by Dr. Heather Sandison , April 1, 2020

Solving the Aging Problem: An Interview with Aubrey de Grey

What follows is a transcript for the podcast: Can Aging be Reversed? Solving the Aging Problem

Sub-section topics within the interview include the following:

Our Society and Economic Systems Benefit From a Healthy Elderly Population
About Aubrey de Grey
Why Aging is a Problem
Research on Damage Repair Modalities to Reverse Aging
Repairing Damage vs. Optimizing Function for Longevity
Categories of Damage Repair for Better Aging & Explaining Stem Cell Therapy
Death-Resistant Cells and Senolytics
Hope for the Future of Anti-Aging Therapies
Longevity Escape Velocity
Predictions for the Future of Human Lifespans
Can Our Planet Support Everyone Living Longer?
Potential Problems for Our World if People Lived Longer
Will Living Longer Cause Overpopulation?
Why Policy Makers Need to Anticipate People Anticipating Living Longer
The Truth About the Future of Aging and Why Researchers Can’t Share Openly
When Will We Live Beyond Genetically Programmed Death?
Economic Benefits of Making New Aging Therapies Accessible and Affordable
How to Solve the Aging Problem: Research Methodology
Respect for the Natural Order as We Progress Technology
Point of Diminishing Returns for the Current Medical Paradigm
About Aubrey de Grey’s Work

Our Society and Economic Systems Benefit From a Healthy Elderly Population

Dr. Aubrey de Grey: The overwhelming majority of medical expenditure across the whole western world these days is of course on the health problems of the elderly. And because of the indirect savings. The fact that the kids of the elderly will be more productive because they won't have to spend time looking after their sick parents. The fact that the elderly themselves will still be able-bodied, and therefore they will be able to continue to contribute wealth to society in whatever way rather than simply consuming wealth, the way things are now. So, any way you look at it, it would be economically completely suicidal for any country not to ensure that these therapies are available irrespective of ability to pay to anyone who's old enough to need them.

Now, of course, it sounds very counterintuitive to an American audience, because of private health care and all that, but that makes no difference. The fact is, whatever your mechanism is for actually allocating the money to make sure that the therapies are available, still, these therapies will pay for themselves so fast that it's going to happen. And there will be this decade or more during which, even if governments have been slow on the uptake now, they will be able to do that forward planning and investment and so on, front loading of...

Dr. Heather Sandison: And I think that the knee jerk reaction... Because the reality is so alternative, right? It's such a different way to think about the world and the future if you're going to live to be 500. But the knee jerk reaction, for me, anyways, is the fear of what could go wrong. But when we take the opposite view of what could go right...

My work as a clinician, I do a lot with degenerative brain diseases, and Alzheimer's in particular, and exactly what you're saying, we see play out every single day at epidemic levels right now, where elderly people become a drain on society, on the caregiver, on their families. They become a liability, not an asset anymore. And if we can improve their health, and they can continue to contribute, then imagine the possibilities of climate change, what we've been talking about. The plastics problems. Rhinoceri in Africa. Right? All of these problems could be solved by people who are at the height of their wisdom and experience, because they still are able to contribute to society. And so, thinking about all that potential, not just day to day the way I do, but as this whole shift in society and the way we plan for the future, is super exciting.

About Aubrey de Grey

Producer: Welcome to Collective Insights. Today, we're thrilled to announce we have with us Dr. Aubrey de Grey. Dr. de Grey is a biomedical gerontologist and is the Chief Science Officer of the SENS Research Foundation, which is dedicated to combating the aging process. He's also the VP of New Technology Discovery at AgeX Therapeutics and is Editor in Chief of Rejuvenation Research, the world's highest impact peer-reviewed journal focused on the intervention of aging. You're going to hear him share how and why technology and scientific advancements will dramatically extend the human lifespan to 130, 150, or even 500 years old, and what that could mean for the world we live in. We're going to dive into the details of the damage repair modalities being developed that offer hope for living longer.

For details on this episode, go to neurohacker.com/podcast. You'll get a summary of our show and can join in the conversation in the comments. You'll also find links to get involved with or donate to the work Aubrey de Gray is leading up at SENS Research Foundation. Last but not least, check out his upcoming conference, Undoing Aging, in Berlin May 21st through 23rd, which is open to the public and tickets are on sale now.

Stay tuned to gain insights on when and how we'll achieve longer lives, and how it will impact our world. Let's jump right in. Here's Heather and Aubrey.

Why Aging is a Problem

Dr. Heather Sandison: Welcome to Collective Insights. I'm your host today, Dr. Heather Sandison, and I am joined by Aubrey de Grey. So, welcome, Dr. de Grey. You have the SENS Research Institute, and that is where you are looking forward at, what do we do about this problem of aging? And you define it as a problem, where a lot of other people just sort of accept that aging, death and taxes, this is going to happen to all of us. So, tell us about your perspective on why aging is a problem and what we might be able to do about it.

Dr. Aubrey de Grey: Yeah. It's really quite extraordinary, when you think about it, that there's any real dispute about whether or not aging is a problem, because the fact is, people don't like getting sick. Disease is generally agreed to be a problem. And the situation we have today is that people who were born a long time ago have problems, have medical problems, right? Now, how is that not a problem? So, the only reason I think why people even think this way at all is by way of really a kind of psychological self-manipulation, essentially trying to put aging out of their minds, because we can't do anything about it yet, and get on with their miserably short lives and make the best of it, and just kind of on the pretense that aging is some kind of thing that is completely distinct from diseases and is somehow off limits to medicine, when in fact that's complete nonsense.

Research on Damage Repair Modalities to Reverse Aging

Dr. Heather Sandison: So, what do you propose we do about it?

Dr. Aubrey de Grey: Well, of course it's not easy, or we would have done it already, but the approach that SENS Research Foundation takes and that I've been taking for the past 20 years is damage repair. So, essentially, aging of the body is no different conceptually from aging of a simple man-made machine, like a car or an airplane. It is simply a fact of physics, not biology, that any machine with moving parts is going to do itself damage as a consequence of its normal operation, and that that damage is going to progressively accumulate and eventually it's going to exceed the amount of damage that the machine is set up to tolerate without decline in function.

So, that's why we go downhill late in life, and the approach that we already successfully implement to maintain machines for as long as we like, if we could be bothered, is of course preventative maintenance. The reason why there exist vintage cars is because cars are relatively simple machines and therefore it is possible with today's technology to actually eliminate the various types of damage, whether it be rust or whatever, that occur, and to do so for as long as we like, so that the amount of rust never gets to the point where the doors fall off. And in the case of the human body, which is of course a much more complicated machine, we simply have to figure out how to do the same thing.

The question is, are we within striking distance of developing a panel of medicines that can actually do that? And 20 years ago, when I first started thinking this way, I realized that yes, we were actually within moderately striking distance of doing that, that all of the various types of damage that we knew about that were accumulating in the body were theoretically amenable to repair by interventions that could be described in quite a lot of detail already and therefore could be implemented, and moreover, that it had been already by that time a very long period, nearly 20 years, since we had last discovered any new type of damage. So, it looked as though we understood, we could characterize, what aging is at the molecular and cellular level pretty thoroughly already. And indeed, over the intervening 20 years since that time that has not changed. We have still not found any new types of damage that we have to come up with some whole new paradigm for repairing. So, things are looking pretty good.

Repairing Damage vs. Optimizing Function for Longevity

Dr. Heather Sandison: So, I want to make this distinction between what you talk about as repairing damage and then what we're doing already in integrative medicine, which is this optimizing function. And to some degree there's some overlap. In my clinic, for example, as a doctor, what I do is I say, "Okay, if there are toxins, that's going to cause more damage, so I'm going to take as many toxins out..." And if there are natural processes that support the repair of damage, like nutrients, having enough nutrients around, certainly NED is one of the things that comes up often, if we can support all of that, then we're going to minimize the amount of damage that occurs. But the distinction here is, what you're saying is, "There's going to be damage that happens. We can't avoid that, but what we can do is go in and repair the damage."

Dr. Aubrey de Grey: Right. So, let me put it this way. A large part of the reason why one has to go into a lot of detail in order to really make the distinction is because we already have in the body this very large arsenal of automatic, built in self-repair machinery. A machinery that goes and repairs damage as it's generated by metabolism. And in fact the only reason that aging exists at all is because that in-built damage repair machinery is not 100 percent comprehensive. If you like, there are gaps in it. There are types of damage that the body generates which do not have corresponding repair machinery. So, the reason why we live longer than mice is because the gaps in our automatic, in-built repair machinery are smaller than the gaps in a mouse's one. And the purpose here is to fill the gaps that remain.

So, the optimizations that you're talking about, like the nutrients and so on, their purpose is to make sure that the in-built damage repair machinery work as well as possible. If there are deficiencies in micronutrients, for example, then even though the machinery is there, there will still be some damage that accumulates unnecessarily, so to speak. But that is distinct from the types of damage that we simply do not have the machinery to repair whatever, and that has to be augmented by medicine one way or another.

Categories of Damage Repair for Better Aging & Explaining Stem Cell Therapy

Dr. Heather Sandison: So, let's talk about some of those mechanisms that you're looking at. So, senolytics come up, the intracellular pieces, the extracellular pieces. Will you take us through those different things that you've outlined as targets for anti-aging?

Dr. Aubrey de Grey: Sure. So, there are of course many, many, many, many different types of damage that accumulate if we go down to the molecular level and the cellular level. But the big breakthrough that helped me to see that this was a tractable problem, not just a theoretically solvable problem, was when I appreciated that we could classify those many types of damage into a very manageable number of categories.

So, I came up with just seven categories that seemed to cover all the basics. And the purpose of this... Of course, just classifying things doesn't solve a problem in and of itself. There are a lot of different ways of putting 1000 things into seven boxes, and you know, so what? Well, the utility of this classification comes when we look at the damage repair modalities, because the purpose of it was to say that within each category there may be many examples, but they're all amenable to repair by the same generic approach.

So, let's take one example: cell loss. So, cells dying and not being automatically replaced by the division of other cells, and differentiation, of course. Now, of course, if that happens, then you progressively have fewer and fewer cells of the given type and you end up having not enough cells for the organ in question to do its job. And if we're talking about the brain, then an obvious example here would be Parkinson's Disease, which is driven by the progressive loss of dopaminergic neurons in the substantia nigra. And all of us have lost maybe a quarter of those dopaminergic neurons that we used to have by old age, but there's enough margin of error in the system that that's not a problem; the problem is for the minority of people who lose maybe three quarters of the ones that they had in early adulthood, and those people have Parkinson's.

All right. So, the obvious fix is stem cell therapy, to manipulate cells in the laboratory into the right state so that we can inject them into the substantia nigra and they will divide and differentiate to create new dopaminergic neurons. And that is in progress right now. There are clinical trials going on to do exactly that. Nearly 30 years ago, there were attempts at this in the days when we didn't know pretty much anything about how to manipulate stem cells before injecting them, and sure enough the result was that it very, very rarely worked at all, but when it worked at all it worked spectacularly well. There are reports of people who were completely free of Parkinson's symptoms for more than 15 years after just one injection, and that was despite not having not having any l-DOPA or anything. So, yeah, so it works.

And of course the point here is that there are other cases. We lose pacemaker cells in the heart, things like that. And the therapies, the stem cell therapies that you would need to do for these different organs, different tissues, will not be the same, but they will have a lot in common. All stem cell therapies have a lot in common. So that means that once we've got a few of them working, working well, then the amount of effort and time and discovery that's going to be required to develop the next one and the one after that will be much, much less, and therefore from a purely medical perspective, from a pragmatic, practical perspective, this classification of a large number of things into this very small number of seven categories is a very important step.

And so I first put this forward in the early 2000s, and it took maybe 10 years for my colleagues to really get their heads around what I was saying, but that's very much happened now. So over the past ten years that have been a series of reinventions of the same concept, talking about nine hallmarks or six pillars or whatever, and it's all the same thing.

Death-Resistant Cells and Senolytics

Dr. Heather Sandison: So, the stem cells are one of these applications. What would be another potential application that we might be seeing already come up clinically? And stem cells are relatively inaccessible to the common person, right? They're extremely expensive, and right now you have to leave the United States to get them. But are there other things that are maybe easier to come by, that someone could use and apply right now?

Dr. Aubrey de Grey: Well, you mentioned senolytics already. So, one of the other six categories that I enumerated back then was senescent cells. Actually, I delineate the category a little bit more widely than that; I say, death-resistant cells. So, this basically means cells that are bad for us and we'd like to get rid of them, and the body does try to get rid of them, with the immune system and so on, and succeeds by and large, but nevertheless some of them kind of resist that and continue to survive and to generally do bad stuff and secrete bad stuff.

And certainly, the most prominent subset of that category of death-resistant cells are these things called senescent cells, which have that name because they have a gene expression pattern that resembles what's called replicative senescence, the phenomenon that was first discovered in fiberglass in cell culture back in the 1960s by Len Hayflick, where he found that cells, if you just make them divide and divide and divide and divide, then they eventually give up and stop dividing, and they don't die, they just sit there and they have various changes in gene expression which have been studied, obviously, a great deal ever since.

So, we see these cells in the body. Chances are that by and large they do not actually arise from excessive replication, but rather from other sources of DNA damage, but that doesn't matter. The point is, they are what they are, and some of them do not get destroyed by the immune system. They do not commit apoptosis. So, we'd like to get rid of them. And in the past decade, I guess eight or nine years, there have been huge advances in doing exactly that, and in particular there have been found existing molecules, both drugs that are already approved and also even nutraceuticals, that are reasonably potent in selectively eliminating such cells. And the benefits seem to be pretty clear, so this is really good news.

Hope for the Future of Anti-Aging Therapies

Dr. Heather Sandison: So, are there things that you suggest people do there, or do you think that this is very individually-based, or do you think that this is going to rescue us? Like, can you live however you want and then start adding things like this later in life?

Dr. Aubrey de Grey: Well, so, first of all, let me emphasize that I'm not an MD, I'm a PhD, so I do not give medical advice. But also, it's clear that this is just one piece of the puzzle. One thing that we can certainly say about this kind of divide and conquer approach of dissecting the damage accumulation problem into these various categories is that every one of these types of damage can kill you pretty much on schedule, on its own, however well we fix all the others. So, we do not want to in any way focus on one particular thing or have some hierarchy of importance. There is no such hierarchy.

However, more than that, we can say that the things that are available today are not particularly effective. They're better than nothing, it seems, they do have some potency, but we definitely need therapies that are more effective. And so, for example, last year, the company that's leading the charge on senolytics, a company called Unity Biotechnology in the Bay Area, was able to announce the results of a phase one clinical trial for a proprietary senolytic that they have developed. They were using it, not systemically, they were just using it on osteoarthritis, actually, so trying to eliminate senescent chondrocytes and synoviocytes. And the effect on self-reported pain was so significant that they were able to report efficacy, even though it was just phase one, and obviously a very small number of patients, and so, I mean, they had to be a bit tentative about it. Phase two is already going on.

So, yeah, but things are looking really, really good.

Longevity Escape Velocity

Dr. Heather Sandison:That's exciting. Okay, so, then, where you really shine is this concept around escape velocity, where, right now, the expected human lives for about 80 years, and some push that a bit and get to 115. But what is really exciting in your research is, what could push that to 150 or to 200? And so, what do you think has to happen in order for people who might be alive today to live to be 150 or 200 years old?

Dr. Aubrey de Grey: So, I am completely sure that the only way that we're going to get past about 130 is by actual damage repair, actually turning the clock back in a comprehensive way. In other words, repairing and eliminating essentially all of the types of damage that we accumulate, as opposed to simply making the body run more cleanly and generate this damage more slowly than it normally would. Because the challenge of doing it that way, of slowing down the generation of damage, is that in order to do so we have to kind of find tweaks to this ridiculously complicated thing called metabolism that don't have significant unintended consequences that stop the body from doing things we need it to do to keep us alive.

And the intractability of metabolism is just beyond imagining. Of course, it's not just that it's incredibly complicated, because you could imagine that could in principle be addressed by really clever computation or machine learning and so on. The problem is that, however clever your artificial intelligence is, it can only find things out on the basis of data that it starts with, and there's a huge amount that we just don't know about how the body works, let alone the stuff that we don't even know that we don't know. So, it's a non-starter as far as I'm concerned.

Whereas damage repair is a vastly more tractable approach. It's something that we can do essentially outside of the specifics of metabolism. The way I like to say it is that it essentially sidesteps our ignorance, because we have to characterize what the damage is, what the differences are at the molecular and cellular level between an older person and a younger person, that contribute to why the older person has less long to live or less long to stay healthy, but we don't have to understand the details of how that damage was actually generated.

Predictions for the Future of Human Lifespans

Dr. Heather Sandison:

So, is there somebody alive today that you think will live to be 150?

Dr. Aubrey de Grey: I think that the chances of people alive today living to 150, or some people alive today living to 150, are very high. I would say at least 80 percent. And I think there's at least a 50 percent chance that some people aged 40 or 50 today will live to 150. Moreover, I believe that really, whatever that number actually is, which of course depends on how soon we develop the technologies, nearly everybody who lives to 150 will also live to 1000.

Dr. Heather Sandison: Say more.

Dr. Aubrey de Grey: Well, this is what you're mentioning, of course, this longevity escape velocity thing. If it's true that the only way we're going to get people to 150 is by damage repair, by bonafide rejuvenation, then we have to ask what that means for buying time, for staying one step ahead of the problem. So, if one is let's say 60 years old at the time that these therapies come along, which is maybe 20 years from now, let's say, and then, these therapies are not perfect, but they're fairly good, then they might be able to rejuvenate that person to being biologically, let's say, 40. Okay? In terms of the amount of damage that's in their bodies still after the therapies have been administered.

Right, now, of course, they're still alive. They're still generating damage, because they're still metabolizing, so that means that over time they're going to carry on accumulating damage. Now, of course, we can carry on administering the therapies as often as we like during that time, but the therapies are not perfect, so there are going to be a certain subset of the damage that they used to accumulate that they're still going to be accumulating, therapy or no therapy. And that means that by the time they're let's say 90, they're going to have as much damage as they had when they were 60, and it's going to be, let's call it the difficult damage, the damage that the therapies don't work on. All right? Which means...

Dr. Heather Sandison: But the technology might be a whole lot better.

Dr. Aubrey de Grey: Well, this is it. In the scenario where they're just continuing to get the same therapies forever, then they're going to get sick, then, eventually, because even though it's only the difficult damage, still, it's going to accumulate to a point that exceeds what the body can tolerate and therefore bad stuff's going to happen and so on. But, as you say, it's been 30 years since the therapies were first administered, which means 30 years of time for people like me to carry on improving the therapy, not only in terms of safety and convenience and cost and so on but also in terms of comprehensiveness. And so that means that by the time this person is 90, we'll be able to give them SENS 2.0, and they still won't be perfect, but they'll be closer to being perfect than they were before, which means we will be able to re-rejuvenate the same people, even though they're now 90, and they won't be biologically 60 for the third time until they're let's say 150. And so on.

So, this is the whole point. And if one actually tries to quantify this, if one tries to ask, "What is the minimum rate at which scientists would need to be improving the comprehensiveness of the therapies in order to stay one step ahead of the problem?" That rate is the thing that I have called longevity escape velocity. Well, it's ridiculously small.

I mean, if we look at any other technology, powered flight or whatever, then of course the predictability of how soon the fundamental, initial breakthrough would be made was impossible. I mean, we always talk about how people like Lord Kelvin would be saying that powered flight was theoretically impossible right up until it was done. But also, conversely, we can say, well, Leonardo da Vinci probably thought that he wasn't 400 years away from actually making the whole thing work. So, there's no way to predict the fundamental breakthrough. But after that, everything's completely different. The incremental advances that are made refining that breakthrough tend to happen at a pretty predictable and indeed pretty rapid rate. It's the same with computers, it's the same with anything.

So, it's pretty much inconceivable that we would fall below longevity escape velocity once we had got as far as getting people up to 150.

Can Our Planet Support Everyone Living Longer?

Dr. Heather Sandison: So, what comes up very quickly after this, and part of the resistance, and maybe why it took so long to get traction on your end is, well, if we think about... It's so foreign to think about living to be 150 or 200, and then you come up with all of these societal things. Like, well, what about climate change? Is there even going to be a world worth living on? What about the generation behind us? Don't we have to make space for them? So, population growth. What do we do with all those years? If we have all these extra years, and the generation before us modeled that you retire at 60 and now we're going to live for another 100 years, 200 years after that, then what do we do with ourselves? Part of it is, we advance this technology so we can live to 1000. We've got to stay on that path. But what are your answers to some of those criticisms, or some of those questions? Because really, they're not exactly critical. It's just, like, "Whoa. Mind blown. What do we do with all that time?"

Dr. Aubrey de Grey: Yeah. So, of course, my first answer is to remind people that this longevity stuff that they're suddenly getting fixated on is a side effect of staying healthy. Because, I mean, let's face it: people die from being sick. And people don't tend to be particularly ambivalent when it comes to staying healthy. There tends to be pretty ubiquitous unanimity that staying healthy is good and being sick is bad. So it's rather important not to actually just mysteriously forget that and start talking about these consequences as if the consequences were the only thing that was on the table here.

So, first of all, it is obviously important to address these questions. You know, how will we stop dictators from living forever? Things like that. But first of all, it turns out that all of these questions are ridiculously easy to answer. I mean, incredibly easy. There are really straightforward reasons why we can easily avoid these problems. Secondly, even if that's not true, even if some of these problems were actually to materialize in a post-aging world, the question is, is there any conceivable scenario in which these problems would be so bad that they were worse than what we have today, with all of these people, the 100,000 people dying every day from aging and the most of them dying after a long period of disease and decline and decrepitude and dependence and general misery? You know, aging is really quite a bad problem. So, one has to make that evaluation, which people just don't. You know, they just completely forget it.

And then of course there's also the question of choice, the fact that we today may have some opinion about whether the problems that would be created as a consequence of solving the problem we have today would be even worse than the problem we have today, but humanity in the future may have a different opinion. Because they may have other technologies that would have minimized the problems that might hypothetically created. And clearly, it's humanity in the future that is entitled to make the choice. So, if we were to say, "Oh dear, overpopulation. Let's not go there," and to delay the development of these therapies, then we would be denying humanity of the future the option, and we would be condemning a whole cohort of people to an unnecessarily painful and unnecessarily early death just because we thought we knew better. Which is bullshit. All right.

Potential Problems for Our World if People Lived Longer

Dr. Heather Sandison: So, I think part of what I heard you just say is those problems are so easy to solve, and one of them...

Dr. Aubrey de Grey: Let me go through them. All right.

Dr. Heather Sandison: Please.

Dr. Aubrey de Grey: So, I mean, just a few of them, just for illustration. So, people actually say, "Oh dear, dictators will live forever." They actually say this, right? Now, last I checked, dictator is fairly high on the league table of risky jobs. Not a lot of dictators die of aging in the first place, in other words, and furthermore, the ones that do tend to have organized their succession beforehand, so it's as if they were already immortal. So, I mean, come on.

Dr. Heather Sandison: Well, no, the one that I really want to stop worrying about is climate change. So, can you just talk about how that is easy to solve? Then I can sleep better at night.

Dr. Aubrey de Grey: Sure. Totally. So, why do we have climate change? People would say, "Because we've got too many people." But that's nonsense. The reason we have climate change is because we have too much pollution. We have too much burning of fossil fuels and too much agriculture and so on. And, hello, we've already got technologies on the way that will be completely ubiquitous and established way before we get these therapies coming along, let alone before the therapies actually have a significant demographic impact. They're going to completely solve that. You know, I mean, renewable energy from wind and so on is already about the same cost to generate as fossil fuels, and getting cheaper all the time because of improved technology. And of course, you've got to worry about energy storage, batteries and so long, but that's also coming down really fast. So, there is no way that fossil fuels are going to carry on even being a thing by 20 years from now, to speak of.

And of course, the same with agriculture. Artificial meat is already a thing, and 20 years from now, for sure and certain, it's going to be both tastier and cheaper than regular meat. So, again, a huge amount of the source of greenhouse gases will just go away, and not even as a result of people waking up and deciding that climate change is actually quite a bad thing, but rather just because people can make money out of it. You know? And this applies across the board in terms of other pollution, whether it's desalination or whether it's plastic-eating bacteria or whatever. So, the whole idea of overpopulation arises not from not having enough space; it's all about pollution, and it's going away. And there's no...

Dr. Heather Sandison: That's very reassuring.

Will Living Longer Cause Overpopulation?

Dr. Aubrey de Grey: Well, sure. I mean, there's no scenario that one can possibly really imagine, when looking at technologies and the rate at which they are coming along, in which the carrying capacity of the planet could in any way fail to rise faster than the population.

Dr. Heather Sandison: There's no way that that could happen?

Dr. Aubrey de Grey: No way. Absolutely no way. I mean, if you look at... You have to obviously quantify what could happen to the population, as well, and it's just not nearly as dramatic as a result of the elimination of aging as people intuitively imagine. First of all, at the moment, as of today, the birth rate worldwide is more than twice the death rate, which means that even today if we just halved the birthrate, people only have half as many kids as they have, then the population would already be going down. And that's why, of course, fertility rates are declining, plummeting, throughout all of the largest countries in the world except Nigeria. The fertility rates are below four in India and Bangladesh and Pakistan and Brazil and Indonesia. So, this is why the UN predicts that global population will peak sometime this century.

Of course, that is on the scenario where we don't have the elimination of aging, but even if we did, the trajectory doesn't actually change all that dramatically. And then also you have to take into account of course fertility consequences of eliminating aging. So, some people will have the knee jerk reaction of saying, "Oh dear, if we don't have aging anymore, then women are going to carry on being able to have kids at any age," which is true, "And therefore we will have an even worse population problem than we would have if we still had menopause!"

But that's nonsense, because if we look at what's happened around the world, every single time that a country has reached a point of sufficient economic prosperity and female emancipation and education and so on to go through this demographic transition where fertility rates plummet, the other thing that changes at the same time is women choose on average to have their children later. Now, of course, only a little bit later, because that's all they can do now, but when they've got the option to delay by another decade and another decade, presumably the same reasons that are making them currently delay by a few years will kick in. So we may actually see an attenuation of population growth resulting from the opportunity to have kids whenever you like.

Why Policy Makers Need to Anticipate People Anticipating Living Longer

Dr. Heather Sandison: Certainly there are a ton of questions and decisions that people make with the consideration of their years of fertility or the years that they're going to live, and all of that basically get scrapped, right? You start over with how you live your life, because the potential just shifts so dramatically, so profoundly.

Dr. Aubrey de Grey: You got it. Yeah. And actually, what I spend a lot of my time on now is trying to get policy makers and decision makers around the world to anticipate that. Because, you see, what's going to happen is... People will often say, you know, "What will people do when they're 500 years old?" And of course I haven't the faintest idea, and I don't care. I think it's a ridiculous thing to be thinking about what people will actually do, because we're not going to have any 500 year old people for at least another 400 years, right? Whatever happens, people are only going to get older at one year per year. And a lot happens in 400 years that we can't exactly anticipate. So this is all ridiculous.

But the thing is that that's not what we need to worry about. What we need to worry about is when people start expecting to live to 500 years, because they're going to want different health insurance. They're going to want different life insurance or pension plans or inheritance arrangements. And these are big ticket items. These are these things that really dominate the global economy at the end of the day. So, when that expectation shifts, people had better be ready to modify the way the global economy works and to provide different products or whatever to match. And that's not going to happen if they haven't been thinking about it beforehand.

So, for me, what matters is, what is going to be the trigger that causes people's expectations of how long they're going to live to shift from what they are today, namely, they're going to live only slightly longer than their parents, into, they're going to live more or less forever? And therefore, how soon is that shift going to happen, and how suddenly is it going to happen? And my answer is terrifying. I think it's going to happen, with high probability, within the next five years, and I think it's going to be pretty much overnight. It's going to be extraordinarily sudden. So, it is a matter of massively high priority for decision makers and policy makers around the world to be what I call anticipating that anticipation, and getting their shit together and understanding what we should do at that point.

The Truth About the Future of Aging and Why Researchers Can’t Share Openly

Dr. Heather Sandison: Certainly. And at that point it sounds to me like maybe it won't be very accessible, kind of how stem cells are today.

Dr. Aubrey de Grey: ...at that point. The point is, this actually happens not as a result of these therapies arriving. The reason why it's going to be so soon is because it will occur as a result of what people like me say on camera and on stage. Now, of course, I already say these things, but I am only one of maybe a dozen experts in the biology of aging who do a lot of public outreach in the media, and the rest of them at the moment, despite being just as knowledgeable as me, do not say those things. The thing is that I essentially... We're all good friends, right? I know exactly why they don't say it. It's not because they don't think it. I mean, maybe they're not quite as optimistic as me, but they're within range.

The reason that you wouldn't know it from what they say is because unlike me, all of them rely for their funding, for the work they do, on governments. They rely on getting grant applications approved through peer review and all that. And of course there's never enough money to go around, so the committees that choose which people are going to get the money and which people are not are constantly, desperately looking for reasons to say no. And of course a very straightforward, nicely ass-covering reason to say no is, "Oh, this person said something irresponsible to some journalist the other day that unjustifiably got people's hopes up." So the result is that my colleagues are extremely keen to err on the side of caution and curmudgeonliness when it comes to what they say.

But of course that whole thing is a balance between what you want to say that's responsible and what you want to say that's true, and the more progress gets made in the laboratory, in mice, not in humans, in mice... The more progress gets made, the more optimistic you're going to be. You know, because it's going to be a balance. So, that center of gravity of what the expert communities say is going to shift.

Dr. Heather Sandison: Well, and it already has, right? What you were...

Dr. Aubrey de Grey: Well, you're so right. You're so right. I mean, the example I like to give these days is my good friend David Sinclair, who's definitely one of these dozen people, same as I am. He wrote a book that came out a few months ago. It was called Why We Age And Why We Don't Have To. Now, I will tell you that as little as five years ago, David could not have written a book with that title and kept his job. He's a professor at Harvard.

So, things are changing already, but they haven't yet changed to the point where people have kind of started to get their hopes up. Because this whole irrationality that we see in society, where people forget about the health aspect and they only think about these things that they can be worried about, this is all a psychological self-manipulation. It's all a matter of putting this out of your mind and getting on with your miserably short life and trying to pretend that aging is a blessing in disguise so that you don't have to be preoccupied by this terrible thing that's going to happen to you. And of course, that only makes sense, even psychologically, let alone rationally, for as long as the prospect of something actually happening is still negligible. When it becomes distinctly non-negligible, it becomes appropriate to actually absolutely get your hopes up and get emotionally invested in it and agitate to hasten the defeat of aging.

And that is the transition that's going to occur, and based on the rate of progress in the laboratory, as I say, in mice and suchlike, and how far I think we have to get before my colleagues will start saying really quite optimistic things to camera, that's not very far. So that's why I say chances are five years. The actual therapies probably won't exist for more than 15 years from now. And that's good, that we'll have that decade or more of preparatory time, but still, it's going to be a very turbulent period, because of these shifts that are going to happen in big ticket items that people are going to be changing their minds about.

When Will We Live Beyond Genetically Programmed Death?

Dr. Heather Sandison: And so, you're thinking in the next five years, in the lab, in rats or in mice, we will have the technology to help them to live at this rate that's past their genetically programmed death, or life.

Dr. Aubrey de Grey: Yeah. Let me elaborate a little bit on that. So, we are not going to reach this thing, a longevity escape velocity, in mice, because it's harder to reach longevity escape velocity in a shorter lived organism than in a longer lived organism. Right? Because you've got less time to make the next improvement to the therapies.

Dr. Heather Sandison: Well, and also there's not a ton of interest in keeping mice alive forever.

Dr. Aubrey de Grey: That's also true, but even if we take that out, still, it's technologically harder because you've got less time to make the next advance. But what we will do, I believe, is we will get mice to live maybe a year, year and a half longer than they normally do, and of course that extra time will be healthy time, and here's the critical point: we will do it by rejuvenation therapies. In other words, we will do it by applying therapies to mice that have had exactly nothing done to them until they already reach middle age.

Dr. Aubrey de Grey: We can already get a year, year and a half out of mice if we genetically modify their ancestors so they are born with, for example, no growth hormone receptor. So, they're very small, and we have to keep them very warm, but they do live a hell of a lot longer than their siblings.

Dr. Heather Sandison: And the young plasma exchange, that piece in mice has also worked to...

Dr. Aubrey de Grey: Yeah. That hasn't given significant life extension. It's definitely shown a number of... And we funded some of this work. We've definitely been able to show that, and rejuvenate certain aspects of aging in older mice and rats doing this kind of thing, but it's not by any means comprehensive enough to actually give significant life extension.

Dr. Heather Sandison: So, I want to go back to your time frame and the predictions here. Because you've been right. 20 years ago, you were saying things that are now coming to fruition. So, I'm curious, and I won't hold you to this 100 years from now when we're having another conversation, but... The next five years you think the technology will be there for mice, that we'll significantly shift things so that then the expectation for humans shifts and we start having more of those conversations because of the optimism. And then, the technology to shift from mice to humans, you're predicting about 15 years for that science to kind of catch up and for there to be actual therapies available. And...

Dr. Aubrey de Grey: That's right. Now, first of all, I do want to emphasize how speculative these time frame predictions of mine are.

Dr. Heather Sandison: Of course.

Dr. Aubrey de Grey: So, when I talk about five years for mice, even that is fairly speculative, but if we're talking about 15, 20 years for humans, that's ridiculous. So, I think that that is the time frame within which we have a 50/50 chance of getting to there, but I always like to emphasize I think there's at least a 10 percent chance that we won't get there for 100 years, because there's all manner of possibilities and unforeseen obstacles.

Economic Benefits of Making New Aging Therapies Accessible and Affordable

Dr. Heather Sandison: Of course. And then, when we do get there for humans, initially it's going to be extremely expensive.

Dr. Aubrey de Grey: Not necessarily. Because here's another thing that's going to happen during that anticipation period: people are going to know that it doesn't matter how wonderful these therapies are unless they can actually get them. So, the imperative that is going to be imposed upon governments and so on will not only be to throw lots of money at the research to hasten the development of the therapies, but also to throw lots of money at infrastructure and training of medical personnel and so on and so forth to ensure that the therapies are widely disseminated as soon as they can be.

Now, there are two things that are important to take into account in that regard. One of them is the electoral imperative. You know, if it's going to be possible to get elected unless you have a manifesto commitment to have a war on aging... And I mean a proper war, I don't mean just like the war on cancer, which was of course, you know, it troubled the NCI budget, but it was imperceptible to the US taxpayer. I mean proper wartime kind of expenditure. So, there's that.

But also, there's the economic imperative, the fact that these therapies will unquestionably pay for themselves many times over really quickly, because the overwhelming majority of medical expenditure across the whole western world these days is of course on the health problems of the elderly. And because of the indirect savings. The fact that the kids of the elderly will be more productive because they won't have to spend time looking after their sick parents. The fact that the elderly themselves will still be able-bodied, and therefore they will be able to continue to contribute wealth to society in whatever way rather than simply consuming wealth, the way things are now. So, any way you look at it, it would be economically completely suicidal for any country not to ensure that these therapies are available irrespective of ability to pay to anyone who's old enough to need them.

My work as a clinician, I do a lot with degenerative brain diseases, and Alzheimer's in particular, and exactly what you're saying, we see play out every single day at epidemic levels right now, where elderly people become a drain on society, on the caregiver, on their families. They become a liability, not an asset anymore. And if we can improve their health, and they can continue to contribute, then imagine the possibilities of climate change. What we've been talking about. The plastics problems. Rhinoceri in Africa. Right? All of these problems could be solved by people who are at the height of their wisdom and experience, because they still are able to contribute to society. And so, thinking about all that potential, not just day to day the way I do, but as this whole shift in society and the way we plan for the future, is super exciting.

How to Solve the Aging Problem: Research Methodology

Dr. Heather Sandison: So, if you could do any research project in the entire world, no budget, but you wanted to answer one question, how would you set that up? What question would you answer?

Dr. Aubrey de Grey: We don't really think in terms of answering questions, and the reason we don't is because no new questions seem to be coming up. People often say, "Why don't you write another book?" Because I've written this book about all of this for a relatively general audience in 2007. You know, it's quite a long time ago, and obviously an awful lot has happened in the meantime, so it kind of would make sense.

But the thing is that pretty much everything that's happened is pretty much what we predicted in that book. You know, when I split aging out into these seven major sub-problems, that was early 2000s... We have not had any problem number eight come along in the meantime. We haven't even had some new discovery that shows that our proposed solution to one of the seven problems was actually not going to work, and we had to start from square one. That hasn't happened either. We're still pursuing the same general approaches. And so, it looks like this whole paradigm is standing the test of time really well. Of course, there have been unexpected developments, but none of them have been bad surprises. They've all been good surprises, like, you know, suddenly CRISPR. Things like that.

So, yeah. We don't really answer questions. What we do is, we plod along figuring out the technical minutiae that actually allow our existing answers to be implemented.

Dr. Heather Sandison: Interesting. I ask that question a lot, and I've never gotten an answer like that and I appreciate it.

Dr. Aubrey de Grey: For me, a lot of it actually comes down to the psychology of discovery. Because a large part of the reason why I got into this field... I was originally a computer scientist until my late twenties. Why I got into this field was my discovery that almost all biologists thought that aging was kind of not their problem. They would say, "It's not very interesting. It's not very important." And I would say, "Why?" And they would say, "Well, you know, it's just decay, isn't it? What kind of fundamental truths about the universe are you going to discover by studying decay?" And I would say, "Well, sure, but it's bad for you." And they would say, "Well, that's not my problem." And I would say, "It kind of is."

And I mean, there's a real fundamental distinction, I believe, between the mindset and the mode of operation of basic scientists, who do answer questions, of course, as opposed to technologists. Basic scientists are all about understanding nature and technologists are about manipulating nature. And the way they go about it is fundamentally different. You know, the way you use evidence is different. When you're trying to discover stuff, you're always looking for the most direct evidence, to come up with the next hypothesis and so on, whereas pioneering technology relies entirely on leaps of faith, on putting two and two together and making 17 and seeing what happens.

And I mean, it just doesn't compute. What really doesn't compute is the idea of sidestepping one's ignorance that I mentioned earlier. The idea of actually knowing enough. There's no such thing as knowing enough when your whole raison d'être is finding things out for the sake of finding things out.

Dr. Heather Sandison: So, when you sort of sidestep, again, and go into this world of technology and apply it to health, it feels like when we've done that in the past we've come up against a lot of, like you said, the unknown unknowns. There are a lot of unpredictable consequences of this that we just, they're unpredictable, right? By definition. So, what about all of that? We've talked about it a bit, but...

Dr. Aubrey de Grey: The way I look at it is this. Yes, undoubtedly, medicine is fundamentally black magic, because of the vast amount that we don't know. But yet it works. People are living longer and healthier now than they were before, and a lot of the reason why is medicine. So, I figure, it's okay.

Dr. Heather Sandison: We'll cross that bridge when we get there?

Dr. Aubrey de Grey: We are constantly crossing bridges of that nature as we go, and that's fine.

Dr. Heather Sandison: And so, there's a lot of confidence in what you're saying. You've been predicting this for a long time, a lot of it has come true, and the surprises that you've found you say are usually positive.

Dr. Aubrey de Grey: Always.

Dr. Heather Sandison: Or always positive. Okay, there's a ton of confidence in that.

Dr. Aubrey de Grey: Well, I mean, I'm just talking about the past, not the future, right? I'm saying in the past two decades, since I started thinking and talking this way, no bad news had happened.

Respect for the Natural Order as We Progress Technology

Dr. Heather Sandison: All right. All right. And I have the other... You can probably feel that I'm a little nervous about all of this. I have a lot of trepidation around, if we shift things so out of the natural order... I'm a naturopathic doctor, right? So I have a lot of reverence for the natural order of things and the way that the universe and the world, the planet, works, and that there are some things that I think we may not ever fully understand, but that doesn't mean I don't have respect for them, and I don't think that there's a lot of value in that. And so, if we completely shift gears and apply this type of technology to the human body, what might we run up against? Or do you just completely reject that?

Dr. Aubrey de Grey: I don't reject it at all. I think we absolutely need to keep our eyes open with every step that we take to look out for unintended consequences that we can then preempt and avoid and deal with, either by going in a different direction with different medicine, or by developing an adjunct medicine that addresses the side effect, or whatever. But that's no different from the way that we do medicine today already.

Point of Diminishing Returns for the Current Medical Paradigm

Dr. Heather Sandison: Yeah. And I guess I would argue that the way we do medicine today conventionally really is not working, that people are quite sick, that most of America, certainly, is sick, is overweight, depressed, we're very heavily medicated, and that my great-grandparents lived longer than my grandparents, and that this generation that's coming up on death will probably live less long than the generation before them. At least in my family, and I know that's different in different families. But there are degrees of pollution and toxicity and things that are making us quite sick at a societal level.

Dr. Aubrey de Grey: Okay, so let me talk about that.

Dr. Heather Sandison: Yeah, thanks.

Dr. Aubrey de Grey: So, I would say that, when you compare your grandparents to your great-grandparents, that's a surprise. I would say that your family is an exception in that regard. Most people's grandparents lived longer than their great-grandparents. Now, today, you're absolutely right. The statistics say that life expectancy is leveling off in the western world, and in fact the US is the first country that has had a detectable reduction in longevity year on year, though I think they've actually recovered again this year.

But all that says is that we have reached the point of diminishing returns for the current medical paradigm. So, the only reason that we've had a continuing increase in life expectancy across the industrialized world since World War 2 is because we were able to do things over and above the things that increased life expectancy between, let's say, 1880 and 1950. Now, during that period, of course, the reason why life expectancy was going up was because we were getting better and better at stopping people from dying young. In the early 19th century, even in the wealthiest countries in the world, around 40 percent, four zero percent, of babies would die before the age of one, and of course there was lots of death in childbirth and so on and so forth, and that was pretty much gone by World War 2. So, if nothing else had come along at all, then we would have seen a leveling off then.

Now, of course, the rate of increase that we've seen since World War 2 in the industrialized world has been slower than what it was in the first half of the 20th century, but it's still been quite significant, and the reason for it, most people think, is mainly that the people who are dying are people who were born in and who spent their early life in situations of gradually increasing prosperity. The average family was more prosperous in let's say 1930 than it was in 1890. And prosperity translated into better nutrition, especially better prenatal and perinatal nutrition; that period is extraordinarily important, in fact, because of course there's lots of chaotic cell division and stuff going on that can lay down damage, and it better be done right. So, relatively modest deficiencies of micronutrients can end up putting one in a situation of essentially accelerated aging early in life, which stays with you throughout life.

So, of course there's contributions from reduction of smoking and other things like that that have also made a difference, but most people think that the number one contributor why people live longer now than they were in 1950 in the industrialized world is better prosperity. So, of course, that is again something that's going to hit diminishing returns, and I think it's fair to say that right now, that's exactly what we're seeing. That other stuff, like the obesity epidemic, is now at parity, more or less, with the residual very slight gains that we're making from past prosperity. So nothing's going to happen until we get the next paradigm, which of course is the stuff we do, rejuvenation technology.

About Aubrey de Grey’s Work

Dr. Heather Sandison: So, where can people learn more? Undoing Aging is a conference that you're involved with.

Dr. Aubrey de Grey: Well, I run it.

Dr. Heather Sandison: Yeah. Your conference. Thank you for clarifying. So, can you tell people a little bit about that? Is it open to the public? Who...

Dr. Aubrey de Grey: Certainly. It's open to absolutely everybody. It's in May this year, in Berlin, May the 21st through 23rd, and it will feature a wide variety of absolutely cutting edge science as well as stuff that is already available to the public. We have a whole session called Rejuvenation Now.

Dr. Aubrey de Grey: The other place that of course I would recommend people to go is our website, sens.org, S for sugar, E for elephant, N for November, S for sugar, dot O-R-G. And it is written for everybody. There's material there for people from complete novices all the way up to absolute experts in the biology of aging, and of course lots of news, not only about our own activities but about activities around this whole field. And you know, it's a pretty good place to start.

Dr. Heather Sandison: Fantastic.

Dr. Aubrey de Grey: Oh, and of course there's also a nice, big, friendly donate button on the front page.

Dr. Heather Sandison: Thank you so much, Dr. de Grey. It's been an absolute pleasure having you on the show, and I've learned so much. It really is mind blowing to talk to you and to hear about this potential that sounds like it may show up in our lifetime. So, fantastic.

Producer: Thank you so much for being with us for this conversation with Dr. Aubrey de Grey. If you didn't know already, one of the other things we do in the collective is create supplements for better cognition, better aging, and more energy. If you're looking for any or all of that, go to neurohacker.com to learn more, and as our gift to you we're offering an additional 15 percent off your first order using the code podcast61. If you have any questions about this content, please leave them on our site at neurohacker.com/podcast, and we'll work to get those answered by Aubrey on a future episode. Make sure to go leave us a five star review and subscribe to our podcast, and we'll see you next time.