HS 427 FBF - Aging Intervention with Dr. Aubrey de Grey

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My pleasure to welcome Dr. Aubrey de Grey to the show. He is an expert on aging and actually I should say aging intervention. He is a biomedical gerontologist and he is the chief science officer for the SENS Foundation. Dr. Gray, welcome. How are you?

I'm very well, thank You. Thank you for having me on the show.

My pleasure. And you're coming to us from San Jose, California today. But you are based in England, I believe, right?

Well, really, I'm based in both places these days. I travel from one side of the Atlantic to the other all the time, so I have a lot of air miles.

Fantastic. Well, aging since the beginning of time, people have been looking for the fountain of youth. And are we getting any closer to finding it?

Well, of course, it depends quite what you mean by the fountain of youth. But if we just speak generally about bringing aging under proper medical control, in other words, the same sort of level of medical control that we already have today over most infectious diseases, then for sure we are indeed getting closer. I would say that we are within as little as 25 years. Probably. Of course, we can't be certain until it happens, but I'd say we have at least a 50, 50 chance of reaching that level of control over aging within 25 years, just so long as the research that's going on right now is adequately funded and moves forward, a manner that is only limited by the difficulty of the science.

And so when you say bringing it under medical control, the same kind of control we have infectious diseases under now, finally, after all this time, what does that mean? Does that mean stopping the clock? Does it mean living to 120, 150 or 300 years old? Or kind of define that for us, if you would.

Right. What it means is understanding and exploiting the fact that aging is simply the collection of early stages of the diseases of old age. The reason that the diseases and disabilities of old age are of old age, in other words, that they do not affect young adults, is because they are aspects of the later stages of a process that does go on throughout life, but which is initially harmless. And that's the process we call aging. So the types of therapy that we are likely to see in the next few decades that will bring that under control are therapies that actually repair that damage. In other words, restore the molecular and cellular composition and structure of the body, each individual organ and the body as a whole, back to how it was at an earlier age in the closer to early adulthood. So we would typically end up taking someone in middle age or older, maybe 60 or 70, and genuinely rejuvenating them, restoring their structure and therefore, of course, their function, both mental and physical, to how it was maybe 30 years previously. And this would be something that we would do periodically. We would certainly never be able to do a one off treatment that would make Someone completely non aging, such that they would never exhibit any kind of dysfunction or disease, however long they live, Even in the absence of subsequent treatments. But that's not the proposal. The proposal is a periodic treatment that repairs the damage every so often so that it doesn't continue to accumulate to a level that causes these diseases and disabilities.

What is it that's causing us to age? A friend of mine talks about, and I kind of agree that it seems to be that our cells are just copy machines and at some point they just get worn out and they don't replicate anymore. Is that the degeneration process that occurs or is it something else?

There's much more to it than that. There has to be much more to it than that. Because of course, a lot of our cells don't divide. A lot of ourselves just hang out and do what they're supposed to do without dividing. All of our neurons, for example, are like that. And it actually turns out that most of the problems of aging occur in those non dividing cells. Cells that divide have certain problems, but those problems are somewhat easier to solve. So yeah, there's a lot of detail to it. There's a lot of different types of damage that happen. Some of them to dividing cells, some of them to non dividing cells, and of course, some of them to cells in one organ. Some of them a different type of damage in a different organ. But what it's all about here is simple side effects of the normal operation of the machine that we call the human body. And that is really the right way to think about aging, because that brings it down to earth. It focuses on the fact that the human body is just a machine, A ridiculously complicated machine, but still a machine. And that therefore it's no surprise that it should age in just the same way that simple man made machines age as an inevitable side effect of its normal functioning.

So do you have an idea as to where this arresting of the aging process will come from? I mean, did we take a big leap forward when we map the genome?

We certainly have a very good idea about where to move forward. And that's why Sense foundation exists, because we have a particular plan, A plan that I first formulated back in 2000 and which has actually stood the test of time. After a very brief period of refinement, it's more or less been unchanged for the past decade. And this plan essentially revolves around the classification of these various types of damage that I'm talking about into a manageable number of categories, such that within each category, more or less the same type of intervention, same type of treatment, should be able to repair the type of damage. There are various types of damage that we could say that they exist at the cellular level and others at the molecular level. But for each one, we have a very detailed, clear idea about what we need to do to fix it. And of course, in some cases, We're a lot closer than in other cases, but that's okay. In all cases, we know where we're going on this. So that's pretty good news. You know, we actually have a research plan, A biomedical research plan that should get us to this point.

Amaz, so how does that look? I mean, what is it? Is it a combination of factors, or. Tell me about what sensa is doing.

It's only the combination of factors. Yes. So the plan that we have in terms of the classification of the types of damage we need to fix, we normally talk about seven major types of damage, and for each of those types, There's a particular research program, A particular way of fixing it. So to give you just one example, I mean, it would take me too long to go through all of them. One example is cell loss. In other words, cells dying and not being automatically repl by the division of other cells. This happens in various parts of the body during aging, and sometimes is the main factor responsible For a particular type of disease. A nice good example is Parkinson's disease, which is caused by the loss of cells In a particular part of the brain called the substantia nigra. And the way we fix cell loss is very simple. It's called stem cell therapy. Stem cell therapy is all about putting cells into the body. There have been prepared outside in the lab into a state such that they will divide and become the types of cell that have died and not being automatically replaced. So that we restore the number of cells, the cellularity, as people call it, of the organ, so that the organ still works.

So, okay, so restore the cellularity, and we do this through stem cells. Talk to us a little bit about, if you would, the debate over the use of stem cells. What type of stem cells are these?

Well, basically, we're not. The debate about what type of stem cells to use is nearly over. I won't say it's completely over yet, but it's looking like the main problems that existed in terms of identifying cells that could do what we wanted, what we need them to do, but could be obtained in a manner that didn't conflict with certain people's ethics. That problem has gone away because we've discovered other ways of making the Same cells. The big breakthrough was made five or six years ago when a group in Japan figured out how to take normal cells that weren't even stem cells at all and just what you might call de, differentiate them, turn them back into a more primitive state that was very, very similar to a regular embryonic stem cell. And this meant that we could create cells of that nature without destroying embryos. So all of the ethical debate, which was all about the need to destroy embryos, became irrelevant. Now, of course, it's a little bit more complicated than that. Firstly, because these cells are not precisely the same as embryonic stem cells and therefore people are still nervous that they won't quite work as well. And secondly, because you may have, of course, new ethical problems for whatever new way you have for creating a different type of stem cell. But at the moment it's looking like by and large, the problem has gone away.

So that's good. If that has largely gone away, then that's good progress. I mean, what are the big obstacles to this? You know, and I don't want to just talk about the science, the funding obstacles of really speeding up the process of getting to the arrest of the aging process. What do we need to do? I mean, how much money does this take? How much research? And does it come from governments, venture capital?

So the scientific obstacles are certainly daunting, no question. I'm not going to belittle that. But as I say, we do have a very clear plan of action of how to move forward. And furthermore, the leading scientists around the world who are best placed to actually implement this plan, perform this work, are very hot to trot. They really want, they're very enthusiastic about getting going on this. But yes, you're quite right, there is a third ingredient that's required. You don't just need a plan, you don't just need scientists. You also need the resources, the financing to actually do this inevitably expensive work. Work. And that is the rate limiting step right now. I would say that over the past six or eight years, since I've been talking and really advocating on all of this, we've probably moved forward only at about one third the amount that we could have done if funding had not been a limiting factor. And that means we've lost a lot of lives. It means we have delayed the development of these therapies. So you're quite right that it's all about how this money can be obtained. And the way I always look at it is that there are essentially three sources of money, three types of sources of this money. One could be the private sector, venture capitalists, angel investors and so on. But these people tend to want to make their money back quickly. They tend to want an exit strategy that's closer than 20 or 30 years, which is the sort of thing that I'm talking about. So that's a real challenge. We haven't really made much progress in getting the private sector involved, except in those areas of regenerative medicine that are much closer to market. A lot of sense, which is all about regenerative medicine, of course, a lot of sense is earlier stage than that. So then there's the government. Surely they're the people who are supposed to fund early stage work. But unfortunately the difficulty there, I'm sure you're going to want to come back to this in the rest of the interview, is that the general public are very ambivalent about aging. They don't have a good understanding about what treating aging really means and why it really is just medicine, why it really is just preventative medicine for the diseases of old age. And they're ambivalent about it. And of course that means there's no votes in it, and that means it's hard to get governments to do much about it. So as things stand, we have overwhelmingly received our funding from the third potential source, namely philanthropy.

Okay, so philanthropy is really the biggest. That's surprising to me, by the way, because when you say the general public is ambivalent about it, I mean, gosh, you look at this youth oriented culture and it's not just in the, in the States, but around the world. The plastic surgery, the medispas, that the cosmetic industry, I mean, it's a giant, giant industry. Are you saying that the medical version of aging interruption is not a looks thing, it's just a health thing only or when these treatments are applied to people 25 years from now, will they also look younger or just internally be and feel younger?

So first of all, to answer that last part, absolutely. When we get these therapies working, people will look and feel and function just like young adults. It'll be the real McCoy, the real deal, the whole package. But to answer your question about ambivalence, the thing here is that people seem to be happy with the idea that it would be good to age a bit more slowly, to actually be unusually healthy for your age, and then to, you know, to keel over in your sleep at the age of 95 without too much pain. They're up for that. But when we talk about doing the job properly, actually bringing aging completely under medical control, Then there is an extraordinarily ubiquitous knee jerk reaction to think in terms of longevity as the point, you know, of, you know, what would I do with all that time? Or, you know, how would we pay the pensions? Or where would we put all the people? Or wouldn't dictators live forever? These are the things that dominate people's thinking rather than the fact that, hello, we've got a problem today of people getting sick and suffering enormously as a result of aging. So I think really the job for people like me, and indeed for anyone who's interested in promoting this mission. So someone like you, for example, who's taking the trouble to have me on the radio, you know, the job for us is to educate people to understand that this is just preventative medicine for aging, for the diseases of old age. If you don't want to get Alzheimer's, then this is the sort of research that you want to make happen and happen sooner rather than later if you don't want to get cardiovascular disease. It's the same research that we need to hasten.

It seems that, you know, I never thought of the aspect of won't dictators live forever? That's a bit of a scary one. You're right, because ultimately their regimes. Regimes tumble because they die. And you know, many times the new, the new people that take over are not as bad as the one who left. That's an interesting point. But you know, in terms of the pension issue, I mean, that's certainly something that people would initially think. But if they're feeling younger, looking younger, truly being younger, won't they just work longer?

Well, first of all, I want to come back to you on the dictator thing. I didn't say the dictator thing was scary. I think it's one of the most unreasonable reasons to get of all of this. The fact is, dictator does come fairly high on the.

I'm not that concerned about it. I just thought it was interesting that you even brought it up. It never even occurred to me.

I brought it up because other people bring it up, not because I kind of sense it makes no sense. Pensions. You're absolutely right. I mean, there's a reason why we feel as a society that it's reasonable to pay people a reasonable amount of money to do nothing from the age of 65. The reason we think that's a sensible thing to do is because we're very sorry for people who are over 65. And the reason we're sorry for them is because they're about to die. So the whole social contract Completely changes had to be rebuilt from scratch. Square one. When people's amount of remaining healthy life is no longer related to how long they've been alive so far, which is what we're talking about, Right?

Right. Yeah. It's all about that social contract. So that changes the issue of the pensions. I guess the people that would really have a problem is the environmentalists who think that people are destroying the planet. That would be the group that I think would be maybe the big objection. Right.

Well, so you're quite right that there's an enormous amount of opposition based on the problem of, or the perceived problem of overpopulation, which is ultimately what any environmental concern comes down to. It's okay. It's fine to have 7 billion people on the planet. The problem is there are 7 billion people, each of whom is doing significant damage to the planet. So then we have to ask a few things. We have to say, well, first of all, how do we know that's not going to change? You know, supposing 50 years from now we have nuclear fusion as the main source of energy. So then suddenly people have a tiny fraction of their carbon footprint, and that will make a significant difference to how much damage we do to the planet. We also don't know how many children people are going to want to have. We know that fertility rates are going down all the time. We also know that women are having their children later on average, all the time. And of course, when we don't have menopause anymore, which is one thing that's going to happen, then people can have their children later and later without any risk of any kind of genetic abnormality and so on. So there's an awful lot of specifics there that we have to take into account and when we evaluate the potential magnitude of any problem of this nature. But also we have to remember that today we have already a world in which we are making the choice to have fewer kids than we used to, simply because kids are surviving. Two hundred years ago, when people were pioneering the idea of hygiene saving lives, it was rather successful. You know, we went down from having literally 40% of babies dying before the age of one down to a tiny proportion like, you know, 1 or 2%. And if you put yourself back in that, supposing you were Louis Pasteur standing up in front of a general audience, of the general public, and you said, I've got this way of stopping all this infant deaths, and everyone cheers. And then some troublemaker at the back says, hang on, hang on, there's going to be a Terrible overpopulation problem, isn't there? Because all these. Everyone turns around, ask you what your answer is, and if you say it's going to be fine, everyone is going to submit to this barbaric indignity of wearing all these rubber contraptions whenever they have sex, they're not going to believe you.

Yeah, right, right. Or, you know, or the same with Joseph Lister or anybody who's discovered ways to save or prolong lives. But, you know, that actually leads to sort of an interesting question is, are we. I mean, if you look in the past and you look at. There are many people in antiquity or at least hundreds of years ago that lived to be 80, 90 years old. Are we really living any longer or are we just dying less? Because when you look at the hygiene issue and the malaria issues and things like that, those aren't killing people off as much. But the actual top life span, I wonder if it's really gone up at all. I guess, I guess the oldest person has been or is now about 120, is that correct?

So you're absolutely right that the. At least we can't necessarily say that there has been no increase, but we can certainly say that the increase in maximum lifespan is much less than the increase in average lifespan because we have made the greatest impact on diminishing early deaths. The question is what we can learn from this. I think what it tells us is only that the interventions we've developed so far, whether they be actual bona fide medical interventions or whether they be just lifestyle and prosperity interventions that allow people to have a better diet and so on, those interventions have made only a modest impact, if any, on the aging process. And since they've only had a modest impact, we haven't seen extensive increase in the maximum lifespan. But that tells us nothing at all about what we could expect to see in terms of increase of maximum lifespan when we develop new medicines that we haven't got yet, there's every reason to believe that medicines can in principle be developed which will extend healthy lifespan and therefore, as a side effect, total lifespan vastly more than anyone's achieved so far.

What will happen? I mean, I know that you don't know the answer to this yet, but what might happen to one's brain as they are, you know, as the aging process being reversed? Maybe you roll the clock back 30 years, but do they still have all the same memories? And, I mean, I would easily say I would love to be 22 again, knowing everything I know now. And I think a lot of people have felt that way. But I don't necessarily want to be 22 again, knowing what I knew when I was actually 22. I love the wisdom that comes with a few years, for sure.

I assure you that we are not proposing to eliminate people's wisdom and take them back to being, to knowing what they did when they were young adults. The idea here is that memory is a plastic thing already. Memory and every aspect of one's personality and one's wisdom and so on is stored in the brain in a very distributed way. So that, you know, it's not like one factor stored in one neuron or in one synaptic connection. That means that if we were to maintain the structure and composition of the brain indefinitely in a youthful state, there would continue to be this equilibrium where we learn more, we learn new things as we experience them, and we forget other things. But we don't forget everything, of course, because when we recall a memory, that process reinforces the memory. So the things we forget are things that we learned a long time ago, but also they have not been relevant to our lives. So we haven't been recalling them. And that's sort of okay, you know, I mean, I can't remember half the names of the people I went to school with, but that doesn't bother me. So we can imagine that as time goes on, however long we live, there will continue to be this equilibrium. There will be this spectrum of how long ago something happened that we remember. And that spectrum will become more and more spread out. But the things we remember are the things that we want to remember. So it's really not something to be concerned about.

Well, what else should people know about this? You know, I guess maybe. I'd like to definitely get this question before you go. What do you think the treatments will be? I mean, will they be some sort of machine, a magic pill, something that you do over time, maybe by ingesting something in your digestive system? What will happen? I mean, how might these treatments come about?

This is likely to change over time. Actually, it's likely not to be something obvious from the beginning, right at the beginning. When these therapies become available, a large part of it may involve surgery. It may involve replacing whole organs with artificial organs, for example. However, I'm pretty sure that after not very long at all, maybe a decade or so, the therapies will have been improved to the point where it can all be done in a much less invasive, so stem cell therapies, which essentially involves injection into the bloodstream. Gene therapies, which also are done Typically by injection into the bloodstream of, in this case engineered viruses, usually things like that. And indeed some of it, and indeed an increasing amount of it, may just be done by oral administration, as you say. Whether those sorts of things are also vaccines or other more straightforward pharmaceutical interventions, the mode of delivery is going to change over time and it's going to change in the direction of becoming more and more convenient, less and less invasive.

Of all the things that are out now, whether it be vitamin supplements or diet in general or anything else out there, is there any sort of anti aging treatment today? I mean, hgh, different supplementation and things like that? Are any of these things legitimate or are they all just sort of skirting the issue?

I think skirting the issue is probably the right phrase because these things, I wouldn't call them all illegitimate, but they definitely don't get to the root of aging. You don't live 20 years longer or even five years longer as a result of any of these therapies. Unless of course, some people are just unlucky, they're aging unusually rapidly. And there is reasonable evidence that in many cases we can somewhat normalize the person's rate of aging by simple interventions. But if you're already normal, or especially if you're already doing better than normal, then at this point we can pretty much say that there is nothing that will significantly make you better still. And that's why the priority has to be to do whatever we can to hasten the development of therapies we don't yet have.

How do you know if you're aging at a normal rate or if you're above or below normal?

Yeah, that's a great question. And of course, at one level we just don't know, because aging is such a complicated thing with so many ways in which you might die, that in order to decide whether you have what your biological age is, what you're doing is essentially arbitrarily combining a whole bunch of numbers that are semi independent into one number, as if they were, as if that meant something. But still, one can certainly look at all the various things we know about that typically change with age in everyone and ask, you know, where are you on that spectrum? Are you average for someone your age, or are you average for someone younger, or are you average for someone older? And one can get a general idea. I've certainly had such tests, and I'm very pleased to say that for almost all of them I come out looking biologically younger than my chronological age. It's not really robust, rigorous, statistically Meaningful thing, but it's still an indication.

And in the meantime you can go to websites like realage.com right. Again, not very hardcore, but interesting to some extent. Do you have anything to say about that?

Like that or indeed even much more high end tests that one would have? For me, it's not that number that you get out at the end that matters. What matters is the individual data, the specific measurements, the raw data, shall we say, about the various components of aging, because those things will tell you something at least about your risk of particular types of aging, particular aspects of aging that can lead to particular diseases that you might die of.

Sure. Very good. Well, Dr. Aubrey de Grey, thank you so much for this insight today. This is something that we will all be looking forward to and hoping that the future brings great things for life extension and quality of life extension as well. Give out your website at if you would and tell people where they can learn more.

Sure. Yes. I would love the audience to go to our website, sens.org, s e n s for sugar ensforsugar.org and we have there not only the basic information about what the charity does, what work we fund, but also a whole bunch of answers to all the questions you might have about the science and also about the social context of all of this. Also, of course, going there will allow you to contact us directly. Send me an email. Generally get involved. And of course, if you are so minded to contribute financially. We're a charity, we're a 501. So any US citizen gets tax relief on anything they give us. And of course that's how we manage to do what we do.

Fantastic. Well, keep up the good work out there and thank you so much for joining us today.

It's my pleasure. Thank you for having me on the show.

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