191: Can We Live Longer? What it Might Mean for Medicine, Money, & Markets - With Dr Andrew Steele

25:24Dr Andrew Steele:And scientists did an experiment, I think it was published in 2018, where they got a couple of different medicines. There's something called asatinib, which is a chemotherapy drug, but they used it at much lower doses than you'd normally use it for cancer. And they combined it with a molecule called quercetin, which is often found in sort of colored fruit and vegetables, things like, you know, red cabbage and that sort of stuff, sometimes given as a supplement. And they found that by combining these two things together, it was very effective at killing the senescent cells. And they gave this cocktail to mice.

25:48Dr Andrew Steele:they found that it essentially made the mice biologically younger so it firstly made them live a bit longer which is a good start if you claim you're slowing down the aging process but it didn't drag out that period of frailty at the end of life it kept them healthier for longer too so they got less heart disease they got less cancer they got fewer cataracts which are the cloudy things in your lens of your eye that can can be one of the leading causes of sight loss as people get older um they were less frail so they basically send the mice to the gym in these experiments they've got little treadmills they've got little rotating rods that the mice have to dangle off.

26:16Dr Andrew Steele:And the mice that had these drugs, they were the same age as the other mice in the experiment, but they were running further and faster on the treadmill. They were able to dangle longer on these spinning little rods, little sort of crystal maze style challenges for the mice. They're just better at them. It seems to also have an impact on cognitive decline. So if you put a young mouse in a maze, it's very keen to run around, find the cheese, do whatever it is mice do in mazes. But if you get an older mouse, it's often a bit more anxious, a bit less willing to explore. And by giving them these senolytic drugs, they cleared out those senescent cells and they seem to rejuvenate some of that youthful curiosity and honestly these animals they just look great like i i actually never i was a computational biologist back when i was working you know in real science and i've never worked with a mouse in the lab you know i wouldn't know which end of it to pick up to be perfectly honest but you do not need to be an expert mouse biologist when you see a picture of these things side by side one of them's got you know thin fur it's got graying fur it's got little patches of missing fur or whatever the other mouse just looks like a younger animal.

27:13Dr Andrew Steele:It looks like it should be on the cover of Vogue, whereas the other mouse looks like it's aging quite poorly. So what this shows us is these hallmarks, for example, the accumulation of these senescent cells, they're fundamental drivers behind perhaps even all of the aging process, certainly a significant number of parts of it. And by targeting those early stages of the aging process before they become a problem, we could not treat cancer, but prevent cancer, or at least defer it until later in life. We can also defer the frailty the cognitive decline that wouldn't quite meet the threshold if you were being diagnosed for dementia the incontinence the impotence all of these things that come along that might not necessarily have a treatment you know sort of a way to deal with them in the medical system as it stands at the moment you know the wrinkles and the gray hair people are going to start taking these things for their heart disease and they might notice they start looking fantastic because it has these sort of other side effects these positive side effects which is not often something you know we're necessarily expecting out of medicines so they really do have the potential to change the way that we do medicine.

28:08Dr Andrew Steele:And even more exciting, there are now 20 or 30 companies trying to turn this from something that works in mice in the lab to something that actually works in humans. So this is something that's being invested in now. This isn't something that's 50 years in the future. And honestly, there are, you know, I've obviously given quite a long monologue there about that particular type of therapy. But we have, you know, I could give a similar monologue about maybe 10 or 20 other things that we think are promising aspects, promising sort of interventions in the aging process that work in mice. We just need to try some of these things in humans.

28:34Dr Andrew Steele:and, you know, who knows what the results might be.

28:36Mike Milken:So one other thing I'm clear on, Andrew, is had you been my biology teacher, I would have carried on studying it. Oh, wonderful. Now, let's talk about side effects. And by that, I really want us to laser in on the, you know, the economics for the ones of a, you know, for the ones of a sort of a simple high level term. We talk about in our market, the total addressable market, but let's just have a little sort of discussion about longevity economics and how we should think about it and putting some numbers on it.

29:04Dr Andrew Steele:Yeah.

29:05Mike Milken:I think you write in the book, or I've certainly heard you say that slowing the aging process by a year could be worth over$35 trillion. And for those who want a quick reference, that's over one year's US GDP.

29:19Dr Andrew Steele:Yeah. Yeah. These numbers really are remarkable. So let's sort of dive into that first. Actually, this is a number that's often quoted. It's from a paper by Andrew Scott, The Economist, and a couple of co-authors. And it's a study looking at the value of a statistical life. So this is a thing that's often used in policymaking around the world and you're trying to decide should we do a particular bit of road safety stuff or should we approve a particular medication at the end of the day these decisions are economic people often don't like to hear that but the fact is we've got limited resources you know what is economics if not the study of how we allocate limited resources so these kinds of decisions have to be made and so what they did was they looked at the value of a statistical life in various countries and the one they chose to highlight was the u.s and they said you know there are also these sort of these benefits that come along with slowing down the aging process because if you were to just extend people's life in ill health, then obviously that's expensive.

30:03Dr Andrew Steele:Those people, not only are they costing the system money in the sense of needing healthcare, needing social care, and perhaps needing to be supported at home, some of which could be by, you know, official channels in the sense that you have a paid care, you might move into a nursing home, but a lot of which is done by a sort of casual care economy where people give up work or go part-time in order to look after an elderly relative, which also has costs that come along with it. In fact, I think in the UK, that sort of casual care economy is estimated to be about as big as the NHS's government funding.

30:29Dr Andrew Steele:So it's a really remarkable scale it's like 100 over 100 billion pounds um they calculated if you sort of look at this if you have healthier people they then stay economically engaged they're gonna you know their consumption stays high they're not um costing the system anything or as much in terms of care and so the scenario they looked at was if we were to slow down aging by a single year what would that sort of be worth in this broad sense in this value of a statistical life in this willingness to pay framework so this isn't a sense in which us gdp is you know suddenly going to become twice as big this is looked at discounted in the long term what is this worth in the broadest possible sense to the economy and the number they came up with was 38 trillion dollars and that's just remarkable you know you don't hear figures like that every day there are not many interventions that we can talk about in the sort of global economic and policy sphere where those kinds of numbers are appearing and there's a sense in which that's a lowball estimate because that's that's slowing down aging by a year keeping people alive for an extra year and obviously healthy for that extra year as well.

31:23Dr Andrew Steele:They worked out, it basically went up linearly. So if they looked at a 10-year extension of healthy life, a 10-year slaying of the aging process, I think that was$367 trillion, which is just, you know, that's a large amount of money. And again, I'm not saying that that's the amount, that's not the total addressable market. That's not the right way to think about this. This is a willingness to pay calculation. But what it shows is it gives us an idea of the scale of the money that's sloshing around here. Like if you are able to access even a fraction of a fraction of that, and if a drug costs maybe a couple of billion dollars to develop, which is the sort of figure people throw around these days, there is still an enormous potential to make large amounts of money to improve huge numbers of people's lives, to sort of spread the positive externalities of this development throughout society to an enormous extent.

32:05Mike Milken:So, Andrew, when we just dig into those numbers, I think these are US numbers and they may be out of date. Cancer is costing nearly$280 billion, heart disease, 200 billion, stroke$110 billion. I mean, these are non-trivial numbers now.

32:20Dr Andrew Steele:Just sort of, how should we think about those? I think, so the first thing to say is, those are numbers that I've been using in my talk for a while. They are a few years out of date. But I do think, nonetheless, if you add up cancer, heart disease, stroke, and dementia, which are the four that are my sort of favourite, that's the wrong word, age-related diseases, that doesn't even capture the whole of the ageing process. There are many other age-related problems. There are the wider, as I said, things like the frailty, the cognitive decline that isn't necessarily bad enough to be dementia. These slow people down.

32:47Dr Andrew Steele:and they make them less economically active. They mean people suddenly need looking after rather than being able to provide services in the economy. So even if we're looking in this very narrow way, those four diseases cost the economy getting on for a trillion dollars. It's probably over a trillion dollars now per year. If you think about the US healthcare system, that's four or five trillion dollars a year. A huge fraction of that is chronic diseases of aging. And that's because something like dementia, actually you don't very often die of dementia. It's not necessarily in the top causes of death.

33:14Dr Andrew Steele:That's normally your cancers and your heart disease sort of statistics but it's very very expensive because people live with dementia for an awfully long time often until cancer or heart disease takes their life and they need very intensive care we haven't got very great treatments at the moment so there's not a great deal we can do and that means these figures again they're just enormous whatever way you cut this the economic cost of aging today or the potential of slowing down aging in future there are obviously different ways of looking at the same kind of thing and i think the way to think about this is to contrast it with the amount of effort we're putting in to try and do something about it um and to take the us as an example um the us has a an nia a national institute on aging and this is a government body a federal uh government body that is looking to try and you know do research basic research and applied research into the aging process now there are two problems uh that arise here the first is that there's this running joke in aging biology the nia actually stands for national institute on alzheimer's disease because of for various historical reasons that's where dementia research which is housed within the US system, it gets about three, three and a half billion dollars a year, this department.

34:19Dr Andrew Steele:But about two of those billions go straight to dementia. Now that's a very important disease. I'm not saying we should cut dementia research, but still this isn't the aging biology that I've been talking about today. If you look at what's called the division of aging biology within that, it gets about$350 million a year. That's a little bit north of a dollar per American. And that's remarkable given the trillions that are on the table here. and the fact that aging causes 85 % of American deaths because if you add up the cancer, the heart disease, the stroke the increased risk of dying from an infectious disease as you get older if you do all that stuff you get about 85 % in the US actually the US is a bit of a laggard in terms of high income countries over here in Europe I think pretty much every country is over 90 % of deaths are caused by aging and the reason that I chose the US as an example is I'm not aware of a European country or the UK that has a National Institute for Aging equivalent so to take the UK here, West Satin as an example we have research councils we have a biology research council we have a physics research council they're sort of split up by subject area there's not this sort of mission orientated feel in the way that research is funded over here um and so i actually you know i've written to the government and asked them how much do you how much aging research funding do you give out they just honestly don't know which is a political problem in itself because this is you know such a big deal we also need to be thinking about getting private capital and so there's this there's a slight myth that it's okay the silicon valley billionaires are all funding uh you know science and there are some high profile examples of that they they make a great media story if jeff bezos is sinking money into this this company called altos labs you're doing fascinating technology called epigenetic reprogramming which we can go into um but that company is worth between three and five billion dollars depending on the source that you read now bezos i haven't looked at what his net worth was this week depending on what particular gyrations are happening in the stock market but he's worth north of 100 billion dollars and we know he isn't the sole investor in that company so but even if he was let's say he invested three billion and he's worth 150 billion that's a couple of percent of his net worth and so he's not obsessed with longevity by any means like you know that's a maybe he considers that a savvy diversified part of his overall investment portfolio um and then you know the number of other billionaires who are really investing in this stuff probably under 10 globally and if you think about you know there are 3 000 billionaires in the world i think again depending on exactly what the stock market is doing on any given day um they're really not investing in longevity science.

36:33Dr Andrew Steele:So there is an influx of private capital. I think that's, you know, the sort of longevity biotech is increasing, but it's still only a few percent of overall biotech investment.

36:40Mike Milken:Well, you have a great grasp of the financial sort of, you know, equation, which not all scientists would have. But if you're sitting there and you're running a pension company, or you're sitting there and you're running an insurance company, what would be your one sentence of advice to each of those CEOs?

36:54Dr Andrew Steele:I think factor this in. I think that's something that really hasn't been very widely done. because what I'm talking about could all be moonshine. Science is like that. Science is, you know, you have to do these experiments. We have to try them out. I think it's very likely that some of this stuff is going to happen, but I cannot put my hand on my heart and say that even if we invest 100 billion in science, that I'm definitely going to get X years of life expectancy at the other side. The challenge is we live at a time now where life expectancy could be dramatically increased. We've got all these ideas that work in the lab.

37:21Dr Andrew Steele:And so if you're a pension fund, maybe you should be thinking, is there a 1 % chance that all my clients are suddenly going to live to 120? that you know 1 % isn't very likely but if it's that possibility and you're sitting on trillions and trillions of dollars in assets that you're trying to manage you're trying to work out how this pension fund is going to carry on into the indefinite future you need to be thinking about even these outside possibilities and one of the reasons this is less unlikely than it sounds because you know the oldest person in the world ever recorded lived to 122 and in fact no one else has exceeded 120 so you might be thinking 120 that's pie in the sky and this is science fiction let's think about the sort of timeline of the development of these drugs so we've already talked about senolytics i think there are maybe five or ten other categories of drug rapamycin i mentioned earlier as well um which are drugs that we've shown work in the lab they often have a precedent in human uh treatments because at the end of the day scientists they're publicly funded they often can't afford the most cutting-edge stuff so they've tried a bunch of drugs that we've had often sort of in the back of the closet they're out of patent they've been around for decades we've tried them in mice we've demonstrated they slowed down the aging process these are safe enough and well understood enough that we could try you know we could start a human trial today if someone you know handed me a hundred million dollars um which again tiny amount of money considering the potential benefit there um and say we did 10 of these trials i would be absolutely astounded if we didn't get at least a year of extra healthy human life so we've got these ideas that could work in humans um and five years is the sort of time scale we need for these trials so if you're alive today and you've got five years of life expectancy ahead of you you could be around in time for the first generation of longevity drugs now these aren't going to get you to 120 i'm pretty sure maybe i can put my hand on my heart and say that i'm pretty sure but if you're let's say the average person on earth today is under 40 that means you've maybe got 40 50 years of life expectancy ahead of you if nothing much changes um what then happens is you're around in five years of course for the first generation of longevity drugs that means you live a little bit longer scientists might have 50 years in the future now to develop whatever the next round of treatments is and maybe in 10 20 years time we've got ideas for things like gene therapies for longevity.

39:21Dr Andrew Steele:Now, these aren't things that I'm expecting to be around next year, but we've had some amazing stories in the news just this week of, you know, gene therapies being given to children with very, very serious, life-threatening, lifelong conditions. And as we cut our teeth, trying out these things in really serious conditions where people are at the end of the day, prepared to take a risk on, you know, experimental new treatments. We're going to understand the safety, we're going to understand how to make them effective, we're going to understand how to make them cheaper. In fact, you can deliver gene therapies using the same technology that was behind the mRNA COVID vaccines and they cost a couple of dollars per shot to produce um so you know the production costs on these things are very very small and if we can do gene therapies for longevity which are a potential thing you know we've we've discovered a gene in an Amish population in the U.S.

40:01Dr Andrew Steele:that makes people live 10 years longer um again there are lots of caveats with this maybe you have to be living an Amish lifestyle that maybe this doesn't generalize but we have loads of genes in animals that provide you know comparably exciting changes in lifespan would I bet against there being a longevity gene therapy in the next 10 or 20 years i probably wouldn't because the technology is advancing so fast it might not happen but if you've benefited from that first round of longevity drugs in five years you're almost certainly going to be around in time for the 10 or 20 year timeline on the gene therapies and the stem cell therapies and the more advanced stuff then ai is going to start crunching lots and lots of data and understanding the aging process in new ways and develop the next round of treatments and so on and so we do not need aging to be cured next week in order for people to make it to 120 you can sort of slowly push your funeral back into the future and it might be that someone who's age 40 today has a decent shot of making it to 100 or a decent shot of making it to 110 and if i was a pension company i'd be trying to model this in a slightly more serious way than i've just sketched out there and say you know what will happen to our balance sheet if there's a small probability

40:56Mike Milken:that some of this stuff actually comes to pass i think the lady in france who you may have referred to who lived to 120 was allegedly interviewed by a not surprisingly younger reporter and he said well i hope we're around to do it next year and she looked at him and said well you look quite

41:09Dr Andrew Steele:healthy to me she was told to quit smoking by her doctor and then outlived her doctor in spite of continuing to smoke until she's in 110 so she had some good genes we have a section of these

41:26Mike Milken:interviews which we call the outsiders inquiry where we get interesting questions and in fact the team around the money is podcast have been very keen having rachel burke to ask you some questions so i'm actually gonna get out of my chair and each in turn is going to come and ask you a question or two. We're going to see how that works because it might endanger my permanence in this chair after this interview. So we're going to start off with Maddie Campion. All right. Okay.

41:49Dr Andrew Steele:I would love to know, is intermittent fasting worth the hype? And can you clarify the differences between men and women? Gosh, nice, small, simple question to start with. So intermittent fasting, I think the evidence is still a little bit out there i think that to the extent that it causes you to eat less it can be a useful way both to lose weight and potentially to live longer but the challenge is the evidence is frustratingly piecemeal so we've actually known the first ever longevity intervention that we knew could make mice and rats live longer uh was discovered in the 1930s it's what's called dietary restriction this is where you cut back what animals eat all the time rather than you know fasting a certain number of days of the week they just eat less every single day and it was discovered by a scientist called clive mckay working in the us that rats fed about 40 less live about 40 longer and again as a sort of recurring theme with these aging biology interventions they stay healthier for that extra lifespan as well so that's super exciting and scientists have since discovered that works in loads of different species um so again you know the worms the flies the mice the classic um experiments that are done but also things like water fleas and there's even been an experiment in dogs that suggests that this works uh there was actually a couple of experiments done in monkeys that showed that maybe a calorie restriction can work in them and the outcomes are slightly complicated so it maybe suggests that it gets less effective as you approach humans in sort of lifespan and complexity but there is really an interesting signal there that it might keep you healthier for longer the question then is is fasting you know an easier way to do this because i don't know if you've ever dieted i've tried dieting uh once or twice in my life and it is hard yeah it's really hard i i find that when i

43:28Mike Milken:do i've tried fasting and i just always feel so faint in the morning and i'm like i need to eat

43:34Dr Andrew Steele:but i think other people really benefit from it yeah and i think there's there's an element of that is it becomes a bit of a personal decision it's like whatever works for you if this is a way that you can eat a healthy quantity and a healthy diet and that's part of that constellation it can be useful but the challenge is we haven't got great evidence for humans so that there has been a study called calorie and i can't remember exactly what that stands for it's a tortured acronym where scientists like worked their way backwards from what they wanted it to be um they they tried to get people to eat 25 less for two years um and what they found was firstly people didn't manage that even though these were being heavily supervised really helped by scientists they only managed to cut their calories back by about 12 they did notice that these people got healthier in a variety of ways their blood test results improved in the sort of direction of good health but it was only a two-year study so we don't know if they were going to live longer and this stuff also comes with side effects so for example it's thought that eating less can reduce your immune function for example it can get a couple of the people dropped out of the studies because of anemia so they had two little iron in their blood it wasn't carrying enough oxygen uh their bones might thin these are all side effects you'd rather not have and it might be that you know maybe it makes mice live longer in a perfectly controlled environment in the lab but we're a human we're you know where humans are out here in the messy real world we're coughing and sneezing on each other we're getting infections sometimes we fall over and you know if our bones are thinner they're going to break and that can often be a start of a downward spiral as an older person i just don't think we have amazing evidence as long as you're eating a good balanced diet and not getting too many of those burgers and fries and soft drinks and whatever um that's going to get you 90 of the way there and that calorie restriction that intermittent fasting if that's what works for you if that's what allows you to maintain a healthy weight if that's what allows you to stay healthy in other ways that's useful but i don't think everyone should think you know this is some magic key to living to 120 and actually what we need to do is more science to develop uh pills like rapamycin that can simulate the effects of fasting and have some of those beneficial biological changes but without being hangry all the time

45:21Mike Milken:i would love to know what three things can someone in their 20s do to help them live longer

45:29Dr Andrew Steele:so i think starting healthy habits early is a really useful thing to do i think it you know the obvious stuff is don't ever take up smoking that's it's it's kind of so obvious it often doesn't go it often isn't said but if you do smoke and you're already in your 20s or 30s actually quitting can more or less eradicate the fact you ever smoked from your biology your body will return to that normal so if you're if you're 13 you're smoking you're thinking you know it's too late i've already started you can actually gain most of the 10 years that you would otherwise have knocked off your life and healthy life back by quitting early in fact even if you're 60 if you quit that year i think you add about another three years to your lifespan even by quitting at that very late stage so it's never too late to stop a bad habit like smoking um but then eating well exercising and i think you know quite a lot of the the sort of expected things to do i think the single biggest impact you can have though and this is quite a strange counterintuitive piece of health advice is actually to campaign for more funding for longevity science because you're young enough i'm assuming you are in your 20s that you're going to be around in time to benefit for some of these treatments most likely in terms of something slightly less conventional because i think a lot of what i could tell you you probably basically already know although we can drill into the details of exercise or diet or any specific things if you want brushing your teeth is actually very important this is something i wish i'd been a bit more attentive to in my 20s sort of dental hygiene not drinking too many sugary drinks i used to drink a lot of orange juice and i wish i'd paid a bit more attention to that.

46:45Dr Andrew Steele:The reason being, back in the 90s, we did these studies where it looked as though people with worse oral health, so more tooth decay, more gum disease, that sort of thing, went on to have more heart attacks and more other problems later in life. And the problem at that stage was, this looks like a classic case in science where correlation doesn't equal causation. So it might be that if you've got poor oral health, it's because maybe you're poor, financially speaking as well. Maybe you've got less time to exercise, you're not eating such healthy food, you've got this constellation of bad health behaviors and as a result that means that you're living shorter you're living less healthy not because of your um unbrushed teeth but because of the other sort of health behaviors that come along with that however we now know there is a link and that link is inflammation so this is actually one of the hallmarks of aging is this sort of deregulation of the immune system as we get older as we get older our immune systems get paranoid they start um you know seeing threats that aren't there they sort of start running around um you know shaking their fist at clouds basically and that biological process causes accelerates aging throughout the body.

47:41Dr Andrew Steele:And chronic inflammation, this sort of low-level paranoia, even when you haven't got an infection, even when you haven't got something that needs dealing with by the immune system immediately, is one of the drivers of the aging process. Now, if you imagine having tooth decay or having gum disease, these infections in your mouth, basically they're caused by bacteria in your mouth. The reason, or one of the reasons dentistry is so archaic, they literally drill bits out of your teeth, it's almost medieval the way that they deal with our mouths at the moment, is because your immune system can't get on top of those infections.

48:10Dr Andrew Steele:Those are sort of chronic infections in your mouth. And so your immune system is constantly fighting. It's a background of chronic inflammation. And we now know that's the connection. The molecules these immune cells are secreting can increase the aging of your heart. They can increase aging throughout the body. And we've even found some of the bacteria responsible for gum disease in the brains of people who have dementia. Now, we don't know which way that causality runs just yet. We're still trying to understand it. It could be that the bacteria are sort of taking advantage of the diseased brain and sort of using that as a chance to break and enter or it could be that some of those bacteria making it from your mouth through the bloodstream going up into the brain are one of the things that drive that dementia process and that's evidence enough for me to pay more attention to what i think is sometimes a bit of a neglected part of our health and make sure i brush my teeth go to dental hygienist regularly and so on okay so when researching the book uh what were the sort of top three fun facts which surprised you about longevity oh top three fun facts i think it's it there are just some amazing stories in this science um i think one of the most amazing is the story of the discovery of rapamycin so this is a drug that i've mentioned a couple of times before extends lifespan in loads of different animals in the lab um and this is a drug that was discovered on easter island so it's the island of the massive stone heads and uh the reason it's called rapamycin actually is because the name of that island in the polynesian the local language is rapanui so it was named after the island it was discovered on um this story is just bonkers from start to finish it started in 1965 when the chilean government who owned uh who own easter island decided they were going to build an international airport and this island had been isolated in the yes it's one of the most isolated islands in the world it's thousands of miles into the pacific ocean um and so the canadians were looking at this thing this is fascinating this has been this isolated community for thousands of years can we go and collect some samples find out what it's like before western civilization and tourists come and pollute it thanks to having this international airport so they sent down a naval expedition to collect samples of the people of the island of the environment and so on and during this time um there was actually a revolution on the island the people of the island weren't very happy about this international airport being built and so on and there ended up being it was bloodless thankfully but there was you know there was a lot of sort of fighting and protesting going on and the guy who eventually became the mayor of the island at one point hid out in the scientist's camp and escaped dressed as a woman in order to avoid being avoid being caught incredible story but one of the soil samples they picked up during this trip had some bacteria in it which later were analyzed and it was discovered the bacteria had antifungal properties and a scientist in canada worked this out and thought it could be an amazing fungal treatment and so he gave it to one of his neighbors actually had athlete's foot got rid of the athlete's foot but they later discovered that it didn't just slow down fungal cells from growing it also slowed down many many other kinds of cells including human cells and so he thought this is going to be potentially an incredible cancer treatment if we can slow down the growth of cells it's going to be a really big deal but for various reasons he just couldn't make it work and ended up that the pharma company he was working for shuttered that program but thankfully he was very persistent he took home some of these bacteria put them in the freezer put them in an ice cream tub wrote do not eat in massive letters sellotaped it all together sellotaped the freezer together and then when his lab was relocated from canada to the u.s he essentially smuggled drugs across the canadian u.s border as part of his removal process eventually managed to convince his bosses to reinstate this program and they did so and it turned out rapamycin is now an approved cancer therapy it's also an approved immune suppressing therapy for people who've had a transplant it's also if you have a stent insert so this is one of the things they put in your arteries after you've had a heart attack and try and expand the artery back up again they're often coated in rapamycin as well to try and keep the artery open for longer and then it was discovered in 2009 this paper came out that showed that it slows down aging in mice so if that's the final outcome of this incredible sort of laborious ridiculous story it gets us to that point and that could be the first anti-aging drug that's ever proved in humans i thought that was just absolutely incredible okay i've got another question um could we ever have a test which works out approximately when you're going to die and therefore that could shift retirement ages uh to be dynamic so they say you're going to die at 90 you can retire at 80 you know you're going to die at you know so it's that kind of a new sort of policy experiment based off this approximate hypothetical test so i think on a on a sort of broad population level, that's actually a really good idea.

52:26Dr Andrew Steele:And Italy, for a while, has implemented a retirement age that's pegged to healthy life expectancy. I think it's pegged to overall life expectancy, but the ideal for me would be pegged to healthy life expectancy. And I think that would, firstly, you know, governments obviously target GDP. That's a very well-known figure. They very rarely target life expectancy. And if, you know, if GDP goes down, the Bank of England gets involved, you know, everyone in the economy is trying to work out things to do about it. There are policy levers that can be pulled. If life expectancy goes down, we don't really have a directed policy response and i think it'd be fantastic if governments had a legal mandate to you know have that as a target as part of this sort of broader economic and health and well uh sort of wellness of the population indicators i think that'd be a fantastic thing in terms of for individuals i think i can see some ethical issues with the way that might be applied but we actually already do have such tests so there was a test that was developed in uh 2012 2013 called an epigenetic clock and uh so your genetics your dna the sort of instruction manual inside your cells.

53:21Dr Andrew Steele:And if you imagine that analogy, the epigenetics are then the sort of notes in the margin, the little post-it notes, the sticky things, you know, the underlines you've made, telling the body which genes, which part of your DNA to use, and which cell at which time. So that's a dynamic thing that changes depending on the conditions, depending on which cell it is in the body, depending on the time of your life. And we found that initially in 2012, 2013, when they were first developing these things, they trained them against chronological age. So you could get someone's epigenetic data, and you could predict how old they were to within four years.

53:50Dr Andrew Steele:Now that's interesting, but we do already have a technology for that. It's called birth certificates, and it's much, much less laborious and much more accurate than plus or minus four years. But the question is, those people who've got an older epigenetic age than their birthday, you know, candles on their birthday cake age, so to speak, are they at increased risk of death? Are they at increased risk of disease? The answer turns out to be yes. So you can have an accelerated epigenetic age, which means you're older than your birthday cake candles, or you can have a decelerated epigenetic age, which is younger.

54:16Dr Andrew Steele:Now, these things were first trained on chronological age, which isn't really the right thing, but there have since been other clocks that have been trained on time to ill health or even time to death there's a clock called grim age which is rather appropriately named that was trained on how long it was until people in this massive collection of patient data died and so you can use these things and you can predict people's dates of death reasonably accurately you know to within a few years with these clocks so whether or not we should use it for pension age i think is an open ethical question whether we should be thinking about using these things in screening in hospitals for example because you know it often becomes the case you go past a certain age you start getting colonoscopies or you start getting mammograms if you're a woman.

54:52Dr Andrew Steele:And so maybe we should be tying these things not to your chronological age, but to your biological age. Because we know, and I think this is quite intuitive actually, all of us know someone who's just turned 60, who's vibrant, who's still hiking, who's still working, who's still loving life. And someone else who's just turned 60 and they're haggard, they're wrinkled, they're maybe suffering from a couple of chronic diseases. It is very clear that we age at different rates. And so I think that's a very intuitive demonstration of the fact that biological age is a thing. And so if we can come up with ways to quantify that, and I think we are getting slowly better at that in the lab, maybe we should be using that to better deploy healthcare resources as well.

55:28Mike Milken:My question is, if you could go back to your early, mid, late 20s and change one thing about your life, knowing what you know now, in order to increase your health or your longevity, what would it be?

55:39Dr Andrew Steele:That's an interesting question. I think I've already mentioned I wish I'd taken better care of my teeth. I do wish I'd got a bit more into exercise earlier and particularly strength training at something I've just turned 40 and so I've really started like trying to be a bit more serious about going to the gym and lifting weights that doesn't have to be how you do strength training by the way you can climb there's all sorts of things you can do but just not cardio because I think that I've always found cardio very accessible you know I can just go out for a run I can jump on my bike I can you know sort of almost not quite but no equipment required whereas the gym I've always found a bit intimidating I know there are certain people who grow up in the gym and they're pumping iron from you know back at school or university days I think we've really come to realize that strength training is super important in the long term.

56:16Dr Andrew Steele:And it's all about building those early habits because I think when you're still in your 20s, you don't have too much to worry about. And thankfully, you know, you stay strong almost regardless of what you do. As you start to move into your 30s and certainly your 40s, you're starting to lose something like 10 % of your muscle mass every single decade. And that isn't going to really affect you in your day to day life unless you're lifting heavy things all the time until you're hitting your 60s, 70s and 80s. But you want to start from that higher base and you want to make sure you've got more of that muscle mass earlier in life.

56:42Mike Milken:Yeah, I've heard with strength training and also resistance training, it's also really impactful for women as they age because we lose a lot of bone density, especially if you've been dieting your entire life. And that really helps.

56:53Dr Andrew Steele:And the other thing is that I think after menopause, as soon as your ovaries start producing fewer hormones, one of the big impacts is that your bones start to get thinner. And we are understanding more, I think, about the importance of replacing those hormones as you get older. And that science is very much developing. And I'm very excited to see that because I think historically women have been quite neglected in medical research. but I think one of the really good things you can do we know that when you do resistance training when you lift heavy weights your body senses those heavy weights are being lifted and the two things it does is it you know builds muscle in order to try and make you more effective at that but it also feels that pressure in the bones and that does seem to sort of beef up that bone density a bit as well so particularly for women that's super important but also it's never too late and one of the things that really struck me a study that I found while researching the book they got people in their 90s and they started them on a strength training program and this probably isn't you know what you and me are imagining pumping in the gym but through this strength training program over the period of a couple of months they got stronger they were able to lift more weights they were able to walk further and faster as a result of this muscle building it's kind of interesting because although muscle loss is driven by aging there's certainly a component of it which is driven by lack of activity yeah and it's kind of a psychological thing because as we get older we perceive ourselves as less able to exercise and obviously that's true you know don't go bonkers if you're in your 60s and suddenly start running out and you know pumping massive running marathons and pumping iron if that's not something you're used to but i think a lot of that decline is reversible.

58:10Dr Andrew Steele:So if you can start doing it, it's never too late, but it's also never too early. Great.

58:15Mike Milken:So Andrew, we've just upped the average age at the microphone here. I've returned and I have just a couple of closing questions, which of course is you. What is your most

58:25Dr Andrew Steele:important daily habit? I think my most important daily habit is actually building family and social connections. I've got a one-year-old baby at home and the evidence around this really shows us that people who maintain that social connection maintain that sense of community until later and later in life do tend to do better they tend to live longer they tend to live healthier but not only that you know i'm not seeing this baby thing as a purely reductionist way to expand my life expectancy i just think it's so important because you know what do we care about i think it's very easy you know we talk about lifespan we talk about life expectancy that's how long people live um there's a word that's really growing in popularity health span which is not just how long you live about how healthy you live how long you stay free from chronic disease how long you stay able to do you know the activities of daily living is the jargon but you know how long you're able to do your hobbies to travel to do the things you care about but i think the things that i really care about are the humans you know the people in my life it's my parents it's my friends it's my family and i think that's what makes life enjoyable and there's a bit of a movement actually you know we've done lifestyle we've done health span maybe we should start talking about joy span

59:26Mike Milken:and thinking how long we can stay happy for and finally there was an article in the times on November 28th on these two sisters who have been working on something called Link Jevity. Yes. I think it's Carina Lern and Serena Kern-Librera and they're up at Cambridge University and they're partly funded by Michael Hintze of, you know, CQS. You have been thinking about Think Tank. Just tell me a little bit about what are the next steps for Dr. Andrew Steele?

59:53Dr Andrew Steele:I've been thinking. I think the most important thing, my book came out in early 2021. I've been talking about this stuff to anybody who'll listen for the years that followed that. And I've really come to realise that the most important questions in this field, I'm fascinated by the science, I'm a scientist originally, but actually they're policy questions, they're finance questions, they're questions of getting policymakers and investors and members of the public interested in real longevity science. I think people, you know, some people read my book and they come away and they go, oh wow, you know, that's really cool Andrew, I'm going to start going to the gym or brushing my teeth more.

1:00:24Dr Andrew Steele:Those are important and worthwhile things and I don't want to denigrate public health at all. I think it's very, very, you know, it's critical and people can live longer and healthier lives as a result. But then I sometimes say to them, did you read the previous like eight chapters about medicines that literally slow down the aging process and might mean we have to worry slightly less about the lifestyle stuff, hopefully in the long run? And I think that particularly this word longevity, it's really come to mean a million different things to a million different people in the modern age. If you're scrolling down your social media feeds, you see, you know, people who used to be fitness influencers now talking about themselves as longevity influencers.

1:00:55Dr Andrew Steele:And there's a sense in which that's true. You know, I think exercise does literally slow down the aging process um looked at in the round and it's an incredibly effective form of medicine but i want there to be incredibly effective forms of actual medicine and i think that getting that message through to people is just so so important and the people i want to speak to about that are their politicians their policymakers their people who've got their hands on the lever of research funding they're also people who've got their hands on the levers of regulation because at the moment it's quite hard to get a drug approved for aging if you've got a drug that treats a specific disease then you know that's more straightforward you can often do the trial a bit more quickly because you can find a bunch of people with that disease and show that it improves their prognosis whereas if you need to do you know the first proposed trials on aging are probably going to be three to five years they're probably going to be 3 000 patients these are big phase three trials um and so maybe we need to have innovation prizes maybe we need to have accelerated approval pathways maybe we need to be thinking about integrating these uh trials into healthcare systems as they exist at the moment there are loads of big policy questions

1:01:49Mike Milken:the economic questions are vast so i'm not quite sure how how to even start my conclusion but i think that it is a subject that you um are deeply involved in and it deeply you know uh absorbs all of our you know not all of our time but a lot of our time particularly as we get older and you are pointing to some very significant steps that have been and are being made these uh you know these drugs around senescence and you know repairing the cell damage the importance of you know thinking about anti-obesity and i know in another talk you've you talked about you know why some of those compounds of the semaglutide for one being you know very you know beneficial that your point about dental health and inflammation is lost on a lot of people um and when we think about practically from an investment and keeping your finances in order i would remind everybody that savings are deferred consumption and we live in societies where debt where consumption is 65 to 70 % of GDP, and then I'm talking about those in the US and UK.

1:02:53Mike Milken:And so, you know, think twice before you spend randomly, twice I often give to my children. Eating less, there is definitely, you know, propensity gain in the West to eat more than, you know, is required. The reason that we own equities is that they're long duration assets. And as you think about your savings, the essential, you know, requirement to save, one needs to think about the components. And, a in a long-term asset portfolio but it isn't what generates those inflation you know beating returns and family and friendship is more important than fasting i would say so yeah and in terms of the

1:03:30Dr Andrew Steele:investing i think there's a fascinating case to be made here that investing in longevity science and longevity science company startups biotech it's a hedge because imagine this stuff works and you do suddenly find yourself staring down the barrel of 10 extra years of retirement if those companies are the reason that that's happened then you're going to have some money in order to fund those extra years of retirement. If the companies don't work, you're not going to live any longer and things come out in the wash. So I really feel like there's a case, perhaps on an individual level, but certainly for things like pension companies, if they can make some bets on these things, I think it'd be a fascinating financial hedge as well because the success of this is really the success of all of us in the long term.

1:04:04Mike Milken:So get your portfolio diversified. Andrew, it's been fantastic. Thank you for coming over to Germany. Maybe not exclusively for us, but we really welcome you here today and good luck with your great work.

1:04:14Dr Andrew Steele:Thank you very much indeed. Thanks for having me.