Instant Genius - Simple ways to slow your biological age (and maybe even reverse it)

Episode Date: December 29, 2023

How would you like to slow, stop or even reverse your body’s ageing? Although that might sound like science fiction, a growing body of research suggests that ageing isn’t inevitable, that you can control a large proportion of how you age. How exactly? That’s just what we’ll be unpacking across two episodes with guest Andrew Steele, the author of Ageless: The new science of getting older without getting old. In this first part of our anti-ageing special, we’ll go through how to assess your own biological age, and how to slow it with several simple lifestyle changes. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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so you can experience exceptional sound at home. Music just as the artist intended. Visit name audio.com to learn more. Oh, and welcome to Instant Genius, the Bitesize Masterclass in podcast form. I'm Thomas Ling, digital editor at BBC Science Focus magazine. How would you like to slow, stop, or even reverse your body's aging? Although that might sound like complete science fiction, a growing body of research suggests that aging isn't inevitable,

and you can control a large proportion of how you are. age. How exactly? That's just what we'll be unpacking across two episodes with guests Andrew Steele, the author of Ageless The New Science of Getting Older Without Getting Old. In the first part of our anti-aging special, we'll go through how to assess your own biological age and how to slow it with several simple science-backed lifestyle changes. Hello, Andrew. Welcome to the show. Hi, thanks for having me. Fantastic. So I, um, I think you've got quite an interesting story about your route into the science of aging. You didn't start off as a biologist, did you? No, I didn't exactly take a straight line path, as you could say,

into their biology. I actually got as far as finishing a PhD in physics before I decided that aging was the most important scientific challenge facing us. And the reason I changed career actually is because of a graph. So it's quite a simple graph, I guess being a physicist, being a numbers nerd is the reason that something like that was able to change my career. The graph is how old you are versus your risk of death with time. And it's a surprisingly simple graph, actually, in that respect. And I think all of us know that older people are more likely to die. But just how much really shocked me. So I'm 38 at the moment, which means my risk of death is about 1 in 1,000 per year. And actually, I quite like those odds. Because if you think about that,

if that was to stretch out into the indefinite future, I'd live into my thousand and 30s on average. But unfortunately, of course, that isn't what happens. And humans have something called a mortality rate doubling time. So let's unpack that. Mortality rate is your risk of death. Doubling time is how long it takes for that risk of death to double. And for a human being, that's about eight years. And so what that means is we can take that one in a thousand that I feel fortunate to have right now. And if we carry on doubling and doubling and doubling it, if I'm lucky enough to live into my 90s, but unlucky enough that there aren't any breakthroughs in medicine, in aging biology, as we're going to be talking about in the intervening time,

I'll have odds of death every year of about one in six. And that's life and death, the role of a dice. And so there are a couple of ways you can look at this, right? You can I think, well, this is terrifying. I'm a human. I've got this exponential wall of mortality coming at me. Or you can look at it as a physicist and think, what is it that causes this remarkable, synchronized increase in the risk of death? And it's really an incredibly universal property of being human, by the way. So anybody listening to this, your mortality rate doubling time, I'm sorry to inform you, it's about eight years. If I were to pluck someone from the Amazon rainforest, some undiscovered tribe, their mortality rate doubling time would be eight years.

We could go back, you know, 500 years in history, 10,000 years in human history. and find someone from one of those places and times, we would find that their absolute risk of death might differ quite a lot. Obviously, life expectancy has changed, but their risk of death doubling time would be about eight years. It's a universal fact of being a human being. And so the real question scientifically is,

can we understand what drives this synchronized, sort of ticking clock inside all of our biology and do something about it? There seems to be a lot of buzz recently about the science of anti-aging. There's a lot of interesting research that's been done, and I think we should probably start by asking the basics about these studies. And that comes back to a concept called biological age.

Can you outline what biological age is? Yeah, and it sounds like it could be quite a technical concept. But actually, I think it's quite an intuitive one to most of us. Because we've all got friends or relatives, you know, someone who's age 60, who might be bounding into their 60s, you know, they look like someone 10 or 20 years younger. And at the same time, we might have another friend or relative who unfortunately, you know, just looks haggard, they've got, you know, deep wrinkles in their skin. they might be suffering from a few age-related diseases.

And we can just see that these people, although they've got the same number of candles on their birthday cake, they've actually aged in very, very different ways. And scientists in the last sort of 10 years have really started putting some meat on this intuition. So this actually, I think one of the most sort of interesting and, again, intuitive studies was done in 2009. They got a panel of both regular people off the street and some expert nurses who are really used to dealing with older patients

to rate the perceived age of a series of photographs of patients. and what they found was that those patients who were rated as looking older actually got ill sooner, they died sooner than the patients who are perceived as looking younger than their chronological age. So clearly even external appearance reflects something fundamental about your aging trajectory. And we've since managed to come up with some slightly more sort of scientific sounding approaches. For example, we can measure your biological age with something called an epigenetic clock, which people might have heard of. And this is a test where you can do a blood test.

You can actually take a sample from anywhere in the body, but blood's normally the most convenient. and you can look at the DNA inside the cells. And all over that DNA are what are called epigenetic marks. And in particular, the one that most people are focused on is a mark called methylation. And if you look for the places in the DNA where this methylation has happened, you can see that there's a change in the locations over time. There's a change with age. And so when they first did these experiments,

they calibrated against someone's normal age, someone's chronological age. Again, how many candles there are on their birthday cake. What they found was there was a bit of an error, sort of an uncertainty in the measurement. I can tell you how old you are, but plus or minus four years. So you might be thinking, well, that's not very scientifically useful. We have a technology that's far simple. It's called birth certificates that allows us to do that with infinite precision. So the issue is, what does this error mean?

Is this just because the test's a bit uncertain? You know, it's not quite a fully accurate test? Or does it mean that someone who's got an epigenetic age acceleration, as we call it? So someone who's older than their chronological age. Are they, in some sense, biologically older? Or conversely, you can be biologically younger. You can have an epigenetic age that's younger than the number of, number of candles on your birthday cake. So the answer seems to be yes. So we've done more

sort of detailed studies on that in the last 10 years. And people who are biologically older, again, tend to get diseases sooner, tend to get unwell, tend to die more rapidly than people who are biologically younger. And what we're trying to do now is dig into what are the mechanisms that cause these changes in the epigenome, change in these methylation marks, and see if we can work out a way to reverse that and meaningfully reverse, you know, some other things we care about as part of the aging process as well. Because obviously, I don't really care where the positions of the methylation sites are in my DNA. What I care about is, am I free from cancer? Can I still lift things up and unscrew the top of a bottle and get up and

down the stairs and play with my grandkids as I get older? So I try to sort of bridge the gap between this very sciencey stuff and things that people actually care about. So this thing, you just mentioned things like sort of going up and down the stairs. Are they quite a good marker of someone's biological age? I think that's actually, yeah, really remarkable insight. One of the scientists I spoke to when I was writing my book said that all these sort of newfangled blood tests and epigenetic tests and all these different things. The measurement they really have to compete with is grip strength. So you can get this little grip strengthometer, which you grab as hard as you possibly can.

And this turns out to be a remarkable predictor of your future health, your future length of life. And so, yeah, there are all kinds of these functional tests. You can look at how quickly you can walk 10 meters. You can look at how quickly you can rise out of a chair. Some of these are only suitable when you get toward the sort of frailer later part of your life, like maybe for people over the age of 60 or 70, because basically, you know, most young people can do these relatively quickly or in a relatively similar way. But it really is remarkable. I think this comes back to this idea that the visual external signs, and you can literally look at someone's face and judge how biologically old they are. It's because now we've started to understand a bit more about the aging process. We realize that it's the same

underlying biological mechanisms, whether you're talking about risk of cancer, whether you're talking about skin wrinkles, whether you're talking about loss of memory or anything else that you might be worrying about. The same underlying biology is going on. And so you can infer from how or someone can climb the stairs or how wrinkled they look, how, you know, how age of their blood vessels are, how much risk of cancer they're at. And it's this remarkable underlying constellation of factors, which is what's really exciting about ageing biology. Because now we've identified these underlying processes. The idea is we can perhaps try and intervene in them and slow the whole thing down or maybe even reverse it. To why extent can a person slow down or reverse their

biological age? Is that still not quite clear? I think the sort of the long-term answer is, we just don't know. And fundamentally, it might be possible to just, freeze it and completely reverse it to the sort of really low age of a young adult, for example. You might be able to reduce your risk of death to one in a thousand per year, just like someone in their 30s. And the reason that we're optimistic that that's possible is that there are animals out there in the animal kingdom that already do this. So there's a property that's known as negligible senescence. Senescence is just the sort of technical, biological word for being old. Negligible just means not very much. And these are animals that don't have a mortality rate doubling

time. Their risk of death is flat. Doesn't matter how long ago they were born, they've got the same risk of dying every year. And that means in this statistical sense, and I think in a biological one too, they don't age. And you can look at them, you know, so there are animals like tortoises, for example, these are negligibly senescent certain species. And what you can see is these tortoises don't get more frail with time. They don't lose any of their function. They can even stay reproductively active until, you know, very, very late in life. So they really don't seem to age in any biological way. What's a bit annoying from an ageing biology point of years, these aren't sort of the beautiful poster children of anti-aging. They're wrinkly from a young age.

not exactly fast moving, but they are nonetheless as sprightly aged 150 as they were aged 50, for example. So that really shows us that there's nothing biologically stopping us from reversing our aging and potentially keeping our risk of death flat with time. The real question is, you know, what can we do today to try and impact upon that? And I think at the moment, it's going to be a lot of, you know, some of it's going to be following basic health advice, some of it's going to be using a few sort of tips and tricks that understanding aging biology shows us. But the future, I think, the really exciting stuff coming in the next sort of five, 10, 20 years in plenty of time,

for most people alive today, is taking that understanding of aging that we're starting to develop and turning it into medicines, into drugs, into treatments that can keep us all healthier for longer. Do we have an idea of how much somebody's genes could impact their lifespan? That's a really good question. And we don't want to be sort of genetically fatalistic about this and think that your lifespan is entirely written in your genes and there's nothing you can do about it. And actually that scientifically really doesn't seem to be the case. So it depends of it, how you do the statistics and which study you look at. But we think that somewhere between five and 20, of how long you live is determined genetically, which is really not that much. So that means that somewhere

between 80 and 95% is down to something else. And that's something else is lifestyle and it's luck. You obviously can't take luck out of the equation. But lifestyle is something that a lot of us, you know, can do something about. And this applies to people who, you know, if your parents live to their 60s or 70s or 80s, you really shouldn't see their lifespan as a ceiling on your lifespan. We know that there's a lot that you personally can do. The place where this changes a bit is if you're talking about people who make it into their 90s or especially 100 plus. These people are centenarians. They're called people who make it to over the age of 100. They do seem to have some sort of almost magical genetic resistance to age-related disease. And you find that if one of your parents or if one of your

siblings made it to above the age of 100, you have a 10 times greater chance of doing so yourself compared to the general population. So there's clearly something going on in the genomes, in the DNA essentially of people who get to these really extreme ages. But for most of us, it's all to play for. I feel it's really interesting when you mentioned luck there. What does that exactly mean in this context? Is that just accidental deaths? What it means is that actually the aging process is surprisingly the sort of technical term is stochastic. And what that really means is random. Because, for example, let's take cancer. Cancer is an age-related disease. And there are a variety of different reasons for that.

But essentially what has to happen is a cell has to accumulate a certain number of mutations, so mistakes in its DNA. And what those mistakes mean altogether is that the cell, rather than doing what it's supposed to do in the body, it carries on dividing and dividing and dividing and essentially can do so an indefinite number of times. And that can eventually go into a tumor. When that tumor gets big enough and it accumulates a few more mutations, it can spread around the body in a process called metastasis. And that's ultimately what goes on to kill us. But, you know, what causes these mutations? Well, essentially, some of this is luck. Because say there are 10 mutations required to make a certain cell turn into a cancer. You know, one of those mutations might come from

drinking alcohol or something like that because, you know, we know that these things can induce mutations in certain parts of the body. Another mutation might be caused by a random bit of radiation that just happens to strike that particular cell, and that gives it a second mutation. A lot of the mutations are actually just a side effect of being alive. So like when our bodies metabolize food, when they turn food into energy, by their very nature, these molecules, the food, the oxygen, it's burned in, essentially. They are high energy molecules, otherwise you couldn't generate energy using them. And that means occasionally your cells will fumble those molecules. And these sort of fumblings can cause mistakes in your DNA. So there are all these processes which have a huge, huge,

random component. So it could be that you can follow all the best lifestyle advice. And unfortunately, you can still get cancer early if you just happen to get unlucky. So there is just this huge, huge component of luck. And it's the same if you think about something like heart disease or a heart attack. Most of us have these sort of buildups of, they're called plaques in our arteries. But whether or not one ruptures on a particular Tuesday morning and gives you a heart attack, again, it's just very, very random. And I think we just forget, although you know, you can follow all the best lifestyle advice you possibly can. But at the end of the day, Lady Luck has a surprisingly big say in our health. So I can't hold off asking the question anymore. What are the things that people can do to at least

slow their biological age? So is there some sort of pill that people should be taking right now? I think we're not yet at the stage of people being able to take pills. And the health advice that I would give people sort of splits into a couple of different categories. The first category is, I think, the obvious stuff, you know, basics that I think most of us really know we should be doing anyway. But understanding a bit about the aging biology actually makes these sort of boring health advice sound an awful lot more exciting. So this is things like getting enough exercise, not smoking is a really, really important thing. If you want to live a long life and you smoke, that is probably the first thing you should stop eating well. It's getting a good balanced diet.

It's trying not to be overweight. And the reason these things are made much more exciting by understanding the aging biology is because we now know that those essentially accelerate the aging process. So let's take the example of exercise. When you go out an exercise, you can clear. feel, you know, you can feel your lungs, you know, as you inhale and exhale, you can feel then working, you can perhaps feel your heart beating in your chest. You understand that your muscles and your legs are being exercised and you go for a run or a bike ride or whatever. But what we've found is it doesn't just benefit these narrow systems within the body. It seems to have this systemic effect, whereby it slows down aging in a whole variety of ways. So we know, obviously, it can

decrease your risk of heart disease. But exercise can also decrease the risk of certain kinds of cancer. It can even decrease the risk of dementia. And there are a variety of different mechanisms through which it does this. But I think that just makes it a lot more exciting. I'm trying to persuade myself to go out for a run on a cold, cold, rainy morning as we quite often get in Berlin at this time of year. You know, thinking that's not just improving my heart health, but actually slowing down the whole of the aging process is really exciting to me. I think another thing that's often overlooked when it comes to exercise is strength training. And the reason that that's so, so important, particularly as you're getting into sort of middle age and older age, is that we start to lose muscle mass

every decade after the age of 30. And what you find is that people who have more muscle mass in older age, often have much better health outcomes. And I think it sounds obvious as an example, but it's surprisingly important, is that if you've got good muscles, if you've got good balance, you're less likely to fall and break a bone. And the reason is that another thing that aging does, as well as predisposing us to particular diseases, it can make things that we would have shrugged off as a younger person be really, really serious problem. So if I'm unlucky and I break my leg or something like that, I'm going to go in a cast, I'm going to spend a few weeks, maybe a month or two in a cast if I'm unlucky, and then my bone will essentially heal. But if an older person

loses their balance, you know, loses their step on some, some slippy eyes. You can see I'm really channeling the Berlin winter energy here. Then what they can do is they can fall, they can break their hip. And that can be a hugely, hugely, hugely serious thing for an older person. It can often be the beginning of the end essentially. If you look at sort of the six or 12 month mortality, so the risk of death in the period shortly after breaking your hip, it's just, you know, it's eye watering. It's a really scary thing because you go into hospital. You lose a load of muscle mask because you're sat in a hospital bed for, you know, days or weeks on end. Then you come home and you're less mobile at that point as well. So you're at higher risk of a second fall.

and these things all sort of compound into each other. And it can mean that having a lower muscle mass can actually have a really, really serious impact on your life. So it's just really important to maintain that muscle mass. But what we know is that this isn't strictly a sort of aging related thing. It's more a sort of lack of use related thing. And if you can carry on doing strength training, doing resistance exercises into older age, you can maintain that muscle mass. And that can hopefully keep you, you know, living healthily for longer. Are there any other ways that muscle can help your biological age?

I think some people might be thinking, how is just not falling down helping someone's biological age? It seems a bit more preventative. Yeah, absolutely. And I think there are a few different mechanisms that we can think about. The first is that when you have a meal, you get a big spike in your blood sugar. And people have probably seen a little bit about this on social media. There are all kinds of ideas of wearing these continuous glucose mites, miners of these spikes and try and choose foods that don't spike it. I'm not so into that sort of thing.

But what we do know is that muscle is probably the single, not probably it is, is the single biggest sink of glucose. So when you eat a meal, your muscle actually absorbs a lot of that sugar. And that means it's hugely, hugely important for your sort of broader metabolic health. We also know that one of the crucial processes that happen in aging. We're actually going to talk about this, I think, in a subsequent answer, is that aging drives and is driven. It's sort of this vicious circle by a process called chronic inflammation. So inflammation is the normal reaction that your immune system has. When you get an infection or if you get an injury, your immune system will rush to the side of the problem. It will kill all the bacteria, kill all the viruses,

try and help heal that wound, whatever the problem is, it will try and solve it. And then it'll die away as quickly as it sort of rushed to action at the beginning of that problem. And this is called acute inflammation. So this is rapid onset, rapid turn off. But unfortunately, as we get older, our immune system starts to become a little bit paranoid. It's sort of looking over its shoulder constantly. It's a low level activation of your immunity throughout your life. And what that seems to do is accelerate the whole of the aging process in a variety of different ways. And it can drive cancer. It can drive increased risk of heart disease. It can drive dementia. And actually we think that muscle that is moving, you know, that's being moved,

that's exercising, gives out anti-inflammatory signals, whereas muscle that's static, you know, if you're sedentary at home all day, then that tends to drive inflammation. And so although we aren't fully sure of the mechanism, that really does seem to be one of the central pillars of slowing down your age, is trying to keep control of your inflammation. And one of the best ways you can do that is to exercise that muscle, keep it moving. And actually, there's sort of growing evidence that it's not just about exercise sort of per se, it's not just about going out for a run or going for a swim or whatever your preferred form of exercise is. It's also about staying mobile throughout the day, just having a continuous motion and not being sedentary. I'm not sure if this is taking

it a little bit too far, but some scientists argue that if you go out for a run in the morning and then just sit on your bum at your desk, you know, typing at your computer for the whole rest of the day, you basically cancelled out the benefits of that run. I think that might be taking things a little bit far, but nonetheless, I think it is worth, you know, trying to get up once every half hour, once every hour, just do a few steps around the office, around the house. It can be more difficult if you're working enough, you can look like a bit of a crazy person going for a walk around the desk. But I do think it's really important just to keep those muscles moving because there is evidence that being sedentary can drive ageing can drive inflammation. And I think it's definitely

worth sort of trying that out to try and slow your aging down. Ambition comes in all shapes and sizes. At First Citizens Bank, we roll with your goals because we're built for what you're building. Fit for your ambition for Citizens Bank. It's peak pollination season, and my business is scaling fast. To keep the nectar flowing, I need a phone plan with top priority data speed. That's why I chose GoogleFi Wireless. My connections stay strong even when the hive is buzzing. Plus, unlimited plans started $35 a month.

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Today, in partnership with French acoustic specialist focal, name audio creates systems that deliver exceptional sound and unforgettable listening experiences at home. Try it for yourself at a focal powered by name boutique. Visit focal powered by name.com for more information. Why we're on the topic of exercise, I should probably ask, is there a better type of exercise when you're talking about having muscle is quite good for your biological age? Should everyone be hitting the weights every day?

I think the best type of exercise is the exercise that you'll carry on doing. And I know that sounds like a really boring answer in a sense. But if you're not able to leave yourself out of bed in the morning to go for a run, maybe morning runs are not your thing. Maybe you'd rather go for a swim in the afternoon, or maybe you'd rather go for a cycle in the middle of the day in your lunch hour or something. It really doesn't matter as long as you're trying to, for the sort of cardiovascular side of things, hit something like 75 minutes of vigorous exercise or 150

minutes of moderate exercise. That's more sort of a brisk walk than a run type thing per week. And I think that's just a really important target for everyone to try and, you know, hit or perhaps even exceed. When it comes to the resistance training, I think it is important to try and do something in order to put resistance against your muscles and that then also strengthens your bones as well. I think to an extent that probably does mean hitting the weights more than, you know, most of us do. There are still things you can do at home. You can still do press up, which you can still do body weight related exercises. So you don't necessarily have to be pumping that iron. But the really important thing is to be putting that strain on your muscles and giving the signals to your bones,

actually. We know that when you're doing strength training, your bones feel that sort of pressure going on and that causes them to strengthen. So that's another thing that happens with age that is possible to, you know, potentially partly reverse by doing this kind of exercise. I think we're going to have to talk about someone's diet. So how can someone change their diet in order to sort of live longer? What sort of things should people be eating, for instance? I think diet is just like perhaps the thorniest issue on the internet. I honestly think that we're going to have cured aging medically before we fully understand everything about diet because there are just so many variables. There's what you eat, there's when you eat it, there's how much of it you eat,

there's the ratio between the big stuff, the proteins, the carbs, the fats, then all the small stuff, the nutrients, it's an absolute mind-filled. I think the sort of practical guide for most of us today is that probably most of us could do with eating a bit less meat. You know, that sort of plant-based sources of food tend to be healthier for us. They're also healthier for the planet as a sort of additional beneficial side effect. We think that, you know, getting more plant protein is important. So that's things like, you know, pulses, leumes, legumes. I've never quite sure how to say that word. Nuts, that kind of thing to replace the animal protein that you're perhaps losing out on.

Lots of green veg, lots of fruit. You know, these are all things that are definitely very beneficial for our health. Then we come onto the more sort of trendy, you know, faddish stuff that people often talk about. And this can include things like time restricted feeding or lasting. That's something that's often talked about online today. And the evidence for this is just, it's frustratingly piecemeal. I really feel like this was one of the most annoying parts of the book to research, because you always feel like you're just one more study away from fully understanding it. And then you read this next study and your whole sort of worldview switched on its head another time. So this work actually started in the 1930s when a guy called Clive McKay, an American

scientist, was really interested in the development of rats, depending on how much food they ate. And so you got a couple of different groups of rats. One group was allowed to to eat as much as it wanted. And the other group had its calories, sort of the bulk of its diet cut back by about 50%. But crucially, he made really, really carefully sure that he got these rats that were eating less to get all the micronutrients things, all the vitamins, all the minerals, that sort of thing. And this is sometimes called calorie restriction with optimal nutrition or cron. What he found was that the rats that were eating less lived about half as long again as the rats that could eat what they liked. And not only that, you weren't dragging out the period of

frailty at the end of life. It's not as though these rats were so hungry they couldn't even summon the energy to die. It was reducing their risk of disease. They got less cancer. They got fewer heart problems and so on. They did little autopsies on the rats after they died. And they found that the calorie restricted rats actually looked very, very similar to the rats that had died 50% sooner who are eating the normal diet. So what does this teach us for human beings? Obviously, we aren't rats. What's really remarkable is this research basically lay fallow for about 50 years, which I think is because when Mackay was doing this, this is at the birth of nutritional science. You've got to remember life expectancies in countries like the UK, the richer

countries in the world, probably 50 or 60 years old. So people are much more interest in how to get optimal nutrition for children, how to make sure that kids grew up healthy than they were at the sort of later end of life that perhaps is more of an issue today. So these research results really weren't followed up. But come the 70s and 80s, people did sort of uncover this stuff. I think, wow, this is fascinating. It's a way to essentially slow down the aging process by this shockingly simple intervention. And we've since found that it works in yeast, so that's the single-celled fungus used for baking bread and brewing beer,

in nematode worms, in flies, in mice, in dogs, in guppies, in water fleas, just this incredible range of animals in dogs. There's even some evidence it might work in monkeys, and I can talk a bit about that in a second. What this seems to be is this incredibly almost universal ability to slow down the aging process. So the obvious question is, does that work in humans? Let's have a quick think about the monkey study. I say monkey study, there are actually two of them.

And these were done at two separate locations. And one of them found that the monkeys did live longer when you restricted their diets. And the other found that it didn't seem to make a lot of difference. They perhaps lived a bit healthier for longer, but their overall lifespan wasn't too much changed. And to summarize what could be, you know, an hour long scientific debate, probably more, if you've got a couple of calorie restriction enthusiasts to have a chat about it. It basically seemed that the monkeys that are eating a healthier diet to start with. If you restricted that healthy diet, it didn't seem to make a lot of difference to their lifespan.

But in the other experiment, the monkeys were eating what could be characterized as a less healthy diet, sort of higher in fat, higher in sugar, that sort of thing. And restricting that diet did seem to have a bigger benefit on lifespan. And so the lesson from this may be, and perhaps I'm over extrapolating here, because I hate restricting my calories. I'm hungry. I get hungry. But the lesson here seems to be that if you already eat a basically healthy diet, there's not a great deal of benefit to restricting it. We have done some really short-term studies in humans. So there was a study called calorie, which is a tortured acronym that I've forgotten.

But nonetheless, they got people for two years and tried to get them to eat 25% fewer calories with optimal nutrition. What they found was that people couldn't stick to it. They actually managed to cut back the calories by 12%, which is still quite an impressive feat if you can maintain that for a full two year period. But what they found was this did seem to result in improvements in health. But the people reported the hunger never goes away. You might think you get used to eating less. You don't. People reported feeling cold all the time.

A few people had to drop out of the study because their bone density or their sort of the thickness. of their blood dropped and so those were, you know, considered warning signs for general health. So this is probably a diet you shouldn't be trying, you know, without at least a bit of medical advice, a bit of help. It does seem to improve short-term health? The real question is, does it improve long-term health? Because we've also got evidence that eating dramatically less calories all the time can reduce your immune function. And maybe this only works in rats or mice in the lab because they're in this costed environment. They don't really have infectious diseases, whereas we're walking around, you know, having just come out of a global pandemic, would I want it to be

calorie restricting during COVID or would I want to be calorie restricting now during the winter flu season. There's no point theoretically living forever because your aging's been slowed down if you get struck down with the flu age 40 or 50 or 60. So it's clearly a lot more complicated for people. It's also just, as I said, really hard to stick to because of all these side effects. So this ultimately, and this has been a very, very long answer for which I apologize, but this is how we ended up with the idea of fasting because it's so, so hard to stick to the pure calorie restriction. Maybe we, instead of eating less all the time, could just not eat anything for two days a week, two non-consective days a week. This is the sort of five-two diet. Maybe we could do time-restricted feeding,

where we only eat in an eight-hour window during the day and then fast for 16 hours. Maybe we can recapitulate some of those benefits. And there is some sort of putative evidence for that in animals. So when you do the calorie restriction experiments in mice, for example, mice are actually nocturnal, which means they're mainly active during the night. But obviously, PhD students who are the ones who feed the mice, they are diurnal, they're mainly active during the day. And so with the way that these animals are normally fed, the animals that can eat what they like obviously just have a massive pile of food, which they can access at any time. But the animals that are on a calorie-restricted diet, typically the PhD student will go and feed them this food right at the end of the day, the end of

the PhD student day, which is, of course, the beginning of the mouse night, because that's when they're metabolically active. And these mice, they're being calorie restricted, they're starving, so they chow down on that food, they might gobble it all in the first hour, and then they fast for 23 hours. So is this an experiment in calorie restriction? Or, or, is this an experiment in intermittent fasting? And frustratingly, scientists haven't really managed to tease out the difference between those two things. I actually tried time-restricted feeding, which is this idea of the 16-8 diet where you only eat during an eight-hour window. And this is surprisingly easy. Like I don't find it too difficult to skip breakfast, you know,

have your first meal at lunch at noon or something like that, and then you're only allowed to eat until 8 p.m. Then you have to fast for the rest of the time. It's surprisingly, you know, straightforward to do. But literally the week that my wife and I started doing this, a study came out showing that time-restricted feeding, which in this context was being used for weight loss rather than an anti-aging thing, it did cause the participants in the trial to lose weight, but they seem to preferentially lose muscle mass rather than fat mass. And we've just been talking about the huge importance of maintaining your muscle mass into older age. So we unfortunately stopped that time-restricted feeding experiment about a week after we'd started it.

We just need better, longer human trials. And I think for most people, and as I said before, there's a bit of a risk of bias, but it might come as a relief to those of you who like me get hungry. the best thing to do is just to eat a balanced diet, you know, mainly veg, not too much meat, and just sort of try and maintain a healthy weight. And those are the key key takeaways from, I think, current cities of diet. Do you think someone could try the 16-8 fasting, but also just be doing a lot more strength training to compensate? That's something that needs to be looked into, I think, because, you know,

there's definitely a signal that you get from strength training that causes the muscle to build. There might also be a way of increasing the protein intake of people doing the 16-8 diet, and then that will allow that to sort of offset the effect. I think we just don't know, and more experiments need to be done. But as I said, the sort of frustrating thing about this is, as soon as you start to delve into it, there are just so many variables. I think if I had, you know, a million dollars to spend on aging research, I wouldn't spend it on trying to optimise a 16-8 diet.

I'd spend it on, you know, trying to develop a new drug. That means you don't have to worry about what we eat. Is there any other lifestyle changes which you think people could easily make? So, for instance, is there a relationship between sunlight and aging? I think a lot of people would assume yes. Yeah, and actually, so this is the, I said right at the start, about five questions ago, I'd split this advice into two categories, right? And this is the second category. This is the category where it's things that you wouldn't necessarily think are aging related until you

understand the biology. And so not the obvious advice, but the sort of less obvious stuff and understanding of aging biology illuminates. And I think sunlight is a really interesting question. And I've actually become someone who's quite a militant sun cream wearer as a result of the work that I've done looking at aging. And there are a few different reasons with this. The first and the obvious one that most of us have heard of is skin cancer. And that's obviously caused because the sunlight, the ultraviolet rays in sunlight particularly damage your DNA, they can be a cause of those mutations that we were talking about earlier that can put a cell on the path to becoming cancerous. And obviously your skin is all over the surface of your body. I hope that's not a too obvious

thing to say. But it's therefore exposed to all of this UV radiation in the way that your inids aren't. And so we know that skin is one of the most highly mutated tissues in our bodies. It's like, you know, it's much, much more mutated than anything else. And so therefore it's a huge risk of potentially getting skin cancer. But the other problem is, I know that if you're going to an experiment, you can sample the skin of someone who's aged, say, 50 years old. And what you find is, even if they haven't got a skin cancer, there is basically not a single unmutated cell in their skin. And the reason is that you can get a mutation that isn't necessarily cancerous per se, but it causes those cells to be better at dividing, to better at reproducing in your skin.

And that means that those cells, it's like evolution, essentially, they're going to out-compete the cells that have unmutated DNA, because they're going to divide fast. They're going to divide more. And what you find is that if someone's, this process starts very early in life. And by the time you're in your 40s or 50s, basically your entire skin is this patchwork of mutant clones, which sounds quite terrifying. We don't exactly know what the impact of that is on something like inflammation or something like the broader aging process. But what we do know is you're not born with that, you know, like young people, people who have a low risk of dying simply because they're young, haven't accumulated all of these mutations.

And so I'm taking every step I possibly can to reduce the rate at which these mutations are accumulated. And so I think actually the best advice, by all means go out and get sunlight. I think it's nice. It's not something that should be avoided. But make sure that you try and cover up. If it's some, you know, if you can wear long sleeves, that's good. If you can't wear long sleeves or stay in the shade or whatever it might be, I wear sun cream almost all year round. Unless it's a really, really, you know, gray winter's day.

I think it's just worthwhile slapping some of that stuff on to reduce the cancer risk and to reduce the risk of these kind of expansions in our sense. skin, even though we aren't 100% sure what exactly they might mean from an aging perspective, I'm willing to bet it's not good. And then what that means as a sort of supplementary thing, literally supplementary thing, so I did here, is you're not going to get the vitamin D that you need, because the way that our body generates most of its vitamin D, it's very hard to get it through the diet. You can get it in fish, and there's, you know, there's a few other sources, but basically most of us don't eat enough vitamin D to fulfill our requirement. Then means the normal way to get it is by UV generating that vitamin D in our skin.

So if you're wearing sun cream or if you're basically covered up the whole year around, you're not going to get that vitamin D produced in that way. And so what that means is I think it's probably worth popping not a megadose, but a normal sort of recommended daily allowance level of vitamin D in order to make sure that you're not falling short on that. On the topic of sun cream, I do have to ask, how strong would you recommend people wearing? And are you wearing some right now as well? I actually am, yeah, even though it's a great winter day in Berlin. I just feel like you've got to be careful because this UV is a cumulative process, right? So although it's a very very, very low instance that I'm getting today. I think probably today you don't need factor 50

on a day like this. But I think, you know, sticking on a bit of factor 15, even in the winter, because the other thing is, when you look at the factors on these sun creams, they tend to assume that people apply them in a very specific way that's sort of prescribed by the manufacturer when the testing's done. It's far more than most people apply. You have to apply out. You know, what feels like globs and globs of this stuff to hit the manufacturer's requirement. And that means that if I'm putting on, you know, a light coating of factor 15, I'm probably only getting factor seven, factor eight or something like that. So therefore, I think for, you know, for most of us, it's really important just, you know, try and apply a little bit all year

round. I think when you're going out and if you're skiing in the winter, but if certainly if it's the summer, you want to be putting on a higher factor, factor 30, factor 50 are not crazy factors to be sticking on because, again, it's just this cumulative thing and it doesn't block all of the UVs. If you're going to be out in the sun all day potentially, then I think it's just really important to put on, you know, nice high factor, keep reapplying it. And I know that all of us aren't perfect. We don't put on enough. We don't reapply it every two hours as per the manufacturer's instructions. So I just always tend to err on the side of a higher factor to compensate with the fact that I am a flawed individual like all of us are. Are there any other behaviours

which you've adopted since reading up so much about aging? Something that I definitely become a bit more fastidious about is oral hygiene. And that might sound like a slightly bizarre thing. What was brushing your teeth? What was having a clean mouth got to do with how long you live? And this is another one where actually understanding the aging biolids. You really illuminates something that you wouldn't necessarily have thought of. The first studies about this came out in the 1990s, and they were these observational studies. So they'd look at people in the population, see what they were doing and see what their health outcomes were. And they found that people who had better oral health seem to get fewer heart attacks. And what a lot of listeners will probably be thinking

right now is this is a case where correlation doesn't necessarily equal causation. There might be some third factor that isn't properly captured by the study. So for example, it might just be that people who are health conscious tend to brush their teeth really fastidiously. They also to eat well, they also tend to exercise, and so they're getting fewer heart attacks because they're eating well on the exercise, they also happen to have, you know, cleaner teeth. And that's definitely a problem with all observational studies like this. But as we've understood a bit more about the biology, we think that the sort of key linking factor between oral health and health of the rest of the body is this chronic inflammation that I described earlier. And the reason is,

when you have gum disease or when you have tooth decay, that fight with the bacteria that's going on in your mouth, essentially, can never be won by your immune system. And that's kind of the reason, actually, that dentistry is in some way so medieval, because they literally drill bits out of your tooth to try and get rid of this infection, because your immune system can't win that fight. And so what that means is there's constant sort of fizzing and buzzing of inflammation in your mouth. That is essentially, you know, chronic inflammation caused by this process. And we think that that is then what drives the risk of heart disease,

might even drive the risk of dementia. There's been some evidence where people have found the bacteria that cause gum disease in the brains of people with Alzheimer's. Now, again, correlation causation. is it that the bacteria are taking advantage of the disease brain to sort of scurry in there and set up shop, or is it that those bacteria are somehow involved in the sort of the process that causes the dementia? We don't know the answer to that yet. But I think that's enough evidence for me to definitely be brushing my teeth, flossing, seeing the dental hygienist regularly,

getting any dental work that needs to be done, done, and so on. Not just to avoid, you know, painful tooth decay, but also to hopefully prolong my healthy life. That was Andrew Steele, author of Ageless The New Science of Getting Older, without getting old. If you like to hear more from him, check out our next episode of Instant Genius out next week, where we'll discuss the anti-aging wonder drugs

just around the corner. Be sure to also check out Andrew's YouTube, Instagram and TikTok pages and also his latest feature on anti-aging for BBC Science Focus magazine, available across our digital channels. As always, this episode of Instant Genius was brought to you by the team behind

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