In this episode, we take a look at the science behind human aging and try to figure out what causes it, and what can be done to reverse it. We're joined by neuroscientist and neurophysiologist, Dr. James Lipton, to talk about what causes human aging, and how we can fix it. This episode is brought to you by Science Friday, a podcast produced by Popular Science and edited by Alex Blumberg. Copyright 2019 Science Friday. All rights reserved. This episode was produced by VaynerSpeakers. Used by permission. We do not own the rights to any of the music used in this episode. If you enjoyed this episode please leave us a five star rating and review on Apple Podcasts, and we'll read out your comments in future episodes. Thank you so much for any amount you can manage, and please remember to share it with a friend or family member who needs a good listening experience. It helps us to keep spreading the word about this important topic. Thanks to our sponsors, and all the support we can do our best to make a difference in the world. and we hope you enjoy this podcast and share it on your social media platforms! We look forward to hearing from you! Timestamps: 1:00:00 - What is the difference between a younger person and an older person? 4:30 - What does it mean to you? 7:00- What is aging? 8:20 - What causes it? 9: What is it like? 11:00 12: How fast? 14:30 15:15 - How fast is it better? 16: What can you do to get younger? 17: Is it faster? 18:40 - Does it matter? 19:00 | How fast can you become more resilient? 21:40 22:40 | What are you better than a better at something new? 26:20 27: What do you think you can do to improve your life? 29: Is there a better day? 30:30 | Is there more? 32:30? 35: What s faster than a young person better than an older? 36:00? 33:00 + 35:00 Is it better than you can grip something? 39:00 / 35:10 40:00 Can you be more agile?
00:01:08.000What's the latest in terms of what we understand in terms of what could possibly be fixed about human aging?
00:01:17.000Alright, so the fantastic answer to that question is there are no new revelations in terms of what we understand.
00:01:23.000Our understanding seems to have been pretty much complete already like 20 years ago.
00:01:28.000The fact that we haven't found out any fundamental new stuff that we didn't know before then is fantastic news because of course it means that we're unlikely to find anything out in the future either.
00:01:38.000It means that we are pretty much on top of the description of the problem and therefore it's all about solving the problem.
00:01:46.000Is it possible to summarize the problem?
00:01:51.000So aging is simply the same thing in a living organism like you or me as what it is in a car or an airplane or any other simple man-made machine.
00:02:00.000It's a fact of physics, nothing to do with biology, that any machine that has moving parts is going to do itself damage in the course of its normal operation as an intrinsic consequence of its normal operations.
00:02:19.000So in the same way that a car rusts or, you know, accumulates junk in the oil or whatever, similarly the human body does damage to itself.
00:02:27.000And again, just like a car or an airplane, The human body is set up to tolerate a certain amount of that damage so that we can get through to the point where we have kids before we start going functionally downhill, whether mentally or physically.
00:02:43.000But after that, evolution doesn't care about us anymore.
00:02:46.000And therefore we are only equipped to tolerate that much and eventually the damage that's being done accumulates to a point beyond what the body set up to tolerate and that's when things start to go wrong and we start to function less well.
00:03:01.000What is the difference physically between a younger person and older person in terms of their ability to recover from the damage of just regular everyday life and exercise and abuse and running around?
00:03:19.000So the difference ultimately arises from what the body is made of at the molecular level and cellular level.
00:03:26.000The body accumulates various changes that are chemical and biological consequences of what the body has to do to keep us alive from one day to the next, even starting before we're born.
00:03:37.000And those changes, the reason I'm using the word damage to describe those changes is because eventually things don't work so well.
00:03:45.000So you're quite right that recovery from injury is one thing that doesn't work so well, but so are plenty of other things.
00:03:52.000So whether it's how fast you can run, how fast you can think, you know, how strongly you can grip something, how fast you can walk, you know, all of these things become progressively less good.
00:04:03.000But the point is that the amount by which they become less good is pretty negligible until the age of 40 or 50. It's only then that the decline starts to accelerate.
00:04:14.000So what do you do in your own life to try to mitigate that acceleration?
00:04:19.000Yeah, I'm a really bad example of this.
00:04:29.000I'm just one of those hateful people who I can eat and drink exactly what I like and nothing seems to happen and I don't even need to exercise to speak of.
00:04:35.000And, you know, I'm biologically far younger than I actually am chronologically.
00:08:19.000Well, of course, it depends whether you drink too much.
00:08:21.000And too much is a different amount for different people.
00:08:24.000And so, you know, if you drink within your limits, you know, if you drink enough that you get a hangover in the morning, you know, once a week, then you're definitely drinking too much.
00:08:33.000The last time I had a hangover must have been when I was a teenager.
00:09:06.000That you push against the bottom of the river with.
00:09:09.000It sounds, when you describe it like that, like a really clunky activity, but actually it's fantastically smooth and when you get it, it's really easy.
00:09:18.000It's not even tiring and it's ridiculously romantic.
00:09:48.000What's a normal day for Aubrey de Grey?
00:09:51.000Well, there isn't really a normal day.
00:09:52.000I spend a ridiculous amount of time on the road because I view, you know, being a high-profile member of this community, I view the outreach side of things, just educating people on this as an enormously valuable and important part of my work.
00:10:05.000And also, it's something you can't delegate, because, you know, conference organizers or interviewers, for that matter, they always want the front man, whereas on the science side, we've been able to hire extremely good people, and so I've been able to delegate that to a very large extent.
00:10:19.000Now, in terms of progress, what has to happen for there to be a shift in the biological age of people where you could actually reverse it or where you could actually maintain the position they're at now for extended periods of time?
00:10:36.000First of all, let me answer that last part.
00:10:38.000So reversing aging is actually going to be pretty much the result of maintaining it.
00:10:45.000There won't be a just you maintain it because that would mean that you are repairing the damage of aging just exactly at the same speed that the damage is being laid down, which is ridiculous.
00:10:55.000You know, if you can do that, you can obviously do it a little bit faster than it's being laid down.
00:10:58.000So you don't really need to think about the maintaining part.
00:11:01.000However, what we need is we need to be able to repair all of the types of damage.
00:11:05.000And because the human body is so very complicated, there are, of course, a lot of different types of damage.
00:11:10.000So it's a divide-and-conquer strategy.
00:11:12.000Any of these types of damage at the molecular level, cellular level, can perfectly well kill you, more or less on schedule, however well we fix all the others.
00:11:20.000So since the beginning, Sensory Research Foundation, my organization, has focused on the most challenging, the most difficult types of damage.
00:11:30.000Because basically the easiest ones are being worked on by other people.
00:11:33.000We have, you see, we set ourselves up as an independent charity.
00:11:37.000So we're a charity, we're a public 501c3, which means that if someone gives us money they get a tax break.
00:11:43.000But we're independent, which means that we do not rely on peer-reviewed government grants or anything like that.
00:11:51.000The enormous advantage of that is that we're not competing with a lot of other people who have their own ideas about what to do.
00:11:59.000And in particular, the people who are deciding who wins that competition are not, you know, when you apply for government grants, it's terrible.
00:12:08.000You know, you end up having to basically emphasize really boring, low-hanging fruit just in order to have a chance at getting funded because people want to...
00:12:19.000Avoid funding things that don't lead to high-profile publications soon.
00:12:24.000So really ambitious, high-risk, high-reward stuff just doesn't get done.
00:12:28.000And so we focus on that because other people can't.
00:12:33.000And that's very unfortunate that that doesn't get done outside of what you're trying to do.
00:12:37.000Yeah, I mean, of course, this is a recognized problem.
00:12:40.000And the NIH, for example, have tried to address it with awards, with types of grants that are specifically focused on more cutting-edge visionary stuff.
00:12:54.000You know, it's less than 1% of the NIH budget.
00:12:57.000What's frustrating to you about the state of understanding repair and understanding the ability to fix things?
00:13:07.000Well, I'm not the kind of guy who gets frustrated very much.
00:13:11.000I'm always a glass half full kind of person.
00:13:14.000So for me, what matters the most is the fact that the understanding that this is what aging is and this is how to deal with it has improved so much over the years.
00:13:24.000So I started putting out the idea that this was the way to go after aging 20 years ago.
00:13:31.000Up until then, the only game in town, really, was we've got to make the body run more cleanly and generate this damage more slowly than it naturally does.
00:13:41.000And that's a very big conceptual difference, right?
00:13:44.000So it's not surprising that it took me maybe 10 years to really get the damage repair approach taken properly seriously by my colleagues in the scientific community.
00:13:54.000But by about 10 years ago, it was taken seriously.
00:13:57.000And in fact, over the past decade, people have been periodically reinventing the idea.
00:14:02.000And, you know, I don't necessarily always get as much of the credit as I probably ought to have, but I don't care about that.
00:14:06.000The main thing is I don't have to persuade anyone anymore.
00:14:09.000People get it that damage repair is at least, if not the way to go, at least a very promising way to go.
00:14:15.000So really what happens next is convincing people outside of the community, right?
00:14:21.000And there there's been enormous progress as well.
00:14:23.000So when you and I spoke last, five years ago, really that was the end of the story.
00:14:27.000I pretty much won the scientific argument, but still no one was really listening, right?
00:14:32.000And then over the past five years, the huge thing that's happened is the private sector interest in this has taken off.
00:14:40.000Typically, it's been led by the angel investor types, the seed investors, people who are willing to do really high-risk, high-reward stuff.
00:14:47.000But they understand that we're getting close enough that this is the next big thing, that we will actually have bona fide, genuine rejuvenation medicine in the foreseeable future.
00:15:02.000So, for example, the stem cell therapies now being used for aspects of aging with a really clear understanding of how they're going to work.
00:15:11.000Parkinson's disease is a great example of this, where stem cell therapy is the right way to go, and it's in clinical trials.
00:15:16.000Something that's been in the news a lot over the past couple of years is senolytics, which are drugs that selectively kill what are called senescent cells.
00:15:23.000So these are cells that hang out in the body in a bad state where they're doing more harm than good.
00:15:29.000Not only are they not doing what they're supposed to, they're also secreting nasty stuff that damages their neighborhood.
00:15:36.000And so drugs have been developed that are seemingly pretty good at getting rid of those, and they're in clinical trials as well.
00:15:45.000We basically do no work on that area anymore, hardly any.
00:15:48.000And we may end up doing none at all a couple of years from now just because other people are doing it.
00:15:53.000And so our money is better spent doing the stuff that's still at an earlier stage.
00:15:58.000And beyond that, you know, we are able, even for things that are a couple of years behind that, so won't be in clinical trials for another year or two, we've been able even then to get investors interested so that we can actually spin the project out as startup companies and focus on the things that remain.
00:16:17.000There's lots and lots of, I mean, literally way over 100 other companies now that I work with because they're not spin-outs from my foundation, but they are, you know, doing closely aligned work.
00:16:28.000And so I'm literally spending probably a day a week on average just making introductions between, you know, entrepreneur founders, scientific founders with great science and investors who want to get involved.
00:16:42.000The stem cell therapy is fascinating to me because I've had some personal experience with it.
00:16:46.000I've had some injuries that I cured with, well, doctors cured with stem cells in a remarkable way.
00:16:53.000We're at the point where I was told that I need shoulder surgery and I had a large rotator cuff tear and it's gone.
00:17:43.000So let me talk about the Parkinson's disease case in a bit more detail.
00:17:47.000So, what Parkinson's disease is driven by is the loss of a particular type of neuron.
00:17:52.000So, of course, in the brain, there's lots of different types of neuron.
00:17:55.000There's one type called a dopaminergic neuron, and they exist just in one specific very small part of the brain called the substantia nigra.
00:18:02.000So, it turns out those neurons, well, because they do a lot of work, basically, they die at a much more rapid rate than other types of neuron.
00:18:11.000So, we end up, all of this, with maybe...
00:18:14.000A quarter of those neurons that we had when we were young adults having gone by old age.
00:18:42.000If you think about it, what it is, basically you put cells into the body that have been programmed, have been developed into the right state in the lab, So that they know what to do when you inject them.
00:18:55.000They know, like, to divide and to then transform themselves to differentiate into the right kind of other cell.
00:19:03.000So what has been developed is dopaminergic precursor cells, stem cells that know how to become dopaminergic neurons.
00:19:09.000And those are injected into this one place, the substantia nigra, and they do that thing.
00:19:16.000So they're injected right into the brain?
00:20:27.000So a couple of years ago, there was actually a retrospective written by the group that did this clinical trial, and it was written specifically about the first responder, the first person who really got lucky and responded well.
00:20:37.000And it was written on the occasion of the 25th anniversary of that person being treated.
00:20:42.000What happened with that person was they were treated once, just got one injection, and the Parkinson's symptoms went away so well that the person was taken off their prior medication.
00:20:53.000There's this standard medication for Parkinson's called L-Dopa, which is a precursor molecule for dopamine.
00:21:10.000So, of course, now that we know so much about how to manipulate stem cells before we inject them, and therefore how to inject the right kind of stem cell, you know, people are very optimistic, and that's why there are clinical trials already ongoing right now.
00:21:23.000So what's really interesting to me is that during the time this person had this one injection, the rate of progress, the amount of understanding of how to manipulate these cells and make them exactly what you want has increased.
00:21:39.000And so what I was saying about how Sense Research Foundation is moving increasingly away from bothering work on senolytics because other people are doing it, That was already true when we started the foundation in respect of stem cells.
00:22:40.000So in order to answer that, I have to come back to what I said about this being a divide-and-conquer problem and the fact that we need to fix all of these things in order to really give the proper result in terms of biological age.
00:22:52.000Now, that means that any speculation that I may make about the timeframe for when we get there is a speculation about the most difficult parts of the problem.
00:23:02.000And therefore, it's highly speculative because the most difficult parts are at the earliest stage and therefore there's more opportunity for things to go wrong between now and then, so to speak.
00:23:12.000So when I am asked to give a timeframe estimate on this, I always make sure to emphasize that it's probabilistic.
00:23:19.000That what I'm giving you is a time frame for when I think we have a 50-50 chance of getting a decisive level of comprehensiveness of these therapies.
00:23:27.000And at the moment, that number is 17 years.
00:23:56.000The first piece of good news is that it hardly came down at all for the first 7 or 8 years.
00:24:02.000I would say, yeah, 5 years ago I was still saying 22, 21 years.
00:24:08.000So it hasn't been slipping any further for a little while.
00:24:14.000And the reason why things have speeded up to parity is because the only thing that was slowing it down before was lack of funding.
00:24:25.000Beforehand, I was always saying, this is how fast the science allows the problem to be solved.
00:24:33.000But the science only allows the problem to be solved if the science can be done and ultimately biomedical research is inherently expensive and we are just not able to pull in as much money as we need for this.
00:24:46.000That's interesting because it seems like that would be something that Most people would have a vested interest in funding.
00:25:09.000Just because it's so much easier to get people to write a cheque if they think there's a chance, even a really small chance, that they'll get their money back in spades sometime later.
00:25:21.000You know, I guess that's what you would expect.
00:25:24.000But yeah, I mean, of course, the other thing that we always are up against is the mindset that people have got into about aging, that they've needed to get into for all these millennia that we have been unable to do anything about it or have any prospect of doing anything about it anytime soon.
00:26:10.000You know, and thereby pretending, for example, that it's not really like a medical problem at all, you know, and that it's like inevitable and universal and natural, or alternatively saying, well, okay, maybe we could fix it if we tried to, but it would be a bad thing, that aging is some kind of blessing in disguise.
00:26:28.000Yeah, and that's where all this stuff comes from about, oh dear, where will we put all the people or how will we pay the pensions or won't dictate us forever or won't it be boring, you know, which I have to spend my whole life contending with.
00:26:38.000How do you get over the dictators living for everyone?
00:26:41.000Well, you know, last time I looked, dictator was fairly high on the league table of risky jobs.
00:26:47.000You know, I mean, not a lot of dictators die of aging in the first place.
00:26:50.000And furthermore, the ones that do die of aging, they tend to have organized their succession in advance anyway, so it's as if they were already immortal.
00:26:56.000Well, not only the percentage of dictators versus the percentage of regular people is so incredibly small to not cure aging because of dictators seems like the dumbest idea ever.
00:27:08.000I mean, but people really, you know, this is what people do, right?
00:27:12.000They will come up with some reason why aging is a blessing in disguise.
00:27:16.000And then they will instantly switch off their brains for fear of actually coming up with a refutation of that reason or even listening to it.
00:27:22.000The romantic aspects of aging are the weird ones, right?
00:27:59.000I tend to feel that there's a problem with calling aging a disease, which is that it makes it sound like it's something that could be cured with a one-off therapy, like, you know, an infection.
00:28:15.000And as such, it's something that you can repair, you can stave off, but you have to do it periodically because the damage is going to continue to be created.
00:28:26.000And the reason why that's important is that it determines what kind of What kind of medicine we look for.
00:28:36.000A lot of Alzheimer's research, for example, in fact, I would say most of Alzheimer's research has been predicated on this kind of mistake, on the idea that if we can just cure Alzheimer's, then, you know, so I would say that actually, it's not that the word disease is used too narrowly.
00:28:53.000And should be broadened to include aging.
00:28:56.000Rather it's the other way around, that the word disease is used too broadly and should be narrowed so as not to include things like Alzheimer's that are actually parts of aging.
00:29:07.000Because really the difference between the progressive chronic conditions like Alzheimer's that we call diseases and the ones that we don't, like, you know, loss of muscle or declining the immune system or whatever, You know, the only difference is semantic.
00:29:20.000Some of them, you know, they're both parts of aging.
00:29:22.000Some of them are ones that we've chosen to give disease-like names to.
00:29:26.000What would you call aging if you don't call it a disease?
00:29:52.000So as I said, because this is a divide-and-conquer problem with a bunch of different types of damage, all of which we need to fix, then we need to look at what fixes are available for each individual type.
00:30:04.000So what stem cells are there to fix is cell loss.
00:30:08.000Where cells are dying and they're not being automatically replaced in the body by cell division.
00:30:13.000Have you personally experienced any stem cell therapy?
00:30:24.000You know, of course, the nature of aging is that because it's progressive and because it only causes functional decline after a certain point, there's a tradeoff that one always has to keep in mind in terms of timing of a therapy between how badly one needs it and how rapidly the quality of the therapy is improving.
00:30:42.000So, you know, if I take a stem cell therapy now...
00:31:21.000So, yes, in terms of other things, so senolytics do not compete with stem cells because senolytics are there to do a different thing, to fix a different type of damage, namely the accumulation of these bad cells.
00:31:32.000And then you've got to have cancer therapies.
00:31:34.000You've got to have therapies that remove molecular waste products from inside cells.
00:31:38.000A couple of our start-up companies are doing that.
00:31:42.000You've got to remove waste products from outside the cells, for example.
00:31:45.000So people have used the immune system to do that.
00:31:48.000You've got to repair DNA in the mitochondria, these special parts of the cell that do the chemistry of breathing.
00:31:55.000You know, there's a bunch of different things we have to do.
00:31:59.000Another piece of good news, I told you earlier on that there's been no real change over the past 20 years in our understanding of what the problem is.
00:32:07.000There's also been no real need to change our preferred approaches to each of the damage repair technologies.
00:32:15.000We haven't found bad news that says, oh dear, this potential approach to fixing this particular type of damage isn't going to work for this new reason that we didn't know before.
00:32:25.000Therefore, we have to start again and think of a new one that hasn't happened either.
00:33:03.000I mean, some people view it as an intellectual pursuit, but I don't.
00:33:06.000I really feel, you know, ever since I was a young kid, I have wanted to spend my life making a difference to the world, improving the quality and, of course, in this case, quantity of life of humanity.
00:33:19.000I'm just one of those incredibly lucky people.
00:33:21.000I've been able to end up in this position of essentially leading the crusade to do that in the biggest possible way.
00:33:28.000So this is something that you felt compelled to do from a really early age?
00:33:33.000So what actually happened was that as a teenager, having pretty much decided that this is what I wanted to do with my life, the first thing I did was I got into artificial intelligence research.
00:33:43.000And the reason that happened was because when I was a teenager, I tried my hand at programming.
00:33:48.000And I thought, well, okay, one of the big problems in the world is the problem of work.
00:33:53.000The fact that people have to spend so much of their time doing stuff that they would not do unless they were being paid for it.
00:33:58.000And therefore, we need more automation.
00:33:59.000So I'll work on that because I'm good at it.
00:34:02.000And I had no reason at that time to believe that I was going to be any good at biology, but specifically, particularly.
00:34:07.000And there were other people who were particularly good at biology, and I had made the mistaken but absolute assumption that everybody realized that aging was by far the world's biggest problem, and therefore biologists would be working on it and grinding away.
00:34:21.000And of course you didn't hear much, but hey, it's a really hard problem, so that's not a surprise.
00:34:25.000So it wasn't until my late 20s that I found out that I was wrong.
00:34:28.000What happened was that I met and married a biologist.
00:34:32.000Quite a senior one, actually, who was a full professor at that time at UC San Diego.
00:34:39.000And through her, I not only learned a lot of biology just by accident, you know, over the dinner table, but I also found out, gradually, that she wasn't interested in aging.
00:34:49.000I just kind of, it hadn't occurred to me, so it didn't come up in conversation.
00:34:52.000I began to notice that it wasn't coming up in conversation.
00:34:56.000I started asking questions, and she would say things like, you know, well, I mean, like, it's just decay, isn't it?
00:35:01.000And I would say, well, yeah, but so what?
00:35:04.000And she said, well, I mean, you're not going to learn any fundamental truths about the universe from studying decay.
00:35:10.000And I would say, well, that's true, yes, but it's bad for you.
00:35:14.000And she would say, but that's not my problem.
00:35:40.000And I happened to have inveigled myself into a position where switching fields was something I was able to do.
00:35:47.000I had a very undemanding job at the University of Cambridge doing bioinformatics, which allowed me to do my artificial intelligence research in my spare time.
00:35:58.000I was being paid well enough, and I had access to university facilities and all that.
00:36:03.000So all I needed to do was repurpose my spare time and, you know, start paying my way to go to conferences because, of course, back then nobody knew me and I wasn't being invited.
00:36:14.000I started doing quite well-received stuff.
00:36:16.000And so I became quite well-respected in the field very quickly.
00:36:21.000And for the first five years that was all that was happening because I was basically harmless and it was then five years in, in the year 2000, that I had this kind of eureka moment that damage repair was the way to go and started talking about what the impact could be and people started to think I had gone completely crazy and it took a little while for people to come around.
00:36:41.000So when you say that at an early age you felt compelled to try to help people, what was that?
00:36:49.000It was all down to my mother's desire for me to practice the piano.
00:36:57.000She wasn't a particularly good pianist herself, but she wanted me to learn how to play piano, and so she put pressure on me to practice all the time, and I was resistant.
00:37:05.000But somehow or other, My mother had already instilled in me a sense of introspection, you know, a desire to understand why I thought what I thought.
00:37:15.000So I actually decided to think about why I didn't want to play the piano.
00:37:20.000And it took very little time for me to realize that the fundamental reason I didn't want to spend so much time tapping away on this thing was that the best case outcome of this would be that I would become a good pianist And that was just not good enough.
00:37:36.000You know, because there were already lots of other good pianists.
00:37:40.000So I would not be, you know, contributing significantly to the quality of life of mankind by becoming just another one.
00:37:56.000So over the next few years, I'm going to say, this general idea that playing the piano was a waste of time crystallized into the understanding that I could actually articulate that I wanted to make a difference to the world.
00:38:10.000And so that's how I, you know, by the time I was 15 was when I started programming and I've just told you the rest.
00:38:17.000That's an interesting mapping out of your future.
00:38:19.000You know, at nine years old, recognizing you're not going to make a significant contribution to the world by doing something that other people have already done.
00:38:32.000I can't imagine her thinking like that.
00:38:36.000I mean, when I started working, actually, at this bioinformatics project that I mentioned, I had a lot of exposure to a lot of Top flight biologists.
00:38:48.000And it turns out that there were fields that were just fashionable, right?
00:38:54.000And lots of top biologists would be competing vociferously with each other to make the next advance in one particular narrow area that was just really fashionable.
00:39:04.000And other areas would be just completely neglected.
00:39:10.000Why are these smart people choosing to do something that minimizes the likelihood that they will have any impact?
00:39:18.000In other words, basically, whatever they find out, they themselves didn't matter at all because they could have been hit by a truck or done something completely different and someone else would have found out the exact same thing ten minutes later.
00:39:56.000But no, I think the one thing to make a difference is just intrinsic in me, and it's just something that I just realized as a result of the introspection.
00:40:07.000When you look back at that now, that's got to be an interesting course where you've recognized at a very young age that you wanted to make some sort of a difference.
00:40:16.000But knowing that you had had that epiphany at a young age when it comes to being a pianist or doing something that's going to significantly impact people that is not a standard path that many people are going on.
00:40:30.000It's a very interesting way to set up your life.
00:40:36.000Well, I wouldn't say I set my life up.
00:40:39.000I'd say I had intentions, but if we look at how I got from there to here, an enormous, enormous amount of it was just sheer luck.
00:41:46.000Is there anything that frustrates you about this pursuit?
00:41:50.000I'm not an easily frustrated kind of guy.
00:41:53.000I mean, of course, sometimes it gets to me how slowly things are going, how resistant people are, how irrational the resistance is.
00:42:02.000But even there, you know, I've already, from some of the things I've already said, you understand that I'm really...
00:42:09.000Sympathetic to humanity in this regard.
00:42:11.000I understand that most people just, you know, the psychological burden of the prospect of physiological decline is so enormous that they've got no choice.
00:42:24.000They've got to put it out of their minds.
00:42:26.000And, you know, some people feel, I don't know, psychologically stronger or whatever, and they can bite the bullet and actually work on this, even though it's a very, very long haul.
00:42:37.000But some people aren't, and that doesn't mean that they are less deserving of the benefits.
00:42:43.000It's a very strange thing where people put on intellectual blinders and they're talking about aging and dying.
00:43:46.000Was that the hypnotist says, okay, this is actually your right elbow and this is your left elbow.
00:43:50.000So he switched the guy's elbows, right?
00:43:52.000No elaboration of the implications of this, just saying, just getting the person to completely, completely implicitly believe this thing, right?
00:44:01.000And then he said, right, I would like you please to touch your right elbow with your left forefinger.
00:44:08.000And so, of course, there was all this wriggling and writhing and so on.
00:44:32.000Ask the guy to explain why he couldn't do it.
00:44:35.000And here is the coup de grace, because what happens is the guy gives a completely unhesitating, lucid, grammatically correct explanation for why he couldn't do it.
00:44:45.000And the explanation, of course, will have a hole in it the size of Canada, but the fact is, the guy won't see it.
00:45:12.000So when I started to have these discussions with people about aging and started to find out that people make these unbelievable arguments in favor of it...
00:45:24.000You know, I call it the pro-aging trance, and it was based on that experience from my youth.
00:45:30.000Yeah, I've always said to people, if there was a pill that you can take that would stop all aging, all deterioration, and all diseases, You'd be a fool not to take it.
00:45:48.000If it was a rare thing that people aged, a very rare thing, we would look at it with great sadness.
00:45:54.000If someone was afflicted with this aging, we saw someone...
00:45:58.000Hunched over with severe arthritis and osteoporosis and deterioration of the joints and decaying of the cognitive function and they don't know where they are, who they are, we'd be so sad.
00:46:52.000Well, of course, a large part of the reason why it's difficult to get the real answers across is because so much fiction, science fiction, has been written, and of course movies, giving wrong answers and making a dramatic element out of it,
00:47:07.000whether it's Blade Runner or In Time or any of these movies.
00:47:23.000The real answer is very straightforward.
00:47:24.000It's simply that other technologies that are coming along already and will be established, well established and ubiquitous before we get this to happen, are going to solve the problem because they will increase the carrying capacity of the planet.
00:47:40.000Remember that the reason why we have too many people today and we've got environmental consequences is not because of lack of space.
00:47:48.000It's because of the amount of pollution that the average person generates.
00:47:51.000Specifically, of course, the biggest thing being pumping carbon into the atmosphere.
00:47:57.000But, of course, whether it's plastics or whatever.
00:48:02.000You know, we've got solar energy and wind energy now that are completely exploding and they're going to completely replace fossil fuels.
00:48:11.000And we got there without people even having to wake up and realize that climate change is actually quite an urgent problem.
00:48:18.000We got there simply because the technology got to be good enough that the production of a kilowatt hour of energy is actually cheaper with the renewable energy mechanisms than it is from fossil fuel.
00:48:31.000So artificial meat, you know, within not very long is going to be both tastier and far cheaper than regular meat.
00:48:38.000And the amount of space we're going to save, let alone the amount of methane that we're not going to be generating, is going to, you know...
00:48:45.000I haven't heard anything saying it's going to be tastier.
00:49:10.000And so there is no way that one can make a realistic, plausible argument that denies that the carrying capacity of the planet will rise far faster than the population.
00:49:25.000We don't even need to take into account other things like the fact that fertility rates are coming down everywhere and that once you can live a very long time, they're probably going to come down even further because people who are now choosing to delay having their kids by five years will be able to delay having them by 50 years.
00:49:47.000Do you have that same optimistic perception about the ocean?
00:49:50.000Well, first of all, let me say what I think about the word optimism.
00:49:55.000Because I know that you're not doing this, but a lot of people, when they talk to me and call me an optimist, they actually mean that I'm an over-optimist.
00:50:04.000And when they call themselves a realist, they mean that they're a pessimist.
00:50:08.000But anyway, about the ocean, of course.
00:50:12.000You know, certainly there's a lot to do.
00:50:15.000One big problem right now, of course, is the ocean is storing a lot of carbon and releasing a lot as it's warming up.
00:50:21.000So we definitely have to fix that as well, but it's part of the same problem.
00:50:24.000You know, the less carbon there is in the atmosphere, the less of a problem that is.
00:50:28.000Direct carbon removal from the atmosphere is a technology that's absolutely burgeoning now, and direct carbon capture from the ocean seems to be something that's equally plausible, though it's obviously different.
00:50:44.000I'm optimistic in terms of the ability to clean up the ocean.
00:51:01.000The depletion of the fish populations is at an unprecedented rate, and it seems to be we're somewhere in the neighborhood of 50 years away from a catastrophic, complete collapse of wild fisheries.
00:51:38.000I mean, most of, as I understand it anyway, this is not an area I'm expert on, of course, so I may be wrong, but… Most of the severe depletions of populations of specific fish species are because of fishing, because of overfishing.
00:51:54.000So if we're not doing the overfishing because we're making the same fish elsewhere on land, Well, I'm sure a lot of it is being done by the United States and Great Britain and a lot of first world countries, but I'm sure a lot of it is also being done by countries that can't afford to make this artificial fish or don't have the access to it,
00:52:13.000or at least in the time period that it's going to take before these fisheries rebound.
00:52:19.000When I talk to people that have an understanding of wildlife in the ocean, they say it's a desperate time.
00:52:24.000And it's a desperate time that is not really being recognized by the general population because they can still get sushi, they can still get halibut at the local market.
00:52:33.000But if you talk to the fishermen, if you talk to the wildlife biologists that are really studying the levels, they're like, this is nearing a point of no return.
00:53:21.000I'm really optimistic about artificial meat.
00:53:24.000I mean, it seems that at one point in time it was like a quarter million dollars for a hamburger, and now they've got it down to a point where you can actually make an animal meat product that does not come from an animal dying.
00:53:48.000And I'm excited about what you're saying that I think people think about overpopulation.
00:53:54.000One of the things that you should take into consideration is that as populations increase in places urbanized, the actual birth rate goes down to the point where places like Japan, there's actually a concern that they're not having enough children.
00:54:09.000And of course, it is driven by prosperity, you know, female education and emancipation and so on.
00:54:14.000So at this point, if you look at the largest countries in the world, the largest dozen countries in the world, the only one that has a really high fertility rate still is Nigeria.
00:54:25.000You know, if you exclude sub-Saharan Africa, it's basically a completely solved problem.
00:54:33.000Yeah, if you look at the big countries you would not expect, like Bangladesh or Pakistan or India, you know, their fertility rate is down below three now.
00:54:49.000People often used to say that the only reason why China's fertility rate is low is because of the one-child policy, which of course they have now discontinued precisely because of problems like this.
00:55:39.000So, you know, a huge amount of the so-called debate that goes on about the desirability of all of this just goes away when you remember that people actually quite like being healthy.
00:55:49.000But in terms of how the world will be, which is a question you asked, there's two questions here.
00:55:54.000One question is how will the world actually be, and the second question is how will people in the near term expect the world to be?
00:56:01.000And the reason why those two questions are important to distinguish is because the question of how the world will actually be is very obviously completely unanswerable, even if we look 50 years in the future.
00:56:13.000I mean, if you look 50 years ago, right, how much of what we have today would have been predicted, right?
00:56:48.000There's going to become a point where people in general, the general man in the street, starts to realize that they're probably going to live an awfully long time because they're not going to just get progressively thicker as they get older.
00:57:05.000And, you know, lots of other reasons are going to exist why they're going to live a long time, like we're going to have self-driving cars that pretty much eliminate, you know, road accidents and so on.
00:57:14.000So, they're going to want a lot of different things than what they wanted when they thought they were going to live only slightly longer than their parents.
00:57:24.000They're going to want very different pension plans, very different life insurance, health insurance, very different inheritance arrangements.
00:57:31.000And these are huge, big ticket items, right?
00:57:34.000They basically drive the global economy.
00:57:37.000So policy makers and decision makers around the world had damn well better be ready for that shift in public expectation of how long they're going to live.
00:57:49.000Now, therefore, it is absolutely critical to estimate and to communicate the estimate of how soon that shift in public expectation is going to occur,
00:58:05.000which means what events have to happen, how much progress needs to happen in order to cause that shift.
00:58:15.000Now, this is where I am terrified of Because I think it's going to happen really soon.
00:58:22.000I think it could easily happen in the next three to five years, and that when it does happen, it's going to happen incredibly suddenly.
00:58:32.000Here's the sequence of events that I think is going to happen.
00:58:35.000Step one, we're going to have sufficient progress in the laboratory or the clinic that most of my scientific colleagues are going to be willing to come out and say, more or less,
00:58:51.000yeah, Aubrey de Grey was right all along.
00:59:15.000Here's what I think is going to happen, but I want to know whether you think I'm right.
00:59:18.000I think the next thing that's going to happen is that real opinion formers, people like you, people like Oprah Winfrey, are going to hear that being said.
00:59:29.000And they're going to say, oh shit, this is actually going to happen.
00:59:37.000And they're going not only to say what their opinion is, but they're going to say what they think people ought to do.
00:59:43.000In particular, they're going to say, well, look, you know, let's actually, if it's only a matter of time, if we're losing 110,000 people every day worldwide to this phenomenon, then we do kind of have a bit of a moral obligation to make it less time if we can.
01:00:00.000So my sense is that once that happens, the following day, it's going to become impossible to get elected unless you have a manifesto commitment to, you know, have a war on aging, you know, throw proper money at this.
01:00:12.000I mean, I really mean a proper war on aging, not just like the war on cancer was.
01:00:17.000Not just to do the research, but also to front load all of the investment in infrastructure and, you know, training of medical personnel and so on.
01:00:28.000Like, the public is going to make that switch I just mentioned of expectation, like, at once.
01:00:33.000So it's going to be ridiculously sudden once it happens.
01:00:37.000And the first step is going to be that shift in what my colleagues in the biogerontology community feel able to say on camera and on stage.
01:00:50.000Now, therefore, the question is, what amount of progress is going to be required for that to occur?
01:01:30.000The fact that unlike me, those people are reliant for most of the money that drives their research on peer-reviewed government money, government grants.
01:01:45.000And they just won't get them if it's possible to accuse them of saying irresponsible things to the media, things that get people's hopes up unduly.
01:01:58.000Remember, there's nowhere near enough money.
01:02:01.000There's less than 10% of the necessary money to fund research at the moment.
01:02:05.000So the committees that decide who gets money and who doesn't are always desperately scouting around for reasons to say no that can be justified.
01:02:15.000And saying, oh, this guy says irresponsible things to the media is a totally safe way to say no, right?
01:02:29.000David is probably the person out of my colleagues who pushes the envelope as much as possible out of people who have regular faculty positions.
01:02:38.000But, you know, he's just written a book, which I see you have on your shelf, called, you know, Why We Age and Why We Don't Have To.
01:02:45.000He could not have written that book with that title five years ago and kept his job.
01:03:00.000There's a tension here between, on the one hand, not saying things that can be characterized as irresponsible, but on the other hand, not saying things that can be characterized as simply untrue.
01:03:11.000So the more progress is made in the laboratory, not even in the clinic, just with mice, in terms of actually rejuvenating them, making them live longer with treatments that were given to those mice when they were already in middle age.
01:03:25.000The more progress is made, you know, the more impossible it's going to be to carry on being pessimistic and refusing to make time frame predictions or anything like that.
01:03:36.000So there's almost a forced pessimism that's created by the establishment.
01:03:40.000Well, I think what you're saying makes a ton of sense in that once it does get to the point where this is undeniable, this is peer-reviewed, proven, established science, and also implementable, this is something that can be...
01:03:57.000At scale, distributed worldwide, yeah, things are going to get real weird.
01:04:01.000So people are already – people are obviously still going to be saying it can't be done in humans, you know, it can't really be done, you know, until the cows come home, you know, just in the same way as has happened for any other pioneering technology throughout history.
01:04:17.000But what matters is what the center of gravity of expertly – stated expert opinion is.
01:04:24.000It is a really, really polarizing subject.
01:04:28.000I mean, it is funny how what you're saying rings so true that academics and intellectuals have to be cautious about talking about even what is potentially possible, even though in private they probably are more than aware that there's just a few steps to go before this stuff gets implemented and we see really I mean,
01:04:54.000Yeah, and I mean, I'm not saying that all of us absolutely agree on 100% on everything in the science.
01:04:59.000Certainly, I would say that I'm slightly on the optimistic end of the spectrum of expert opinion.
01:05:05.000But yeah, my colleagues are not all that far behind me in terms of what they would say the timeframes are.
01:05:10.000What you're saying in terms of people discussing it in the media makes absolute sense to me.
01:05:14.000That as soon as that Pandora's box gets opened, then people are going to be looking to establish clinics everywhere, and it could be very strange.
01:05:24.000Well, even if a lot of these things are not yet available for clinical use, even if some of them are still...
01:05:31.000At the beginning of the clinical trial process, and we're still maybe 10 or 15 years away from the real Mackay, you know, that will still be enough to trigger this pandemonium.
01:05:40.000And that's why policymakers, decision makers in every way, both in government and in key aspect of industry, need to, I call it, anticipate the anticipation.
01:05:54.000Thought through and prepared for this change in public expectation of how long they're going to live.
01:06:00.000So you think that this One day will be a gigantic public issue in terms of elected representatives that they're going to need to have some sort of an anti-aging policy.
01:06:22.000And do you think one of the motivating factors would be the price of healthcare, that the argument would be part of our issue with healthcare and the An incredible amount of money that needs to be spent on hospitalizing people and treating them with diseases.
01:07:34.000In the US and the UK and everywhere else, the overwhelming majority of medical expenditure is on the health problems of the elderly, which will go away.
01:07:43.000Now, of course, the medicine that makes those problems go away is not going to be free, I mean, to produce and to deliver, but prevention is always better than cure.
01:07:54.000But that, actually, is only a minority of the economic benefit.
01:07:58.000The real economic benefit comes from the indirect costs.
01:08:02.000First of all, the fact that the kids of the elderly are going to be more productive because they're not having to spend time looking after their sick parents.
01:08:22.000Anything to do with the retirement age.
01:08:24.000This comes back to another aspect of the interaction between emerging technologies.
01:08:29.000So, of course, we've got automation coming.
01:08:31.000I don't work on it anymore, but lots of people do, right?
01:08:33.000We're making huge progress in artificial intelligence and most people, even conservative commentators, say that most of the jobs that exist today are going to be gone 20 years from now.
01:08:45.000Because machines will be doing things perfectly well.
01:08:47.000So, you know, we're going to be completely unable to continue this system of an economy based on full employment.
01:08:55.000You know, last time this happened with the Industrial Revolution, we got away with it by inventing an entire new sector.
01:09:01.000You know, the service sector that replaced all the jobs that people didn't have anymore in manufacturing and agriculture.
01:09:06.000You know, it's not going to happen this time.
01:09:25.000But, you know, that kind of thing is going to happen.
01:09:29.000I can totally imagine a situation in which, you know, 30, 40 years from now, work is something like national service used to be.
01:09:40.000When you're young and insignificant, you do a few years of actual work and then you...
01:09:50.000Yeah, but that means that the whole concept of pensions, it's ridiculous to think about that.
01:09:53.000So we've got to get policymakers out of that mindset and to get them to think in more global terms about the health benefits and the benefits to quality of life of everybody and so on.
01:10:03.000It is funny that work or the concept of work is sort of inexorably connected to society to the point where you think you have to work.
01:10:11.000But, you know, meanwhile, people lived for hundreds of thousands of years without even the concept of that, you know, like a place where you go where they give you gold coins.
01:10:22.000I mean, of course, you do have to have something that makes something that fulfills something to do that you find fulfilling.
01:10:29.000That's the argument for universal basic income, right?
01:10:32.000The argument against it is human nature, that people need to be motivated and they need something to sort of guide them towards excellence.
01:10:40.000Yeah, my take is the only thing that needs is better education, which of course is something that we could spend the money on that we save from not having to...
01:11:36.000It's based on aggregating a whole bunch of different areas of research.
01:11:42.000But, of course, I'm fairly well informed about where research currently is and how rapidly it's moving in a variety of different areas.
01:11:48.000And so just, you know, I'm putting all that together in my head and I'm saying, how soon are we going to be able to take mice that normally live, let's say, two and a half years and do nothing whatsoever to them until they are one and a half and get them to, on average, live to four instead of two and a half,
01:12:37.000I mean, a lot of things have extended lifespan a fair bit.
01:12:43.000But what we have at the moment is not all the components of what I just said.
01:12:49.000If you do something genetic to mice, or if you do it to them throughout their lives, then we can already get that year, year and a half out of mice.
01:13:08.000You've got to be able to start late and get the big extension.
01:13:11.000And you're not going to get that without bona fide rejuvenation.
01:13:15.000So that's not going to come by way of genetics?
01:13:17.000Well, even if it did come by way of genetics, it wouldn't matter.
01:13:21.000It wouldn't persuade my colleague or me that we were on the brink of doing it for humans who have the misfortune of being already alive.
01:13:29.000So the rejuvenation is going to come through some sort of biologics?
01:13:34.000Well, yes, through the kinds of things we're working on that I mentioned earlier.
01:13:37.000Stem cells, gene therapy to do various things to introduce, for example, bacterial enzymes that can break down waste products, senolytics that I talked about, pharmaceuticals to do other things.
01:13:58.000So CRISPR is a technology that was first developed about eight years ago now and it is the exploitation of a bacterial mechanism that allows bacteria to defend themselves against viruses.
01:14:12.000Essentially how it works is that it allows us to change the sequence of our genome in a particular cell in a very specific way.
01:14:26.000And there are other technologies for gene editing that already existed before CRISPR that are very laborious, very expensive and very clunky that is far, far cheaper and easier to use.
01:14:37.000So what that does is it allows us, for example, to inactivate a gene, or for that matter to change the sequence of a gene from a mutant form into a normal form so that it works when it was previously not working.
01:14:52.000Now, doing that in the laboratory in a Petri dish is fair enough.
01:14:57.000The question is, can we do it in the body?
01:15:02.000Initially, this technology was too error-prone.
01:15:05.000It was prone to do what George Church has called genetic vandalism and have what's called off-target effects.
01:15:15.000In other words, basically do other changes to the genome elsewhere that you didn't want.
01:15:20.000But, of course, people have known this, and people have been working really hard to improve the technology, and it's getting to the point now where it's possible to actually use it on humans, maybe.
01:15:34.000Now, you can't do everything with CRISPR. One thing you definitely can't do with CRISPR is insert new genes into the genome, and that's something we really need to be able to do.
01:15:44.000But actually, one of our big projects is a kind of two-step thing where we use CRISPR to make a small change to the genome that allows us to insert large genes where we couldn't previously.
01:16:10.000What happened was that a group in China used CRISPR to alter the DNA of embryos that were going to be used for IVF, for embryo fertilization.
01:16:22.000And the change that was made was itself quite a curious one.
01:16:28.000Essentially what they did was they tried to change a gene called CCR5 into a mutant form that doesn't work, but that in its inactive form protects the body from infection by HIV. This is something that was discovered a long time ago,
01:16:46.000and maybe 1% of people have this genotype, and so this was introduced.
01:16:54.000Unfortunately, first of all, it probably wasn't done very well, but also...
01:16:58.000Well, people have looked at the process, and they probably didn't make the correct modification.
01:17:08.000But also, it's not clear whether doing it for someone lifelong is actually a good thing because, as I say, it's an inactivation of a gene that must exist for a reason or it wouldn't exist at all, right?
01:17:35.000But yeah, so anyway, the other thing was that it's not obvious why it's even worthwhile to make An embryo genetically resistant to HIV. First of all, they don't have HIV yet in the first place, and they may never get it.
01:17:49.000And secondly, we've got drugs that work pretty well to control HIV, antiretrovirals.
01:18:03.000Well, when I hear about something like that, I always assume, first of all, I mean, this American prejudice, you assume that it's in China, they're doing something crazy, right?
01:18:11.000And you also assume that if they're telling you about someone who's been altered, that means that they've probably been doing this for a decade.
01:18:20.000Or since CRISPR was initiated eight years ago.
01:18:40.000That these are not adequately regulated treatments, and they are certainly not adequately characterized.
01:18:50.000In other words, the people who get the treatments are people who pay for them rather than people who have been chosen to be in a standardized group of any kind, and there tends to be very little follow-up.
01:18:59.000But still, it's better than nothing in the sense that some information exists about the efficacy and safety of these treatments as a result.
01:19:10.000The more that people who are administering these treatments can be induced to reveal their data, the better, even if it's anonymized.
01:19:20.000But, you know, some scientists, quite a lot of scientists...
01:19:25.000Take a much stronger view that, you know, we just should oppose all of this, period.
01:19:30.000And we should just say, you know, everyone who indulges, who gives treatments to people in offshore places should be shut down as best as we can and should be demonized.
01:19:45.000Personally, I've had my family, my mother has gone to Panama twice and she was on the verge of a knee replacement and now she walks without pain.
01:19:55.000Yeah, I bet she went to Neil Reardon's clinic.
01:19:58.000Yeah, I mean there are a lot of people who have very good stories out of Neil's group.
01:20:05.000Of course, the thing is, you don't know, unless someone has a really bad story, whether things are going wrong.
01:20:12.000So, I mean, I don't know whether Neil releases the total number of patients per year that he treats.
01:20:22.000I just do know that I have spoken to several fighters from the UFC that have gone down there.
01:20:29.000And again, my mother was, I mean, she didn't want to get a knee replacement.
01:20:32.000So when I sent her down there, and it took, because she's, I'm 52, she's 73. So it took her somewhere around six to eight months before she started feeling anything.
01:20:45.000She was really worried that it wasn't going to work.
01:20:47.000But then at eight months in, the pain just went away, and it's continued to get better, and then I sent her down a second time, and I'm going to keep sending her down there.
01:20:56.000What's fascinating to me is they do three days of intravenous therapy, and the intravenous therapy has, I don't know if it's just my imagination, but she looks younger.
01:22:13.000But it does mean that we're on a learning curve and it's vital to have the people like Neil, who are administering this therapy to quite a lot of people, to actually not just, you know, live off the stories of high profile people who get good benefits and talk them up.
01:22:45.000So many therapies in regenerative medicine in general have the potential to be beneficial over the first few months to a year or whatever and then to start having side effects that are detrimental.
01:22:58.000What have you heard that are detrimental side effects?
01:23:01.000So, well, of course, the biggest thing that we always have to worry about is cancer.
01:23:06.000Because, and this is true for a whole bunch of things, you know, telomerase activators and so on.
01:23:12.000The thing is that aging can in some senses be characterized as a trade-off between cancer and everything else.
01:23:20.000In other words, a huge amount of what...
01:23:24.000What goes wrong with the body late in life is as a result of a kind of dialing down of regenerative functions that we actually do naturally have in the body, but which are not as active in older people as they are in younger people.
01:23:40.000And so, of course, we have to ask, why are they less active?
01:23:43.000And a lot of biologists, including myself, believe that a huge part of that is adaptive.
01:23:49.000In other words, it is Kind of the body recognizing that there is, as time goes on, a progressively higher number of cells in the body that are almost cancerous and that have to be kind of kept in check in order not to become properly cancerous.
01:24:05.000Because, of course, cancer is the result of a gradual accumulation of mutations and so on in the cells, right?
01:24:11.000And so yes, every time that you are improving regenerative capacity, whether of the cells that you put in or more importantly of the cells that are nearby the cells you put in, you are potentially taking a risk of hastening the onset of actual cancer.
01:24:31.000What is your opinion on the benefits of fasting in that regard?
01:24:38.000First of all, we'll talk about fasting in relation to cancer because that's important.
01:24:41.000People have certainly found that it's a good thing to do, which is somewhat counterintuitive because in the later stages of cancer, there's, of course, cacaxia, you know, a lot of loss of muscle and so on.
01:24:54.000But earlier on, it seems that we can slow things down.
01:24:57.000I mean, cancers are greedy metabolically.
01:25:02.000So if you're minimizing how many calories you put in, then you have a chance of slowing the cancer down so that therapies may have a better chance.
01:25:14.000Let me talk about fasting more generally, though.
01:25:18.000So, for sure, I mean, it's been known for nearly 100 years that if you give mice or rats less food than they would like, then they live longer than they otherwise do.
01:25:30.000And this is certainly the most reproducible and best-studied phenomenon in the whole of the biology of aging.
01:25:36.000Still, there are mysteries about how it works, but a lot of stuff has been found out, and many of my colleagues, including David, have made their careers by making progress, by discovering insights in that area.
01:25:51.000The result of that is that we now have something that people have always recognized to be rather important, namely drugs that trick the body into thinking it's fasting when it isn't.
01:26:02.000They're called calorie restriction mimetics.
01:26:08.000That's also a worthwhile thing because, of course, people like eating, and so, you know, it would be useful.
01:26:14.000Then there are variations on the theme.
01:26:16.000So a guy from close to here at UCLA named Volta Longo, sorry, USC named Volta Longo, has been really the pioneer of intermittent fasting, which is basically properly starving 100%, but only for two days a week or something like that.
01:26:30.000You know, different people have tried different schedules.
01:26:33.000And all of these things are pretty interesting in terms of being good for your health.
01:26:39.000But in terms of increasing your longevity by 30 or 40%, the way they do in mice and rats, no way.
01:26:46.000It turns out, and this is a prediction of evolutionary theory, but it's also been found absolutely clearly in data, that different species react differently to starvation, to fasting, in particular that longer-lived species get less benefit from fasting than shorter-lived species.
01:27:05.000So if you do it just right in nematode worms that normally live like three weeks, then you can multiply their lifespan by a factor of five or more.
01:27:33.000Because there were two studies done, really long, extensive studies, obviously, because monkeys live a long time, and they got different results.
01:27:39.000And so the question is why they get different results.
01:27:43.000If you look closely at exactly how the experiments were done, then it's pretty easy to see that they got different results because of different methodologies, slightly different methodologies, and that the real answer is somewhere between the two.
01:28:25.000First of all, as I say, it is generally good for health.
01:28:28.000You know, you definitely see people getting sick less, you know, regular sickness like infections and so on.
01:28:34.000People seem to stay healthier for a bit longer.
01:28:37.000But in terms of really pushing out the boundaries of these age-related progressive chronic conditions, you know, it's maybe a year or two.
01:28:46.000There's a few other factors that are taken into consideration when people talk about longevity and health, and those are community, enjoyment, friends, loved ones, satisfaction with what you do for a living.
01:29:02.000How do you take those into consideration and what do you think is going on with those?
01:29:06.000Yeah, these things are definitely big.
01:29:08.000So all of these things, and it goes further than that.
01:29:11.000It extends to like meditation and yoga and so on.
01:29:15.000Everything that relates to stress is very important in aging.
01:29:24.000It's reasonably well understood that when you're in a stressed out state, you synthesize elevated amounts of certain hormones that interact throughout the body and in various ways accelerate the accumulation of these various types of damage I was talking about earlier.
01:29:40.000So it's no surprise that there's a mind-body relationship there.
01:31:59.000It's got everything in it that I need for a day or could need.
01:32:03.000And then when I'm traveling a longer trip, I just have one other bag, a sports bag that I'm carrying.
01:32:08.000Is there anything that you think you should be doing that you're not doing that you maybe would like to plan for in the future?
01:32:15.000It's hard to say because, I mean, I do have a lot of freedom about exactly how I spend any particular day.
01:32:22.000I mean, it's more a case of what I would be doing if I didn't have to do the things I'm doing now, which is obviously doing all this advocacy and so on.
01:33:18.000Well, I'm optimistic because you're optimistic.
01:33:20.000When you tell me three to five years from now, we're possibly looking at some sort of a breakthrough where things start moving into the public eye, where people are really taking into consideration, like, this is real technology that we should all start implementing, particularly on people that are older and ailing.
01:33:40.000I mean, at the moment, even though there are some things in clinical trials, We always have to remember that the most challenging areas are still at an early stage.
01:33:52.000And not only do they have to individually get, you know, all the way through clinical trials so that they're safe, but also they have to be combined.
01:34:02.000You know, each of these things individually can be applied to a small subset of the population that happen to have, you know, early onset diseases arising from maybe congenital acceleration of one particular type of damage, right?
01:34:16.000But then to be useful for people who don't have any congenital problems, who are aging at a normal rate, We've got to actually combine them all.
01:34:24.000And of course, that's bound to throw up unanticipated interactions.
01:34:28.000So that's why I put this time frame as far out as 17 years, and even then with only 50% probability, right?
01:34:35.000But the anticipation is the thing that's where the shit's going to really hit the fan, you know, where there's going to be this enormous turbulence in society arising from the knowledge that this is coming.
01:34:45.000I, for one, am very excited about living in V500. I think I can get a lot of shit done.
01:34:54.000I think it makes no sense to think about what one's going to be doing in the distant future.
01:35:03.000There was one time I was on stage about, I'm going to say five or six years ago, and somebody from the audience for about the thousandth time asked me, you know, how long do you want to live?
01:36:06.000I mean, having an idea of how long you want to live, even stating that the quality of life is going to be like a young adult physically and mentally, you know, it's crazy to have an opinion because it's going to be determined by other stuff.
01:36:20.000Well, I'm fascinated by the future in every aspect, technologically, with artificial intelligence, with automation, just the way society is shifting.
01:36:32.000I mean, I'm a very optimistic person in that regard.
01:36:35.000And I think even some of the problems that we have socially, I think those are just...
01:36:42.000A result of this shift towards a more aware, more conscious society.
01:36:52.000So I think that the extending lifespan and getting to see these real exponential changes in our culture and in our society and just our way of life, I'm very excited about it.
01:37:05.000I think it's one of the most intriguing things about being a person is to see how things have shifted.
01:37:12.000I mean, I've been reading a lot of books lately about Native Americans and how they shifted from the early 1800s to the 21st century, the early 21st century.
01:37:22.000200 years later, things are impossibly different.
01:37:47.000I mean, I just think that we are at the cusp of one of the most spectacular eras in human history.
01:37:55.000Things are changing so rapidly and so amazingly.
01:38:00.000Well, of course, the thing that one has to recognize is that we have no particular reason to suppose that they will ever slow down.
01:38:07.000So you can't really call this one of the cusps.
01:38:10.000It's just we're in an exponential scenario and we happen to be noticing it more.
01:38:15.000Since you started off as a coder, we'll wrap this up soon, but I'm going to leave you with this, because I'm really fascinated by artificial intelligence.
01:38:23.000Are you worried at all about artificial intelligence?
01:38:27.000Do you hear the Elon Musks and the Sam Harrises of the world that are sounding the alarm, like, hey, don't hit that switch.
01:38:37.000I think it's a legitimate question, definitely, whether the...
01:38:42.000The progress that we're making might lead to development, perhaps accidental development, of technology that is so autonomous that it gets out of our control.
01:38:56.000However, I do think it's very unlikely.
01:38:59.000I think that the ways in which we have succeeded in making the progress that we have made so far in AI, over the past decade especially, It relies enormously on human-computer interaction.
01:39:14.000In other words, the machines get their information from us and from the world without which they can't make progress.
01:39:23.000I don't see that changing really anytime soon.
01:39:25.000I do still pay some attention to the progress of AI. One of my other good friends, a guy that I knew from way back in my Cambridge days, is the guy who runs DeepMind, which is one of the most high-profile AI companies.
01:39:41.000I'm definitely excited about what's happening, but no, I'm not particularly apprehensive.
01:39:46.000However, I do think that it's better to be safe than sorry and therefore that what's being done to look at the possibilities of things getting out of control or indeed of things just being misused by humans is a very legitimate and valuable area of work.
01:40:03.000Well, Aubrey, the next time I see you, if it's five years from now, I hope you look younger.
01:40:07.000I hope the world has changed and everything's groovy.
01:40:10.000And I appreciate you and I appreciate everything you're doing.