structures in you. So senescent cells can be quite harmful, and we know that they're harmful in multiple different parts of the body. If you inject senescent cells just into the abdomen of a mouse, it gets old across the whole body. If your immune system is old, you get old across all your different organs. So there's some really cool research now showing that if you actually get rid of senescent cells in a middle-aged or even an old mouse, that mouse shows improvement across multiple domains. So better cognitive function, its brain works better, it's stronger, it has more energy, its fur is better, its behaviour, it's less anxious, and if it gets cancer, it has a much better rate of cancer survival. So removing senescent cells from old mice looks really promising. And that's now in clinical trials in people. So for diseases where we know senescent cells are a key driver, like idiopathic pulmonary fibrosis, where your lungs just fill up with senescent cells. So there are some really exciting developments in the field where we know some of the mechanisms. There are drugs that can do something about it, and they're being tested. So I would say optimistically, we have therapeutics that can get in there that have an early preventative effect across the board.
Andrew: And I would definitely recommend if you go home and search the internet for pictures of the mice, sort of before and after photos with these senolytic drugs. I was a computational biologist back when I worked at the Crick, so I didn't deal with mice at all in my day job. You do not need to be an expert to see the difference. The mice just look younger, they look fantastic. They should be on the cover of "Vogue." So, you know, obviously that's a really visually striking thing. But what we know is these hallmarks of ageing, not only do they cause the crow's feet around your eyes, not only do they make your hair go grey, they're actually causing those same kinds of processes in your arteries, in your blood vessels. They're causing the risk of cancer to increase, and those things are much harder to see, of course. But since they're driven by those same hallmarks, if things look good on the outside, they often look better on the inside too. And that shows that we're keeping those mice healthy in really almost every way for longer.
Brian: You mentioned removing the senescent cells. What do we know about why they become senescent or behave like that in the first place?
Lynne: Well, it's an evolutionary mechanism. So most things that happen in biology have either been selected for or against over evolutionary time, and we need senescent cells. So when you're young, you fall off your bike, you cut your knee, you have a wound, and that wound has to signal to the rest of the body, "Look, come and heal me." So it's sending out signals to the immune system to come along and remodel the tissue around the wound and fix the wound. So we know that senescent cells are part of that. All these nasty chemicals that they're kicking out when we get older are actually beneficial chemicals when you're young. So senescent cells are good for wound healing. They're also a way of stopping cells from becoming cancerous, which is an incredibly important thing to do. And of course those things are before the evolutionary cutoff. Once you stopped having babies, then you're in the evolutionary shadow, and so the selective pressures against accumulation of senescent cells may not happen. So these things just build up over time. And because your immune system gets a bit bleurgh with age, sorry, that's a technical term. Your immune system is less good at coming and finding the senescent cells and weeding them out. You just accumulate with age, so you get more and more and more of them, and then they do harm as they accumulate.
Linda: And just coming back to the interventions you were asking about, you know, the anti-senolytic cells and so on. There are lots of drugs that already target the network I've just talked about 'cause it's very important in metabolic disease and in cancer. So there are drugs there already. And it turns out that if you use these drugs at low doses in animal models, mice for instance, you can actually produce a very broad spectrum improvement in their health during ageing. The kind of geroscience that I was talking about earlier. But we're facing a real problem in the field. There are lots of these drugs out there. We know, or we strongly suspect, that if we repurpose them to be used at lower doses, they would have a great preventative effect on health or loss of health in old age in people. But these are drugs that have been off patent for years, and you would have to have a completely fresh set of clinical trials if you were going to use them preventatively for the diseases of old age rather than to treat a disease at the time. So there's a problem there. We really need a lot more public funding coming in to looking at these drugs and repurposing them.
Paul: I think that's really important, the point you just said there. We always think in this context of commercial development of drugs. Commercial development of drugs is driven by profit. The health of society and the nation is driven by different things. And we have to start thinking more about public-private partnerships, where the public engagement in these activities is looking at the what is good for society rather than good for the profits of the company.
Linda: Absolutely. I mean, the behaviour of the pharmacists is completely understandable. You know, that's their business model.
Paul: That's their business model, yeah.
Linda: But then they're not going to touch these drugs 'cause there's absolutely nothing in it for them.
Paul: And the business model of the public is completely different.
Linda: Yes. And likely, I mean, there are huge inequalities in health during ageing. And these drugs, I think, are likely to be particularly beneficial to people who are not ageing healthily.
Andrew: I think this is something that we could really do well in the UK because of the NHS, because we have this National Health System. And in fact the same with the clinical trials we were just talking about. There was a fantastic clinical trial in the UK called RECOVERY, which happened during the pandemic, where everyone who went into intensive care for COVID was randomised. They were given a different drug at random because we didn't know what was going to work. And we could do this with these so-called geroprotectives, these sort of real anti-aging drugs. It could be that every time you go into a GP, if you're over the age of 60 or 65, a little light flashes up on their computer and they say, "Would you like to be involved in this trial?" And they might randomise you to one of these drugs that we think has an anti-aging effect. And we can see if people do stay healthier for longer as a result. And this is something, there's a drug called metformin, which is often spoken about. It's a diabetes drug. There are probably a lot of you in the audience taking this 'cause it's the first-line therapy for diabetes, and there are some indications it might slow down the ageing process.
The problem is, just as Linda said, it's out of patent. I think the NHS can get it for a few pence per pill. So no one's gonna make a huge amount of money if this trial turns out to be successful. But that means the NHS is in a fantastic position to hand out this incredibly cheap medication to a large number of people and potentially save the health system a huge amount of money.
Brian: Okay, I like this next question. It is a bit left field, but let's see what our panel thinks.
Akima Fashanu: Hello, I'm Akima Fashanu, and my question is, could the age regression ability of the immortal jellyfish be adapted for humans to achieve a similar effect? Thank you.
Lynne: Good question.
Brian: The immortal. Someone describe the immortal jellyfish.
Andrew: The immortal jellyfish. Well, this jellyfish is-
Brian: Immortal.
Andrew: It's not technically immortal. It can still get eaten, it can still get a disease, but it's what we call biologically immortal. And that is, it's this property that I talked about earlier, where you have a risk of death that doesn't change depending on how old you are. But the way this jellyfish does it is really unusual. It starts out as what's called a polyp. That's how all jellyfish start their lives. And then it grows up into an adult jellyfish. That's the thing with the stingers on that, you know, undoubtedly you've dodged at the beach at some point. And if it finds itself in a stressful situation, it can turn back the biological clock. It can revert to that early polyp stage.
Now we wouldn't want to do this directly for humans because what that would mean is you'd turn all of your cells back into being stem cells, and then you'd redifferentiate, with any luck, back into an adult. And that would mean your brain would turn into a stem cell-based mush. And everything that was important about your personality would disappear during this process. So that's not a great idea. But we can do this in the lab if we're a little bit more subtle about how we do it. So back in 2007 or 2006, I think actually, a guy called Shinya Yamanaka and his team identified a series of genes, which are now called the Yamanaka factors, that can turn back the clock inside cells. And if we put these genes into mice, if we leave them turned on permanently, it's very bad news for the mice. They get a lot of these stem cells. Stem cells are very powerful in terms of being able to become any cell in the body, but they're very, very bad at being a liver cell and detoxifying your blood or being a heart cell and beating. And so what that means is if these genes are constantly active, the mice die of organ failure, very sadly.
But they found that if they give these genes in special form where they can be activated with a drug and then they turned on these genes effectively at weekends, they turned them on two days a week and then five days off, they found that they could rejuvenate the cells in the mice and keep them healthier, but without having them turning all back into stem cells and losing their cell identity. And actually this is one of the hottest areas of ageing biology at the moment. Some of you might have heard of Altos Labs, which is a $3 billion, quote, unquote, "startup." I'm not sure with that kind of endowment you can call it a startup, but it's backed by a number of people, including Jeff Bezos, obviously the guy who founded Amazon. And hopefully $3 billion is enough to have a serious go at turning this from something which works, you know, in mice in the lab to something that maybe we could use to treat diseases in people.
Paul: Could I ask a question of the panel based on the jellyfish? What are the good models for looking at ageing and why?
Andrew: Well, I think currently, we're very limited in the way that we use models in science. Like, it's exactly the same as the models that, you know, colleagues in any part of biology would use. It's yeast, it's worms, it's flies, it's mice. But the problem with a lot of these species is they're very short-lived. But there's another animal about the same size as a mouse called a naked mole rat. Looks a bit like a penis with teeth. They're not the most beautiful creatures.
But these animals, they're the same size as a mouse, but they can live up to 30 years old, and they seem to be essentially immune to a lot of age-related diseases. They have very low rates of cancer, very low rates of neurodegeneration. And so maybe as a field, we should be turning our attention to some of these incredibly long-lived species that live a really long time for their age, finding out what naked mole rats have that mice don't, and whether we can bottle that and give it to human beings.
Lynne: And the bowhead whale. So there's some people doing comparative evolutionary biology, looking at animals that live a long time and looking at their genes and which genes they have either more copies of or switched on more highly. And there's one particular gene called SIRT6, which is a DNA repair gene that is at high levels in animals that live an awful long time. And then you take it back to humans, and you look at centenarians, and we've all got this gene called SIRT6, but centenarians have five different letters in the alphabet of that gene. And if you make a copy of the gene with those five differences, the centenarian version, it's much, much better at repairing DNA than the genes that most of us have got. So we can learn from super long-lived animals, we can learn from super long-lived people, and we can actually make a difference. We can understand the biology by starting to turn these clocks back.
Brian: The next question turns to lifestyle choices in shaping human ageing.
Anjna Kotecha-Karia: Hello, my name is Anjna Kotecha-Karia, and my question is, what is special about people who live long lives? Is there a link between diet and long life? And is it true that there is evidence that fasting can extend your life? Thank you.
Lynne: Yeah. Well, can I kickstart that with some studies on centenarians in Japan? We're not just human, and people tend to forget that, that we are made of human cells, but we're also colonised by billions of bacteria, and viruses, and fungi that live in us and on us. And the Japanese team were looking at the microbiome in the gut, so all the bacteria that live in the gut. And they showed that supercentenarians, people over 110, 115, had a different composition of bacteria in their gut. So they had all the normal bugs that we've got, but some other ones as well. And then they narrowed it down to a couple of species of bacteria that were making a chemical, it's called a bile acid, but it makes a chemical in the gut that kills off harmful bacteria. So you can take that chemical, and you can put it on nasty disease-causing bacteria, like C. difficile. It kills them. So these people are actually making their own antibiotics in their gut, which is a phenomenal finding. And that microbiome is Japanese-specific. And of course people in Japan tend to have an incredibly healthy diet. I felt like I was on detox when I went over there. I felt just so much more alive. Natto, fermented soybean, has components in something called spermidine, which is actually, we know triggers a process of waste removal within the body, autophagy. So what they're eating is very good for them, and it also supports a very healthy microbiome.
Linda: I think we can also learn a lot from just, you know, straightforward inequalities in life expectancy in different social contexts. So within the UK, if you just look even over quite short distances between different parts of cities, you can get a 10-year difference in life expectancy. And it's really tied up with socioeconomic factors. So if I was going to advise people on the one thing that's really important to be healthy during ageing, it would be exercise. But you need to have the kind of lifestyle where you can factor in the time and the opportunity to get exercise. Healthy diet also very important. But again, eating healthily is actually more expensive than eating unhealthily. So I think we need to tackle these basic socioeconomic things almost first. I mean supercentenarians are very interesting, but there's something much more important straight in front of us that we need to deal with.
Lynne: But the diet and the fasting was raised as well.
Brian: Yes.
Lynne: And, we know-
Brian: Because that comes up a lot, doesn't it?
Lynne: Yeah.
Brian: The intermittent fasting or lowering your calorie intake and these ideas.
Lynne: I mean, from the 1930s, we knew that if you gave rats 30% less food than they would normally choose to eat, then they lived a lot longer. And so caloric restriction has been shown to be true in all species that's being looked at.
Paul: Were they happy? Were they happy rats?
Lynne: Well, as Linda will tell you, you can have dietary restriction without malnutrition.
Andrew: There is a running joke in ageing biology that maybe fasting won't make you live longer, but it'll certainly feel like longer.
Lynne: It'd feel like it.
Linda: Yeah.
Lynne: So we know that caloric restriction can work, and we know that intermittent fasting can work. I have one caveat with that, that a lot of people are saying, "Oh, just fast." The studies in mice have shown that if you are young and middle-aged, fasting can actually increase your life expectancy. If you're old, it can increase your risk of mortality. Old people are very vulnerable to any changes, and it can just push them over that edge of not being able to cope metabolically. So Linda's done a lot of work on dietary restriction.
Linda: Which Lynne has described the whole thing brilliantly. But the other thing about older people is that they probably need a higher protein diet. It's not just the amount they eat, but what they eat. So sarcopenia, you know, muscle wasting, is a real problem in older people, and to some extent it can be combated by increasing the amount of protein in the diet. So there are composition issues as well as. And also when you eat is very important. There've been some very nice studies in mice, now that they've developed automatic feeders, showing that they're much healthier if they're doing the eating that they do during the wake period. If you feed them during their night period, they develop really bad metabolic problems. They haven't looked at lifespan, but it's clear from the metabolic changes that it would probably be shortened. And that may be one of the reasons that shift work in humans is associated with ill health. It's partly eating during what should be the rest period, the night period.
Brian: Right, so if we imagine that we do all live longer lives, our next questioner wants to know about the societal implications of that.
Richard Goody: Hello, I'm Richard Goody, and my question is, what are the societal impacts that the panel envisage we would need to tackle arising from an increasing population of super elderly? Thank you.
Brian: Who would like to take that?
Lynne: I could start. You look at Japan, and 30% of the population already are over the age of 65, and they're having major problems with the dependency ratios. So the number of people in work who are earning money to pay for and look after the people who are over 65, generally in poor health who need looking after. So they're developing robotics to change people's adult nappies. They are doing all sorts of things. There aren't enough young people to look after the older people. And this is a major, major problem in intergenerational fairness. I struggle with looking at societies where all of us are getting older, and we're expecting fewer and fewer young people to just keep working for longer to keep us in our pensions and our healthcare. So the only way to tackle that really is to keep people healthy and economically active until a lot longer. We gonna restructure society because it's not tenable the way we are doing it at the moment.
Brian: It is interesting, isn't it? Because I think many of us think, when we say we'd like to live longer, healthier lives, you think longer retirement. But what you're essentially saying there is that does not follow.
Lynne: But retirement isn't necessarily good for you because there are a lot of studies suggesting that as soon as people hit retirement, their health deteriorates. And the sense of purpose is one of the things that keeps people healthy. The psychoneuroimmunology. There's a lot of being positive and optimistic in knowing that you're doing something useful that keeps you going.
Linda: The original idea behind retirements, I think it was Bismarck who first introduced them, was that they were really a safety net for people who'd had industrial injuries or, you know, were in bad shape after a lifetime of manual work. And the vast majority of people never lived long enough to collect a pension. So this idea of a long retirement is very much a modern thing. I think the other point is that the dependency ratio also depends very much on fertility rates. So things are really bad in the Far East at the moment because fertility is also so low. Actually, if the whole thing equilibrates so the population is at replacement, but with everybody living longer than they do at the moment, the problem would be a lot less acute.
Paul: So it's a complicated issue actually because I mean the natural consequence of this is that we retire at older ages, but then we have to consider what we're capable of doing at the older ages. And, you know, we're sitting here with sort of white-collar jobs. And it really could be quite different if you're digging in the road. To have a certain age sounds very sensible and fair, but actually it probably isn't.
Linda: It's actually very unequal.
Brian: We do have a question actually from the audience that feeds into what you said about extending that, your healthy lifespan.
Andrea Juste: Hi, my name is Andrea Juste, and my question is, what are three to five things humans can do to help increase our health span?
Brian: Yeah, three to five.
Lynne: Well, we've touched on a few of them. So decent diet, so particularly plant-based diets, are looking extremely important because they support a healthy microbiome. Exercise, as Linda has pointed out. There's some really beautiful data about what exercise does to us. So there's a study in London and Birmingham looking at super cyclists. So people who are on their bikes, cycling over a hundred miles a week. And their levels of inflammation, nasty chemicals floating around in your blood, are way lower. So these are people in their 70s or 80s, their inflammatory levels are down what you would expect for a normal 40-year-old. So the exercise is damping down all the nasties, keeping you healthy. So exercise is helping you metabolically, it's preventing inflammation, which can drive all sorts of damage to your tissues and organs.
So diet, exercise, sleep. And that's something that we're really bad at in the West. We don't get enough, it's not just enough sleep, it's the right sleep. And as Linda has pointed out, the social inequalities. Don't live somewhere that's got loads of pollution. Don't live somewhere where you are so stressed to walk on the streets. Don't live in somewhere where you experience racism. There's one really shocking study from King's College London that Black women who experience racism during pregnancy give birth to children with short telomeres. Now your telomeres tell your cells how old they are. So these babies who are born to mothers who experience racism are actually older than they should be. Now that's incredibly shocking that those psychosocial things impact our rate of ageing.
So one final thing on that, optimism. Andrew is optimistic. Beautiful study of nuns entering a convent. They live the same lives, they have the same amount of exercise, same diet, same amount of sleep, all those things are controlled, but what's not controlled is their personality before they went in. And the ones who wrote letters home who were optimistic lived on average 10 years longer than the ones who were pessimistic, so those would be my points.
Andrew: Can I give what I think is the single most important piece of unconventional health advice? 'Cause I suspect a lot of people know they should diet, exercise, and sleep. And if you're already trying to do most of the right things and fortunate enough to live in a nice neighbourhood, the single most important thing you can do, not just for your health but for the health of everyone around the world, is to campaign for more funding for ageing biology research.
Because, and bear in mind, I'm not a scientist, I'm not getting these grants. Because what that means is we can develop some of these treatments that will help people, even if they are living in poor neighbourhoods, even if they don't have time for exercise, to stay healthy for longer. So I think getting people's attention, spreading the word about this science, getting politicians to know that, you know, if they invest in ageing biology, you will vote for them, could be the single best thing you can do for your health.
Brian: So we have a question actually, which was from the audience, from Sally Horton, which feeds into what we've been talking about which is, "Which has more impact on ageing, genetics or environment? Or is it a complex interaction between the two?"
Linda: I think the answer to that is pretty clear actually. It's much more environment-
Andrew: It's interesting.
Linda: than genetics.
Andrew: Because it varies by age, doesn't it?
Lynne: Yes.
Linda: Yes, it does.
Lynne: Once you're 100, then genetics becomes more important.
Andrew: Exactly.
Lynne: But up till that point.
Linda: But for the vast majority of ill health and death, you're looking at environmental factors, lifestyle factors, what you're exposed to.
Brian: It goes back to what you mentioned earlier, Linda, about the fact that it may be, it's socioeconomic interventions that may have as big an effect as generating new knowledge on the biology.
Linda: Well, it's a big public health issue, yes.
Andrew: Can I make the case for biology in the Francis Crick Institute of biology? I think the reason that I'm really so excited about the medicine is because public health is really, really hard. And I don't think we should give up on public health. I think it's super important. But I've got a three-month-old baby at home. I know I need to exercise, I just don't have any time. And I know that a lot of people are in the same position.
And if I had some drug, I'm not saying to replace exercise, but to help me keep my health good at a time when I'm finding it really, really hard, I think that would be hugely beneficial. And I think there are so many people around society in that position. They're, you know, trying to earn a living, trying to make their rent, trying to cook food for their three kids. You know, people need help with some of this public health stuff, and we should be doing that at the same time. But I think if we could develop some of these medicines, it'll be a really good adjunct to support those public health measures at the same time.
Lynne: Can I say we need different interventions across a life course. We need the biomedical interventions right now for the people's suffering age-related diseases. We need those preventative interventions for the people in their 40s and 50s at high risk of getting them. But we also need the socioeconomic stuff that's going to prevent any of those risk factors occurring. So I think we need a completely holistic approach across society. And public health, definitely early on. And we've shown the doubling in life expectancy over the past a hundred years has been soap and sanitation. That's public, and vaccination, public health interventions that really, really work. But those were the low-hanging fruit, and now we've got to be a bit more creative about those interventions.
Andrew: Yeah.
Brian: So I think just, if I was to ask you to summarise, I mean, it seems to me that the ageing, we've chosen something that cuts across everything. It's about fundamental biology, it's about health, it's about economics, it's about society as a whole. So it's probably the most complex subject we could have chosen. Well, thank you very much. That is all we've got time for today. So, thank you all to our wonderful panel. Professor Lynne Cox, Professor Sir Paul Nurse, Professor Dame Linda Partridge, and Dr. Andrew Steele.
