Aubrey de Grey (@aubreydegrey) is Cambridge researcher and Chief Science Officer of SENS Research Foundation focused on aging and extending human longevity. He proposes that the first human beings who will live to 1,000 years old have already been born. In addition to his research, Aubrey is editor-in-chief of the academic journal Rejuvenation Research, author of The Mitochondrial Free Radical Theory of Aging (1999) and co-author of Ending Aging (2007). De Grey’s research focuses on whether regenerative medicine can prevent the aging process. He works on the development of what he calls “Strategies for Engineered Negligible Senescence” (SENS), a collection of proposed techniques to rejuvenate the human body and stop aging. To this end, he has identified seven types of molecular and cellular damage caused by essential metabolic processes. SENS is a proposed panel of therapies designed to repair this damage. He has been interviewed by most major news sources, including CBS 60 Minutes, the BBC, The New York Times, Fortune Magazine, The Washington Post, TED, Popular Science, The Colbert Report, Time and the Skeptics’ Guide to the Universe. [spreaker type=player resource=”episode_id=18590674″ width=”100%” height=”200px” theme=”light” playlist=”false” playlist-continuous=”false” autoplay=”false” live-autoplay=”false” chapters-image=”true” episode-image-position=”right” hide-logo=”false” hide-likes=”false” hide-comments=”false” hide-sharing=”false” hide-download=”true”] Subscribe onApple Podcast | Google Podcast | Android | Overcast | Spotify | YoutubeYou can listen right here on iTunesIn our wide-ranging conversation, we cover many things, including:
Why Aubrey switched from studying AI to the science of human longevity
The causes of aging and how we can “cure” them
Why prevention is orders of magnitude more effective than intervention
The reason Aubrey believes some humans today will live to be 1000 years old
Why there isn’t enough funding or support currently for fighting aging
The reason stem cell research is progressing rapidly and proving fruitful
How caloric restriction effects metabolism and aging
Why SENS often spins out businesses to further their aims
The science of immortality
How mainstream media has reacted to prospect of increasing lifespan
Transcript
Producing this podcast and transcribing the episode takes tons of time and resources. If you support The Disruptors and the work we do, please consider making a tax-deductible donation. If you can’t afford to support us, we completely understand as well, but an iTunes review or share on Twitter can go a long way too! AUBREY DE GREY: Well I do think it’s very probable. In fact, I think it’s quite likely that the first person to live to a thousand is already in their forties or fifties—or, and perhaps even older. So the question is, “Why do I think that?” And a lot of people misunderstand this. Some people think that the reason I’m saying this is because I think that we are within a small number of decades of developing therapies that completely, one hundred percent eliminate aging by repairing every single aspect of the damage that the body accumulates as a side effect of its normal operation. I don’t say that at all. I never have, and I never shall. MATT: Survival of the fittest—Darwin realized evolution is merely the process of survival. Nothing has been more driving a force as survival. Nothing wants to die. I don’t want to die. You don’t want to die—even if you’ve accepted death. When there’s a way around it, we would give anything. Today we’ve got Aubrey de Grey. Aubrey’s the Cambridge researcher and chief science officer of the SENS Research Foundation. They’re focused on aging and extending human longevity. He thinks that today humans are alive who’ll live to be a thousand years old. The first have already been born. Is it you? Is it me? Find out. Aubrey is the chief editor of the academic journal, “Rejuvenation Research”. He’s the author of “The Mitochondrial Free-Radical Theory of Aging” and the co-author of “Ending Aging”. He’s given some incredibly successful TED Talks and has been interviewed on most major news sources including: “CBS”, “60 Minutes”, “The BBC”, “The New York Times”, “Fortune”, “The Washington Post”, “TED”, “Popular Science”, “The Colbert Report”, and “The Skeptic’s Guide to the Universe”. he’s been everywhere and more. And makes sense! His non-profit is focused on extending quality human life and helping us all live longer. And he thinks—you know what? We can do it. This is an incredibly interesting interview—something I, personally am very passionate about and I would say all of us are. If we can get extra years on our life, especially good quality years, we would give—well, anything—as long as you don’t die, right? Today we discuss why Aubrey switched from studying artificial intelligence to the science of human longevity; the causes of aging and how we can cure them; why prevention is orders of magnitude more effective than intervention; the reason Aubrey thinks that we will, in fact, live to a thousand; why there isn’t enough funding or support, currently, for fighting aging; the reason stem cell research is progressing rapidly and proving very fruitful; how caloric restriction affects metabolism and aging; why SENS often spins out businesses to further their aims; the true science of immortality; and how mainstream media has reacted to the prospect of increased life-span. And now, without further ado, I give you Aubrey de Grey. So Aubrey, when did you first become obsessed with aging?AUBREY DE GREY: So yeah, it wasn’t when I was young, actually. Because when I was young I was laboring under a fabulously tragic misconception. And the misconception was that everybody realized that aging was the world’s most important problem—and the problem that could potentially be solved by a medicine of the future, and we should be kind of working to make that happen as soon as possible. This was completely obvious to me from my earliest days. And I just never did the experiment of actually asking people, you know, whether they agreed with me. The idea that they wouldn’t was like the idea that they wouldn’t think the sky was blue. So it was actually not until my late twenties that I started thinking about this. I had, by that time, forged a pretty successful career for myself in artificial intelligence research. And I was perfectly happy doing that. And then I had—when I was twenty-six I met, and shortly afterwards married a biologist who was a lot older than me. She was a senior professor already. And through her not only did I learn a lot of biology—I also discovered, you know, gradually began to realize—that we were never talking about aging. And I started asking questions and it turned out that she wasn’t actually very interested in aging. She thought it wasn’t very important. And it wasn’t just her, it was all the other biologists I was meeting. So, you know, it was a complete revelation to me—and a very tragic one—to discover that actually, no, almost everybody in the world was mad and was taking the view that aging is something we should make our peace with. And so eventually after a couple more years of coming to terms with that I decided I had to switch fields. And here I am.MATT: And it’s the problem of, when you’re getting attacked, don’t ask someone for help—don’t ask everyone for help, ask someone for help. Is the tragedy of a common scenario, or is it just something that people thought was quite literally impossible? AUBREY: I think it’s a multi-layered thing, actually. Certainly, I believe that almost everybody had convinced themselves—and indeed, of course, still today, we haven’t by any means completely solved this problem—had convinced themselves that aging is absolutely inevitable. But the medical control of aging, of the same—on the same scale that we can medically control most infections with something it can to create into perpetual motion. Well on top of that, people had also convinced themselves—and again, this is a problem that still exists in a big way—that aging was some kind of blessing in disguise. You know, that there was some kind of, you know, huge amount of tragedy that would occur if we, by some miracle, did actually eliminate aging, that it probably would create as a result, would be even worse. And all of this has, of course, been built up over the history of civilization, and I believe that it’s been built up as a result of our knowledge that aging is this absolutely ghastly thing—and our psychological need to put it out of our minds. And even today, when obviously medicine and medical research is advancing so rapidly, people are still—you know, with some justification—very hesitant to get their hopes up. And you know, it’s all very well getting your hopes up, if “you don’t mind your hopes being dashed because at least you tried” kind of thing. Which is my attitude—but of course, a lot of people take the view that having one’s hopes dashed is really not much fun and therefore they’d prefer not to get them up in the first place. And that is a huge part of the problem that we face today.MATT: That’s the eighty-twenty scenario: twenty percent of people will take action; eighty percent will just sit by and hope. So you’re you’re taking action now—talk to me a little bit more about SRF—what you guys are focusing on, and what the cutting-edge is when it comes to human longevity?AUBREY: Sure. Well I mean, first of all, let me actually come back on what you just said. If twenty percent of the population actually were getting up and doing things, then my job would be done. If twenty percent of a percent were doing so, my job would be done. Unfortunately we have to rely on a very very small minority of people who are pushing this forward.MATT: Hey Matt here. This the purpose of Fringe FM: To get on the point-zero-one percent of people that are transforming the world—transforming society in our collective future. To highlight them, and to try to inspire others like them—to get in on the game and to try to help us improve our collective future. If this sounds interesting for you I recommend reaching out to Aubrey. Or if you’re focused on other things entirely, just put in the effort. Now let’s jump back. AUBREY: And SENS Research Foundation—which is the 501(c)(3) public charity that I helped to create a decade or so ago—is still leading the way in this area. We absolutely pioneered the whole field of research on what we like to call “comprehensive damage repair” as an approach to medically controlling aging—which essentially consists of a divide and conquer approach of identifying a manageable, but still, you know, a non-trivial number of of types of damage that the body does to itself throughout life—and figuring out and developing ways to to repair that damage, so as to put the molecular and cellular structure of the body back into a state resembling how it was at an earlier age. And so we continue to have a variety of different projects. Some of them we pursue internally at our research center in Mountain View, California. A lot of them we pursue extramurally, so to speak—in other words we support laboratories and internships in universities that addressing some of these problems. And what I am very happy to be able to say is that over the past few years we have augmented all of that with the private sector. In other words, we have been able to take a succession of projects, so far, five—to a point of sufficient group of concept—that we’ve been able to spin them out. We’ve been able to get investors interested. Obviously, not any old investor. It really is very much the more visionary, “high-risk, high reward” types, the angles. But yeah, getting investors interested enough that it’s been possible to create companies and get people involved who are you know, I guess not fond of giving money away and whose whose whose pockets were not actually being emptied in our favor as a non-profit but who are willing to get involved even in a very speculative, actual investment.MATT: Yeah you’d pay anything to have an extra day—and extra year, on your life. So I imagine you’re doing very very well, especially with Silicon Valley today. You talked about the different types of damage that comes to both body, and I imagine, mind. Can you break down a little bit more what aging actually looks like on on your perspective?AUBREY: Body and mind, certainly. Or perhaps, more accurately, body and brain. You know, and that’s important to say because it’s important to know that the brain is made of more or less the same stuff as the rest of the body. And therefore, the same basic idea—it’s the same conceptual technologies—can be applied to the brain as, in the rest of the body. We certainly don’t want to end up in a state where we have rejuvenated the body really well but we have not rejuvenated the brain. But there is no real danger of that happening because the same technologies—the same ideas—can be applied. So what are these types of damage? Well, normally we divide the damage into seven major categories. We talk about things like cell loss. In other words, cells dying and not being spontaneously replaced as they die, by the division of other cells. This is a very generic idea of course. But it’s a concrete idea, it’s not just a theoretical, abstract thing. It really does happen in a variety of different tissues. And it happens progressively during life. So of course, eventually one ends up with an affected tissue and not having enough cells to do its job. And we all know what we can do to fix this. We simply inject stem cells, which are prepared in a laboratory into the right kind of state. So that they know what to do, to divide and transform themselves—differentiate, as we say—into replacements for the cells that the body is not replacing at the time. Simple idea, of course much easier said than done and that’s why there’s so many researchers out there doing stem cell therapy. But, of course the other reason why there are so many people out there doing stem cell research is that it is an established field. It’s something that people get. And therefore, they’re willing to put money into it. Whether it’s public money or private money. The reason why SEMS Research Foundation exists is because most of the other categories are not so fortunate. They are much less well-understood and appreciated—in particular, the type of damage may be appreciated but the approaches to repairing the damage may not be—and therefore we’ve had to step into that bridge and cross that “valley of death” and put, you know, work into developing at least the early stages of therapies that repair the other type of damage.MATT: How much is your work held back by religious values and politics?AUBREY: Well, okay, let’s do those two questions separately—religious values, one, and then politics. So religious values, very little—it may, that may change, you know—it may be that as this begins to really grow and become, you know, become a big deal in society overall; much less the problem but the solution; that there is more debate in this area. But so far what’s happened is that insofar as religious people start to think about this and start to be concerned that this is even somewhere, you know diverting God’s plan or whatever—that it’s actually rather easy to change their minds. My standard approach is to say: “Well look here—the idea here is not to extend life—the idea is to extend healthy life. And of course we know, and we do not want to shy away from the fact that extending a healthy life will have a side effect of extending life on average—but, all that means is number one: we are alleviating suffering. You know, we are doing exactly what the Holy Scripture—whether it’s the Bible, or the Quran, or whatever—tells you to do. We are actually improving people’s quality of life which seems to be the right thing to do. So you can certainly argue that it would be a sin not to be working on this. Secondly—you know, insofar as this could be considered to be disrupting God’s plan—well you know, last time I looked God was supposed to be omnipotent, right? So you know, He can perfectly well strike you down with a thunderbolt however healthy you are. So you know, it’s very hard to make an argument that we’re in any way usurping God in this. MATT: What about with stem cell research? I know that’s not mainly your topic.AUBREY: No no no, great example! I mean, stem cell—we don’t do stem cell research very much. But the only reason we don’t do it is because other people are doing things that are needed. So we very much regard stem cells as an indispensable component of this. But what you have to remember is that religious groups were never against stem cell research or stem cell therapy, per se, at all. The only thing they were against were the use of stem cells that were derived in a particular manner that involved destroying embryos. Now today that’s basically completely irrelevant, and completely side-stepped because we have this thing called IPS: Induced Pluripotency where you can take a cell that isn’t a stem cell at all and you create cells that are almost exactly the same in terms of their behavior, as the cells that were being got from embryos—without any embryos being involved. So the whole ethical issue that underpinned the politics around stem cells and over a century, you know—has completely gone away.MATT: When when did that come around? And how how close are you working with people in related fields—say, say clean meat manufacturing, synthetic biology, etcetera—that are focused not on extending life but on similar, similar systems? AUBREY: So first of all, wind it up yes come along it was really kick-started by one paper that was published by a Japanese group, the group Shinya Yamanaka in 2006 and it exploded. It was like—it turned out that the techniques that Yamanaka had very painstakingly identified and developed were very easy to replicate in other labs. Very often that’s not true—you get a breakthrough that would actually take a long time for people to figure out the intricate details of how to get it to work in their own hands. But that wasn’t the case for this. So yeah, IPS is—is you know, really really game-changing and it’s been around for more than a decade now. Sorry, what was your other question again?MATT: The other question was how close are you in working with other people that are working in related fields, say clean meat?AUBREY: So the second answer is we’re not really working closely with them. We don’t have formal links with people working in, for example, artificial meat. But, I do certainly pay strong attention to those groups. And also, for that matter, to groups not necessarily working in biotech per se—but in other transformative technology like artificial intelligence and renewable energy and so on. And the largest part of the reason I pay attention is not just recreationally because it’s a personal interest; but because the progress that is made by those groups in those areas will actually play a big role in ensuring that when we do bring aging under medical control we will not create new problems that are really difficult to address. So for example let’s just take overpopulation. People say, “Oh dear, where do we put all the people” you know—we’ve got this problem of climate change and so on today, you know because of too many people; you know it’s going to get worse if people are not dying anymore. And of course that’s only a credible concern if the—if we make the assumption that people are going to carry on generating the same kind of amount of pollution per person that they do today. Which is of course, complete nonsense if you have already got technologies to replace fossil fuels with solar energy and to replace—you know, agriculture and methane production by cows and so on—with artificial meat that actually tastes good, and and so on. You know, whether—and you know, of course there’s a variety of other technologies that would need to be involved as well, desalination and so on. But you get the idea.MATT: This is incredibly thoughtful here, by Aubrey, and I just wanted to point this out. Too many technologists do not look into the potential implications of what they are working on and what will happen if they are in fact successful. I like here that Aubrey is working with leaders in the space and addressing some of the challenges. If we do live longer, what the hell do we do? We got one planet, we got so many resources and we’re polluting the hell out of it! We need to make sure that we can improve in other ways to be able to accompany either an increased lifespan or an increase—an increased population. And I just wanted to highlight that because you don’t see this happening enough.Yeah, it all—it all runs together. I’ve heard you say previously that the first humans that will live to be a thousand years old have already been born. Can you talk a little bit about the exponential impact of aging—how we slow things down in the flywheel effect?AUBREY: Absolutely. So first of all I never say that it’s certain that the first thousand year old has already been born. I am very well aware that this is pioneering technology and there is plenty of uncertainty about timeframes in any pioneering technology. But I do think it’s very probable—in fact I think it’s quite likely that the first person to live to a thousand is already in their forties or fifties—or, and perhaps even older. So the question is, “Why do I think that?” And a lot of people misunderstand this. Some people think that the reason I’m saying this is because I think that we are within a small number of decades of developing therapies that completely, one hundred percent eliminate aging by repairing every single aspect of the damage that the body accumulates as a side effect of its normal operation. I don’t say that at all. I never have, and I never shall.The actual thing I say is that we will probably never have therapies that are completely, one hundred percent perfect. But we don’t need to have those therapies because what we have is a window of opportunity provided by the—whether—the body is already set up. Essentially the body is set up to tolerate a certain amount of its own self-inflicted damage without significant physiological impact in terms of physical and mental performance, and therefore without substantial risk of death. And all we need to do, therefore, is to keep the overall load of damage—the amount of damage we’re carrying around—below that point. And we can do that incrementally. What we can do is we can develop first generation therapies that remove most of the damage that someone aged—let’s say, sixty or seventy—has accumulated. And then we’ve bought ourselves time—you know, let’s say twenty or thirty years—before the level of damage becomes that kind of level again. At that point, the damage, of course, is more difficult to repair by definition because of the damage that’s going to have accumulated—the damage that the therapies didn’t work on—but that’s an awfully long time to develop better therapies that do repair some of the damage that we couldn’t repair initially in the first generation. MATT: For a simpler metaphor, imagine Tetris. Every time you’re clearing out additional levels, you have that much more time until you run out of the game. We’re playing Tetris with your life and we’re trying to extend it. Here’s how.AUBREY: And of course we can apply those second generation therapies to the same people that the first generation therapies were applied to. So all we need to do is keep one step ahead of the problem and keep improving the therapies fast enough to—to be able to keep the overall damage load lower. And the term that I’ve coined for this—“Longevity Escape Velocity”—I define as simply, “that minimum rate of progress in improving the comprehensiveness.” Now a very important thing to point out here is it’s not quite like you know, the flywheel effect of the singularity where you need accelerating change. You don’t actually need accelerating change here. In fact, you can get away with having a modest deceleration of the rate of progress, you know, and still you stay one step ahead of the problem. Because if you think about it, the time you have for the next step is dependent on how much—on how rapidly things still accumulate and that goes down as fewer things accumulate.MATT: Exactly, it’s—it’s prevention versus intervention. If you can add a year of healthy life for every year someone lives, eventually you reach close to that escape velocity, or that thousand year time horizon. What are—what are the cutting edges right now in terms of prevention, what you guys are looking at? And then comment on the Silicon Valley Blood Boys.AUBREY: Well, well well as I say we have a very much a “divide and conquer” strategy—lots of things at the same time. Most longstanding and major project in our own research laboratory is on mitochondrial mutations which accumulate throughout life and they appear to have very diverse and widespread effects on aging. People really have, you know, pretty much given up on doing anything about them in terms of actually eliminating them. But an idea that was put forward more than thirty years ago—it has much more legs—the idea was and is to, to essentially put back-up copies of the mitochondrial genes into our normal nuclear chromosomal DNA and modify it in such a way that they still work, even though the DNA is in the wrong place. That sounds like it would be really hard but it’s actually—there are reasons to believe that it might not be not so hard at all. But it turns out it isn’t easy either and that’s why people gave up. But we’ve made some very important breakthroughs over the past several years that have allowed us to get to a point where it very much looks within reach. And it’s now a very active and live field again. Outside of our own lab we have a number of projects still going extramurally—one very important one is the elimination of cross-linking in the extracellular matrix. So this lattice of proteins—the extracellular matrix that gives our tissues their biophysical properties, their elasticity and so on—chemical changes happen to that extracellular matrix and they accumulate because the ECM is not significantly turned over and recycled during life so we are working to reverse that. And again we have made great breakthroughs in that area—including very high profile publications—and that’s now turning into, you know, a project that can be spun out. It’s actually going to be our next spin out in the next few months. Ones that we’ve already spun out are related to molecular waste products—like for example, the derivative of Vitamin A that accumulates in the back of the eye and is the ultimate cause of macular degeneration, which I’m sure you know is the number one cause of blindness in the elderly. That’s a problem that we—we’ve started to work on maybe ten years or more ago. And we’ve identified ways to deal with that problem by—by inserting genes encoding bacterial enzymes that can break down this nasty toxin. And it turns out that there’s been some success now, in getting those modified versions of that bacterial gene to actually work and that will going—that’s now a company out in upstate New York near Syracuse named ICHOR: I-C-H-O-R. And it’s planning to go into clinical trials within the next year.MATT: How do you balance out long-term and short-term time horizons? So to be able to have the most impact, you guys need to be funded; you need to be able to prove results; and be moving as quickly as possible. Yet some things just take time!AUBREY: Well that’s for sure. And certainly, you know, I’ve always looked at a financial support challenge as a near-term challenge. Because every incremental step that we make improves the credibility of the overall exercise, as well as of course, the credibility of our team. And therefore makes it that much easier to get the next aliquot of money in the door. And that certainly is the way it’s been going. For a long time it was hell-on-wheels to get any money to speak of. But the fact that we’ve been able to get projects—several projects now, as I mentioned—up to the point of being spun out, has allowed us to attract significantly more money. And for sure, the momentum is there. But it’s just a matter of still putting in all the effort we possibly can to make that happen. One of our biggest challenges right now is that many of the people who have deep pockets and who basically do get and support what we do—they are fundamentally investors first, and philanthropists second. And yes they will, you know, be much more interested in supporting something once it has been spun out. But there are inevitably going to be other projects—like the mitochondrial one I mentioned, that simply hasn’t quite reached the point of being a value proposition, even a high-risk high-reward one—and therefore we need these people also to be philanthropic. Now luckily we have been able, in most cases, to make the case to such investors that it’s in their investment interest, not just their humanitarian interest to—to donate as well as invest. Simply because by donating significant amounts, they get access to us—they can come visit us any time and you know, talk to the scientists and generally be at the cutting edge of the progress of knowledge. Which means that they’re in a position to be the first mover and the lead investor at the stage where subject project does get to the spinning out stage. And we’ve been able to sell that argument fairly effectively. So yeah, I think they’re getting better.MATT: And they get to live longer. So obviously they probably have slightly early access.AUBREY: You get to live longer. It’s all a game of probabilities here so they—we don’t, we don’t—we can’t tell them that they’ll definitely live longer or that they’ll be first in the queue for the treatment when those treatments get to the clinic. But we don’t need to tell them that if we can tell them that they have a chance of making money.MATT: And pasta definitely can’t hurt. So you’re a pretty—you’re a pretty skinny guy, Aubrey. So the most successful life extension to date has more or less been revolving around calorie restriction and intermittent fasting. What can people do if they want to maximize their longevity and what can we expect reasonably?AUBREY: Yeah, so I have to give a bit of a nuanced answer here. Yes you’re right, I am thin. And indeed I am doing very well for my age—I always come out very biologically young whenever I get tested.MATT: How old are you?AUBREY: Fifty-five.MATT: Okay.AUBREY: But that’s not necessarily good news for the idea that calorie restriction is the thing to do. I—indeed, I don’t eat much, I guess. And somehow or other I can eat and drink exactly what I like and I—I don’t even need too much exercise and I seem to be doing very well on it. But for somebody who—for an average person, the evidence that calorie restriction can significantly increase lifespan is basically null. It may actually have a most effect on keeping you healthy and resilient against infections and so on; and maybe very slightly increase your life by a year or two if you’re lucky. But it certainly—certainly the evidence is pretty conclusive that we will not be able to increase life by the kind of proportion that we see in the laboratory, with mice or rats, like the thirty or forty or fifty percent proportions that we see. And it’s very important to—for people to know that. Not—I’m not telling people not to do, so yeah, absolutely—I’m not saying that at all. So yeah, it’s good for you. And the drugs that are coming along these days that may be able to trick the body into thinking it’s on a famine when it’s not—like rapamycin—such like, you know, again for the same reason those drugs may be beneficial. But one absolutely has to have a good sense of proportion with regard to how beneficial. Because if you think they are the Holy Grail and they’re going to give you everything you need, then that’s going to correspondingly diminish you interest and enthusiasm for helping the research that we’re doing now to develop stuff that doesn’t yet exist. I firmly believe that, you know, we need much more understanding of what the—what the—what the-the-the-the-the-the disparity is between what we can do today and what we have a good chance of being able to do in the future, in order to motivate people to bring that future closer.MATT: How do you balance that? Because you are essentially researching—or seeking—the Fountain Of Youth, so to speak. There’s a lot of ways that it could go wrong, or people could think certain things. Do you have to take any special precautions to not set unrealistic expectations?AUBREY: I have the opposite problem. People already have unrealistically pessimistic expectations. Now a number of my colleagues who work in the biology of aging feel that that’s the way it ought to be. That you know, it’s better to err on the side of caution. And of course up to a point that’s true. But it goes far too far in our particular case because since the entire—since the dawn of civilization people have wanted desperately to have this “Fountain Of Youth”. And it hasn’t happened. And so you know, there is a very strong tendency to be so pessimistic about the foreseeability of any kind of medical control of aging that you put it out of your mind, as I mentioned earlier on. And as you’re putting it out of your mind you’re pretending that it’s impossible. Of course you’re not going to be particularly interested in government money, for example, being spent on it. In fact you’d probably think it was a bad thing for the government to do. And therefore there’s no votes in putting money into this vital research area—the single, most important problem for humanity as I said earlier—which is very bad. So I believe that far from being irresponsible in going out and giving predictions about time frames and so on—as I do, which my colleagues say that I am—I think it’s they who are irresponsible for-for-for-for-for not doing that, for refusing to go out and say what they think is actually likely to happen and how soon; because people are making up their own answers to that question and those answers are unrealistically over-pessimistic.MATT: Every movement requires a charismatic salesman to get out there and make that dream a reality—Steve Jobs, Elon Musk—both of them have created incredible empires and they had to be the face. They had to get out there, get public support, and build it up. I like that Aubrey here is doing this, and bringing this up, because as you are trying to create a better world it is incredibly important to both build interest on things that actually do matter. If there’s not enough public support then we stick with sports, short-term mindsets, and things that do not matter. Hence why we’re having Aubrey on——And because of it will kill them earlier; because they’re living their life in that way.AUBREY: Well it’s partly because they will live their life in a way that doesn’t extend—that doesn’t maximize that potential. But it’s worse than that. The main thing is they are living their life in a way that is not maximizing the speed at which we develop new therapies. So in other words they’re not maximizing their own probability of making the cut—but in both directions. They’re not maximizing their own life, and they’re also not minimizing the time before things come along that can change that maximum.MATT: So we talked about this a little bit before. But a big part of Fringe FM, in addition to shifting humanity’s focus—humanity is so short-term-incentive-focused; we love instant gratification which is why a lot of people have trouble with what you guys are focused on—part of it is shifting to a “further out” time frame, because we’re able to accomplish much more when we have longer time horizons. And part of it’s also getting incredible people like you to see what else you’re interested in. You talked about it a little bit more—but what are what are some cutting edge sciences—or businesses, etcetera—that you’re most plugged into and you would like to see on the program?AUBREY: Well “plugged into” is probably an exaggeration because as you have said I’m a busy guy. And you know, I don’t have enough time to really get in-depth knowledge of other fields. I’m—I’m only recreational, really. But really, you name it you know—everything that is pioneering and potentially transformative is the kind of thing you ought to have on the show. Whether it’s renewable energy; or artificial meat; or desalination; or artificial intelligence for automation; or you know, space travel—all of these things can profoundly change, the you know; the-the-the-the human condition, the-the-the quality of life that people have and of course, in some cases, the quantity of life. But as I say that is a side effect of quality. MATT: And quality—quality’s the most important.AUBREY: Well I don’t—okay, so so let me actually stop you there. Because it’s very important not to be telling people, “Oh quality is more important than quantity”. The reason it’s important not to do that is because today people think of quality and quantity as in some case—some sense you know, opposed to each other. There’s a trade-off there. And of course there is a trade-off today because there are plenty of things that we like to do that are bad for us—whether it’s smoking or going to McDonald’s or whatever, right? But in a future in which we have medicines that can keep us healthy, it’s exactly the opposite—quality confers quantity. And therefore trying to say—“Oh quality is a good thing because you don’t have to worry about this kind of ambiguous quantity thing”—you know that’s kind of misrepresenting the situation. It’s misrepresenting it in a counterproductive way because people will then say—“Okay, we should be working on modest goals”—you know, trying alleviate or postpone by a few years this-or-that age-related disease. And that’s absolutely crazy. It misleads people. It gets people into a—into you know, spending money on the wrong research, to be perfectly honest. We need to be less scared than we currently are of that side effect; that “quantity” side effect of the quality improvement. MATT: No, you’re very true. I was thinking more of a derivative in terms of area under the, the quality-time horizon. I’m—I know—I know you’re very busy and have a, have a bunch of other things you need to get to. I have two last questions for you: So when would you say—let’s say I have a son now. Realistically speaking what would you put the odds at of him living to be greater than a hundred and fifty? Eighty percent—okay, what makes you so confident? Ninety—okay, I’m of a similar mindset especially considering all of the technologies that are slowly starting to merge into extending the effectiveness of your field, so to speak. And my—my last question for you would be: what do you need the most help with, or if you had unlimited funding, what would you focus on?AUBREY: Those are two different questions. Because the thing I need the most help with is funding. So, I mean—and this has been true for a very long time. When I started out in this field—twenty odd years ago—I had three problems to solve: I had to figure out how to defeat aging; I had to figure out how to bring the experts together who were the world leaders that were most equipped to implement my plan to defeat aging; and then I had to find the money to let them get on and do the job. And you know, I was rather gratified that, after only five years in the field, I came up with a fundamental plan. You know, I got a new concept—the concept of comprehensive damage repair—that has stood the test of time! You know, it’s something that I immediately saw with a radical departure and was much more likely to succeed. And it turns out I seemed to be right. So that was great.In terms of bringing the people on board, that also turned out to be a rather easy problem to solve. And in fact, you know, I would say certainly by the early 2000s I had basically done that. All of—by no means, all of the scientific community agreed that what I was saying was true. But I didn’t need all the scientific community to say that. I only needed the right people and that turned out to be an easy thing to actually achieve. So for more than a decade now, the only one of those three problems that has remained is the problem—is the last one, that’s actually giving these people the wherewithal to get on, get on and do this stuff. And you know it is, as I say, things are looking up these days. But we still—I mean I still—spend far more of my time, one way or another, trying to fundraise than I do even, you know, talking to my my colleagues in the scientific community which is pretty sad, really. Then to answer the second question: what would I do—what would I be doing if I had infinite money—well, basically the same as what we’re doing now, it’s just, you know, with with more people. Huge amounts of what we do could be going faster if they were just more parallelized—you know, if they just had more manpower. There’s obviously obviously diminishing returns in that. They come to a point where you know, where the the limiting factor is simply the difficulty of the science; but we’re probably an order of magnitude away from that right now. I think that if we just had one more digit on our current budget—which I couldn’t believe five million dollars per year—one more digit on that would be going be going three times faster. Now as I mentioned earlier, the—every step we take improves our credibility; improves the overall credibility of the gaol and therefore makes it easier to get the next aliquot of money. So I think, you know, that’s—that problem is going to go away over time. But it definitely hasn’t gone away yet.MATT: Is it frustrating to see how easily blockchain projects are raising money with ICOs?AUBREY: Well I’m actually not frustrated by that for two reasons: First of all, there are ICOs being developed around longevity right now. So maybe that will work out, and maybe the enthusiasm for ICOs will feed in our direction. But also rather more concretely, six months ago we—around Christmas—we had a number of very welcome new and large new donations which have put us into a much healthier financial state than we were. And all four of those donations came from people who have made a large amount of money out of blockchain—out of the explosion in cryptocurrencies. So yeah, and my my view of the whole crypto-pipe is-is-is-is-is not quite so negative as you might think.MATT: And it’s perfect that you have—if you have a non-profit, you guys can take money, they can get some money off the tax books, and they can try to extend their life in that in the future.I—I know, let’s wrap this thing up. What would you like to leave listeners with—a challenge, a statement, something you’d like them to look into?AUBREY: Let’s go with a challenge. The challenge is: find a way to help. A lot of people, when they hear about what I have to say, they say, “Yeah I like that idea, that’s very important—but I’m not equipped to make a difference in this area, you know; I’m not a scientist, I’m not a billionaire, you know, what can I do?” That’s bullshit. It’s complete bullshit. First of all, there are people who have their own podcasts, you know? Who can, perfectly-well give greater exposure to this kind of thing. And obviously, I’m very grateful to you for-for-for playing that role. But beyond that, since the money is the number one problem—why such a distance—all aspects of advocacy are important. People say—“Well I don’t have much money, I can’t give much money”—I always point out that the less money you have, the more people you know who have more money than you! In other words, the greater your relevant audience is for advocacy! So absolutely get the hell out there! You know, know your stuff—understand the science and its fundamentals—you don’t need to understand the details, just understand the fundamentals so that you can give good answers to every question. You know, and understand obviously also of the right answers to the concerns people have—whether it’s overpopulation, or paying the pensions, or whatever—because these answers are there! I’ve been giving the same bloody answers to the same, you know—over and over again, week in, week out for decade you know. Learn that, get out there, and use it! Change people’s mind! You don’t even have to change people’s mind completely. You know, if you meet someone who’s vigorously opposed to this and you can just make them a little less sure—then they will be a little less vocal in dissuading other people to board this! And that’s good enough. I know a number of billionaires who really, really support this. And who really want to give us money. And the reason they don’t is because their wives don’t want them to. I am not kidding! So advocacy matters at every level—whether you’re moving someone an inch away from committed opposition to less committed opposition, or whether you’re moving someone from committed support to support that’s committed enough to actually write a check it doesn’t matter. Anywhere on that spectrum—if you move people in the right direction, it’s worth it! So get out there and be an advocate. MATT: Absolutely. Get out there and be an advocate. Donate to the causes you support and if you do, you get to avoid a little bit of those tax dollars which are absolutely terrible. So check him out, guys. Where’s the best place?AUBREY: Best place to go is of course, our website: sens.org—“s” for sugar, “e” for elephant, “n” for November, “s” for sugar, dot “o-r-g”. We have a nice, friendly “donate” button. And if you happen to be in a position to write a large check, it’s pretty easy to see how to contact us and arrange that too.MATT: So what’s up with the beard, Aubrey? That’s the last one.AUBREY: I grew this beard because my ex-wife campaigned for it for a long time. And hey, it’s no problem! It’s low maintenance. I guess I don’t even have to do anything special to maintain it.MATT: And now you have the brand image of being Gandalf! It’s very powerful. Thanks—thanks for coming on!AUBREY: Thank you very much, Matt.“AUBREY DE GREY: Well I do think it’s very probable. In fact, I think it’s quite likely that the first person to live to a thousand is already in their forties or fifties—or, and perhaps even older. So the question is, “Why do I think that?” And a lot of people misunderstand this. Some people think that the reason I’m saying this is because I think that we are within a small number of decades of developing therapies that completely, one hundred percent eliminate aging by repairing every single aspect of the damage that the body accumulates as a side effect of its normal operation. I don’t say that at all. I never have, and I never shall. MATT: Survival of the fittest—Darwin realized evolution is merely the process of survival. Nothing has been more driving a force as survival. Nothing wants to die. I don’t want to die. You don’t want to die—even if you’ve accepted death. When there’s a way around it, we would give anything. Today we’ve got Aubrey de Grey. Aubrey’s the Cambridge researcher and chief science officer of the SENS Research Foundation. They’re focused on aging and extending human longevity. He thinks that today humans are alive who’ll live to be a thousand years old. The first have already been born. Is it you? Is it me? Find out. Aubrey is the chief editor of the academic journal, “Rejuvenation Research”. He’s the author of “The Mitochondrial Free-Radical Theory of Aging” and the co-author of “Ending Aging”. He’s given some incredibly successful TED Talks and has been interviewed on most major news sources including: “CBS”, “60 Minutes”, “The BBC”, “The New York Times”, “Fortune”, “The Washington Post”, “TED”, “Popular Science”, “The Colbert Report”, and “The Skeptic’s Guide to the Universe”. he’s been everywhere and more. And makes sense! His non-profit is focused on extending quality human life and helping us all live longer. And he thinks—you know what? We can do it. This is an incredibly interesting interview—something I, personally am very passionate about and I would say all of us are. If we can get extra years on our life, especially good quality years, we would give—well, anything—as long as you don’t die, right? Today we discuss why Aubrey switched from studying artificial intelligence to the science of human longevity; the causes of aging and how we can cure them; why prevention is orders of magnitude more effective than intervention; the reason Aubrey thinks that we will, in fact, live to a thousand; why there isn’t enough funding or support, currently, for fighting aging; the reason stem cell research is progressing rapidly and proving very fruitful; how caloric restriction affects metabolism and aging; why SENS often spins out businesses to further their aims; the true science of immortality; and how mainstream media has reacted to the prospect of increased life-span. And now, without further ado, I give you Aubrey de Grey. So Aubrey, when did you first become obsessed with aging?AUBREY DE GREY: So yeah, it wasn’t when I was young, actually. Because when I was young I was laboring under a fabulously tragic misconception. And the misconception was that everybody realized that aging was the world’s most important problem—and the problem that could potentially be solved by a medicine of the future, and we should be kind of working to make that happen as soon as possible. This was completely obvious to me from my earliest days. And I just never did the experiment of actually asking people, you know, whether they agreed with me. The idea that they wouldn’t was like the idea that they wouldn’t think the sky was blue. So it was actually not until my late twenties that I started thinking about this. I had, by that time, forged a pretty successful career for myself in artificial intelligence research. And I was perfectly happy doing that. And then I had—when I was twenty-six I met, and shortly afterwards married a biologist who was a lot older than me. She was a senior professor already. And through her not only did I learn a lot of biology—I also discovered, you know, gradually began to realize—that we were never talking about aging. And I started asking questions and it turned out that she wasn’t actually very interested in aging. She thought it wasn’t very important. And it wasn’t just her, it was all the other biologists I was meeting. So, you know, it was a complete revelation to me—and a very tragic one—to discover that actually, no, almost everybody in the world was mad and was taking the view that aging is something we should make our peace with. And so eventually after a couple more years of coming to terms with that I decided I had to switch fields. And here I am.MATT: And it’s the problem of, when you’re getting attacked, don’t ask someone for help—don’t ask everyone for help, ask someone for help. Is the tragedy of a common scenario, or is it just something that people thought was quite literally impossible? AUBREY: I think it’s a multi-layered thing, actually. Certainly, I believe that almost everybody had convinced themselves—and indeed, of course, still today, we haven’t by any means completely solved this problem—had convinced themselves that aging is absolutely inevitable. But the medical control of aging, of the same—on the same scale that we can medically control most infections with something it can to create into perpetual motion. Well on top of that, people had also convinced themselves—and again, this is a problem that still exists in a big way—that aging was some kind of blessing in disguise. You know, that there was some kind of, you know, huge amount of tragedy that would occur if we, by some miracle, did actually eliminate aging, that it probably would create as a result, would be even worse. And all of this has, of course, been built up over the history of civilization, and I believe that it’s been built up as a result of our knowledge that aging is this absolutely ghastly thing—and our psychological need to put it out of our minds. And even today, when obviously medicine and medical research is advancing so rapidly, people are still—you know, with some justification—very hesitant to get their hopes up. And you know, it’s all very well getting your hopes up, if “you don’t mind your hopes being dashed because at least you tried” kind of thing. Which is my attitude—but of course, a lot of people take the view that having one’s hopes dashed is really not much fun and therefore they’d prefer not to get them up in the first place. And that is a huge part of the problem that we face today.MATT: That’s the eighty-twenty scenario: twenty percent of people will take action; eighty percent will just sit by and hope. So you’re you’re taking action now—talk to me a little bit more about SRF—what you guys are focusing on, and what the cutting-edge is when it comes to human longevity?AUBREY: Sure. Well I mean, first of all, let me actually come back on what you just said. If twenty percent of the population actually were getting up and doing things, then my job would be done. If twenty percent of a percent were doing so, my job would be done. Unfortunately we have to rely on a very very small minority of people who are pushing this forward.MATT: Hey Matt here. This the purpose of Fringe FM: To get on the point-zero-one percent of people that are transforming the world—transforming society in our collective future. To highlight them, and to try to inspire others like them—to get in on the game and to try to help us improve our collective future. If this sounds interesting for you I recommend reaching out to Aubrey. Or if you’re focused on other things entirely, just put in the effort. Now let’s jump back. AUBREY: And SENS Research Foundation—which is the 501(c)(3) public charity that I helped to create a decade or so ago—is still leading the way in this area. We absolutely pioneered the whole field of research on what we like to call “comprehensive damage repair” as an approach to medically controlling aging—which essentially consists of a divide and conquer approach of identifying a manageable, but still, you know, a non-trivial number of of types of damage that the body does to itself throughout life—and figuring out and developing ways to to repair that damage, so as to put the molecular and cellular structure of the body back into a state resembling how it was at an earlier age. And so we continue to have a variety of different projects. Some of them we pursue internally at our research center in Mountain View, California. A lot of them we pursue extramurally, so to speak—in other words we support laboratories and internships in universities that addressing some of these problems. And what I am very happy to be able to say is that over the past few years we have augmented all of that with the private sector. In other words, we have been able to take a succession of projects, so far, five—to a point of sufficient group of concept—that we’ve been able to spin them out. We’ve been able to get investors interested. Obviously, not any old investor. It really is very much the more visionary, “high-risk, high reward” types, the angles. But yeah, getting investors interested enough that it’s been possible to create companies and get people involved who are you know, I guess not fond of giving money away and whose whose whose pockets were not actually being emptied in our favor as a non-profit but who are willing to get involved even in a very speculative, actual investment.MATT: Yeah you’d pay anything to have an extra day—and extra year, on your life. So I imagine you’re doing very very well, especially with Silicon Valley today. You talked about the different types of damage that comes to both body, and I imagine, mind. Can you break down a little bit more what aging actually looks like on on your perspective?AUBREY: Body and mind, certainly. Or perhaps, more accurately, body and brain. You know, and that’s important to say because it’s important to know that the brain is made of more or less the same stuff as the rest of the body. And therefore, the same basic idea—it’s the same conceptual technologies—can be applied to the brain as, in the rest of the body. We certainly don’t want to end up in a state where we have rejuvenated the body really well but we have not rejuvenated the brain. But there is no real danger of that happening because the same technologies—the same ideas—can be applied. So what are these types of damage? Well, normally we divide the damage into seven major categories. We talk about things like cell loss. In other words, cells dying and not being spontaneously replaced as they die, by the division of other cells. This is a very generic idea of course. But it’s a concrete idea, it’s not just a theoretical, abstract thing. It really does happen in a variety of different tissues. And it happens progressively during life. So of course, eventually one ends up with an affected tissue and not having enough cells to do its job. And we all know what we can do to fix this. We simply inject stem cells, which are prepared in a laboratory into the right kind of state. So that they know what to do, to divide and transform themselves—differentiate, as we say—into replacements for the cells that the body is not replacing at the time. Simple idea, of course much easier said than done and that’s why there’s so many researchers out there doing stem cell therapy. But, of course the other reason why there are so many people out there doing stem cell research is that it is an established field. It’s something that people get. And therefore, they’re willing to put money into it. Whether it’s public money or private money. The reason why SEMS Research Foundation exists is because most of the other categories are not so fortunate. They are much less well-understood and appreciated—in particular, the type of damage may be appreciated but the approaches to repairing the damage may not be—and therefore we’ve had to step into that bridge and cross that “valley of death” and put, you know, work into developing at least the early stages of therapies that repair the other type of damage.MATT: How much is your work held back by religious values and politics?AUBREY: Well, okay, let’s do those two questions separately—religious values, one, and then politics. So religious values, very little—it may, that may change, you know—it may be that as this begins to really grow and become, you know, become a big deal in society overall; much less the problem but the solution; that there is more debate in this area. But so far what’s happened is that insofar as religious people start to think about this and start to be concerned that this is even somewhere, you know diverting God’s plan or whatever—that it’s actually rather easy to change their minds. My standard approach is to say: “Well look here—the idea here is not to extend life—the idea is to extend healthy life. And of course we know, and we do not want to shy away from the fact that extending a healthy life will have a side effect of extending life on average—but, all that means is number one: we are alleviating suffering. You know, we are doing exactly what the Holy Scripture—whether it’s the Bible, or the Quran, or whatever—tells you to do. We are actually improving people’s quality of life which seems to be the right thing to do. So you can certainly argue that it would be a sin not to be working on this. Secondly—you know, insofar as this could be considered to be disrupting God’s plan—well you know, last time I looked God was supposed to be omnipotent, right? So you know, He can perfectly well strike you down with a thunderbolt however healthy you are. So you know, it’s very hard to make an argument that we’re in any way usurping God in this. MATT: What about with stem cell research? I know that’s not mainly your topic.AUBREY: No no no, great example! I mean, stem cell—we don’t do stem cell research very much. But the only reason we don’t do it is because other people are doing things that are needed. So we very much regard stem cells as an indispensable component of this. But what you have to remember is that religious groups were never against stem cell research or stem cell therapy, per se, at all. The only thing they were against were the use of stem cells that were derived in a particular manner that involved destroying embryos. Now today that’s basically completely irrelevant, and completely side-stepped because we have this thing called IPS: Induced Pluripotency where you can take a cell that isn’t a stem cell at all and you create cells that are almost exactly the same in terms of their behavior, as the cells that were being got from embryos—without any embryos being involved. So the whole ethical issue that underpinned the politics around stem cells and over a century, you know—has completely gone away.MATT: When when did that come around? And how how close are you working with people in related fields—say, say clean meat manufacturing, synthetic biology, etcetera—that are focused not on extending life but on similar, similar systems? AUBREY: So first of all, wind it up yes come along it was really kick-started by one paper that was published by a Japanese group, the group Shinya Yamanaka in 2006 and it exploded. It was like—it turned out that the techniques that Yamanaka had very painstakingly identified and developed were very easy to replicate in other labs. Very often that’s not true—you get a breakthrough that would actually take a long time for people to figure out the intricate details of how to get it to work in their own hands. But that wasn’t the case for this. So yeah, IPS is—is you know, really really game-changing and it’s been around for more than a decade now. Sorry, what was your other question again?MATT: The other question was how close are you in working with other people that are working in related fields, say clean meat?AUBREY: So the second answer is we’re not really working closely with them. We don’t have formal links with people working in, for example, artificial meat. But, I do certainly pay strong attention to those groups. And also, for that matter, to groups not necessarily working in biotech per se—but in other transformative technology like artificial intelligence and renewable energy and so on. And the largest part of the reason I pay attention is not just recreationally because it’s a personal interest; but because the progress that is made by those groups in those areas will actually play a big role in ensuring that when we do bring aging under medical control we will not create new problems that are really difficult to address. So for example let’s just take overpopulation. People say, “Oh dear, where do we put all the people” you know—we’ve got this problem of climate change and so on today, you know because of too many people; you know it’s going to get worse if people are not dying anymore. And of course that’s only a credible concern if the—if we make the assumption that people are going to carry on generating the same kind of amount of pollution per person that they do today. Which is of course, complete nonsense if you have already got technologies to replace fossil fuels with solar energy and to replace—you know, agriculture and methane production by cows and so on—with artificial meat that actually tastes good, and and so on. You know, whether—and you know, of course there’s a variety of other technologies that would need to be involved as well, desalination and so on. But you get the idea.MATT: This is incredibly thoughtful here, by Aubrey, and I just wanted to point this out. Too many technologists do not look into the potential implications of what they are working on and what will happen if they are in fact successful. I like here that Aubrey is working with leaders in the space and addressing some of the challenges. If we do live longer, what the hell do we do? We got one planet, we got so many resources and we’re polluting the hell out of it! We need to make sure that we can improve in other ways to be able to accompany either an increased lifespan or an increase—an increased population. And I just wanted to highlight that because you don’t see this happening enough.Yeah, it all—it all runs together. I’ve heard you say previously that the first humans that will live to be a thousand years old have already been born. Can you talk a little bit about the exponential impact of aging—how we slow things down in the flywheel effect?AUBREY: Absolutely. So first of all I never say that it’s certain that the first thousand year old has already been born. I am very well aware that this is pioneering technology and there is plenty of uncertainty about timeframes in any pioneering technology. But I do think it’s very probable—in fact I think it’s quite likely that the first person to live to a thousand is already in their forties or fifties—or, and perhaps even older. So the question is, “Why do I think that?” And a lot of people misunderstand this. Some people think that the reason I’m saying this is because I think that we are within a small number of decades of developing therapies that completely, one hundred percent eliminate aging by repairing every single aspect of the damage that the body accumulates as a side effect of its normal operation. I don’t say that at all. I never have, and I never shall.The actual thing I say is that we will probably never have therapies that are completely, one hundred percent perfect. But we don’t need to have those therapies because what we have is a window of opportunity provided by the—whether—the body is already set up. Essentially the body is set up to tolerate a certain amount of its own self-inflicted damage without significant physiological impact in terms of physical and mental performance, and therefore without substantial risk of death. And all we need to do, therefore, is to keep the overall load of damage—the amount of damage we’re carrying around—below that point. And we can do that incrementally. What we can do is we can develop first generation therapies that remove most of the damage that someone aged—let’s say, sixty or seventy—has accumulated. And then we’ve bought ourselves time—you know, let’s say twenty or thirty years—before the level of damage becomes that kind of level again. At that point, the damage, of course, is more difficult to repair by definition because of the damage that’s going to have accumulated—the damage that the therapies didn’t work on—but that’s an awfully long time to develop better therapies that do repair some of the damage that we couldn’t repair initially in the first generation. MATT: For a simpler metaphor, imagine Tetris. Every time you’re clearing out additional levels, you have that much more time until you run out of the game. We’re playing Tetris with your life and we’re trying to extend it. Here’s how.AUBREY: And of course we can apply those second generation therapies to the same people that the first generation therapies were applied to. So all we need to do is keep one step ahead of the problem and keep improving the therapies fast enough to—to be able to keep the overall damage load lower. And the term that I’ve coined for this—“Longevity Escape Velocity”—I define as simply, “that minimum rate of progress in improving the comprehensiveness.” Now a very important thing to point out here is it’s not quite like you know, the flywheel effect of the singularity where you need accelerating change. You don’t actually need accelerating change here. In fact, you can get away with having a modest deceleration of the rate of progress, you know, and still you stay one step ahead of the problem. Because if you think about it, the time you have for the next step is dependent on how much—on how rapidly things still accumulate and that goes down as fewer things accumulate.MATT: Exactly, it’s—it’s prevention versus intervention. If you can add a year of healthy life for every year someone lives, eventually you reach close to that escape velocity, or that thousand year time horizon. What are—what are the cutting edges right now in terms of prevention, what you guys are looking at? And then comment on the Silicon Valley Blood Boys.AUBREY: Well, well well as I say we have a very much a “divide and conquer” strategy—lots of things at the same time. Most longstanding and major project in our own research laboratory is on mitochondrial mutations which accumulate throughout life and they appear to have very diverse and widespread effects on aging. People really have, you know, pretty much given up on doing anything about them in terms of actually eliminating them. But an idea that was put forward more than thirty years ago—it has much more legs—the idea was and is to, to essentially put back-up copies of the mitochondrial genes into our normal nuclear chromosomal DNA and modify it in such a way that they still work, even though the DNA is in the wrong place. That sounds like it would be really hard but it’s actually—there are reasons to believe that it might not be not so hard at all. But it turns out it isn’t easy either and that’s why people gave up. But we’ve made some very important breakthroughs over the past several years that have allowed us to get to a point where it very much looks within reach. And it’s now a very active and live field again. Outside of our own lab we have a number of projects still going extramurally—one very important one is the elimination of cross-linking in the extracellular matrix. So this lattice of proteins—the extracellular matrix that gives our tissues their biophysical properties, their elasticity and so on—chemical changes happen to that extracellular matrix and they accumulate because the ECM is not significantly turned over and recycled during life so we are working to reverse that. And again we have made great breakthroughs in that area—including very high profile publications—and that’s now turning into, you know, a project that can be spun out. It’s actually going to be our next spin out in the next few months. Ones that we’ve already spun out are related to molecular waste products—like for example, the derivative of Vitamin A that accumulates in the back of the eye and is the ultimate cause of macular degeneration, which I’m sure you know is the number one cause of blindness in the elderly. That’s a problem that we—we’ve started to work on maybe ten years or more ago. And we’ve identified ways to deal with that problem by—by inserting genes encoding bacterial enzymes that can break down this nasty toxin. And it turns out that there’s been some success now, in getting those modified versions of that bacterial gene to actually work and that will going—that’s now a company out in upstate New York near Syracuse named ICHOR: I-C-H-O-R. And it’s planning to go into clinical trials within the next year.MATT: How do you balance out long-term and short-term time horizons? So to be able to have the most impact, you guys need to be funded; you need to be able to prove results; and be moving as quickly as possible. Yet some things just take time!AUBREY: Well that’s for sure. And certainly, you know, I’ve always looked at a financial support challenge as a near-term challenge. Because every incremental step that we make improves the credibility of the overall exercise, as well as of course, the credibility of our team. And therefore makes it that much easier to get the next aliquot of money in the door. And that certainly is the way it’s been going. For a long time it was hell-on-wheels to get any money to speak of. But the fact that we’ve been able to get projects—several projects now, as I mentioned—up to the point of being spun out, has allowed us to attract significantly more money. And for sure, the momentum is there. But it’s just a matter of still putting in all the effort we possibly can to make that happen. One of our biggest challenges right now is that many of the people who have deep pockets and who basically do get and support what we do—they are fundamentally investors first, and philanthropists second. And yes they will, you know, be much more interested in supporting something once it has been spun out. But there are inevitably going to be other projects—like the mitochondrial one I mentioned, that simply hasn’t quite reached the point of being a value proposition, even a high-risk high-reward one—and therefore we need these people also to be philanthropic. Now luckily we have been able, in most cases, to make the case to such investors that it’s in their investment interest, not just their humanitarian interest to—to donate as well as invest. Simply because by donating significant amounts, they get access to us—they can come visit us any time and you know, talk to the scientists and generally be at the cutting edge of the progress of knowledge. Which means that they’re in a position to be the first mover and the lead investor at the stage where subject project does get to the spinning out stage. And we’ve been able to sell that argument fairly effectively. So yeah, I think they’re getting better.MATT: And they get to live longer. So obviously they probably have slightly early access.AUBREY: You get to live longer. It’s all a game of probabilities here so they—we don’t, we don’t—we can’t tell them that they’ll definitely live longer or that they’ll be first in the queue for the treatment when those treatments get to the clinic. But we don’t need to tell them that if we can tell them that they have a chance of making money.MATT: And pasta definitely can’t hurt. So you’re a pretty—you’re a pretty skinny guy, Aubrey. So the most successful life extension to date has more or less been revolving around calorie restriction and intermittent fasting. What can people do if they want to maximize their longevity and what can we expect reasonably?AUBREY: Yeah, so I have to give a bit of a nuanced answer here. Yes you’re right, I am thin. And indeed I am doing very well for my age—I always come out very biologically young whenever I get tested.MATT: How old are you?AUBREY: Fifty-five.MATT: Okay.AUBREY: But that’s not necessarily good news for the idea that calorie restriction is the thing to do. I—indeed, I don’t eat much, I guess. And somehow or other I can eat and drink exactly what I like and I—I don’t even need too much exercise and I seem to be doing very well on it. But for somebody who—for an average person, the evidence that calorie restriction can significantly increase lifespan is basically null. It may actually have a most effect on keeping you healthy and resilient against infections and so on; and maybe very slightly increase your life by a year or two if you’re lucky. But it certainly—certainly the evidence is pretty conclusive that we will not be able to increase life by the kind of proportion that we see in the laboratory, with mice or rats, like the thirty or forty or fifty percent proportions that we see. And it’s very important to—for people to know that. Not—I’m not telling people not to do, so yeah, absolutely—I’m not saying that at all. So yeah, it’s good for you. And the drugs that are coming along these days that may be able to trick the body into thinking it’s on a famine when it’s not—like rapamycin—such like, you know, again for the same reason those drugs may be beneficial. But one absolutely has to have a good sense of proportion with regard to how beneficial. Because if you think they are the Holy Grail and they’re going to give you everything you need, then that’s going to correspondingly diminish you interest and enthusiasm for helping the research that we’re doing now to develop stuff that doesn’t yet exist. I firmly believe that, you know, we need much more understanding of what the—what the—what the-the-the-the-the-the disparity is between what we can do today and what we have a good chance of being able to do in the future, in order to motivate people to bring that future closer.MATT: How do you balance that? Because you are essentially researching—or seeking—the Fountain Of Youth, so to speak. There’s a lot of ways that it could go wrong, or people could think certain things. Do you have to take any special precautions to not set unrealistic expectations?AUBREY: I have the opposite problem. People already have unrealistically pessimistic expectations. Now a number of my colleagues who work in the biology of aging feel that that’s the way it ought to be. That you know, it’s better to err on the side of caution. And of course up to a point that’s true. But it goes far too far in our particular case because since the entire—since the dawn of civilization people have wanted desperately to have this “Fountain Of Youth”. And it hasn’t happened. And so you know, there is a very strong tendency to be so pessimistic about the foreseeability of any kind of medical control of aging that you put it out of your mind, as I mentioned earlier on. And as you’re putting it out of your mind you’re pretending that it’s impossible. Of course you’re not going to be particularly interested in government money, for example, being spent on it. In fact you’d probably think it was a bad thing for the government to do. And therefore there’s no votes in putting money into this vital research area—the single, most important problem for humanity as I said earlier—which is very bad. So I believe that far from being irresponsible in going out and giving predictions about time frames and so on—as I do, which my colleagues say that I am—I think it’s they who are irresponsible for-for-for-for-for not doing that, for refusing to go out and say what they think is actually likely to happen and how soon; because people are making up their own answers to that question and those answers are unrealistically over-pessimistic.MATT: Every movement requires a charismatic salesman to get out there and make that dream a reality—Steve Jobs, Elon Musk—both of them have created incredible empires and they had to be the face. They had to get out there, get public support, and build it up. I like that Aubrey here is doing this, and bringing this up, because as you are trying to create a better world it is incredibly important to both build interest on things that actually do matter. If there’s not enough public support then we stick with sports, short-term mindsets, and things that do not matter. Hence why we’re having Aubrey on——And because of it will kill them earlier; because they’re living their life in that way.AUBREY: Well it’s partly because they will live their life in a way that doesn’t extend—that doesn’t maximize that potential. But it’s worse than that. The main thing is they are living their life in a way that is not maximizing the speed at which we develop new therapies. So in other words they’re not maximizing their own probability of making the cut—but in both directions. They’re not maximizing their own life, and they’re also not minimizing the time before things come along that can change that maximum.MATT: So we talked about this a little bit before. But a big part of Fringe FM, in addition to shifting humanity’s focus—humanity is so short-term-incentive-focused; we love instant gratification which is why a lot of people have trouble with what you guys are focused on—part of it is shifting to a “further out” time frame, because we’re able to accomplish much more when we have longer time horizons. And part of it’s also getting incredible people like you to see what else you’re interested in. You talked about it a little bit more—but what are what are some cutting edge sciences—or businesses, etcetera—that you’re most plugged into and you would like to see on the program?AUBREY: Well “plugged into” is probably an exaggeration because as you have said I’m a busy guy. And you know, I don’t have enough time to really get in-depth knowledge of other fields. I’m—I’m only recreational, really. But really, you name it you know—everything that is pioneering and potentially transformative is the kind of thing you ought to have on the show. Whether it’s renewable energy; or artificial meat; or desalination; or artificial intelligence for automation; or you know, space travel—all of these things can profoundly change, the you know; the-the-the-the human condition, the-the-the quality of life that people have and of course, in some cases, the quantity of life. But as I say that is a side effect of quality. MATT: And quality—quality’s the most important.AUBREY: Well I don’t—okay, so so let me actually stop you there. Because it’s very important not to be telling people, “Oh quality is more important than quantity”. The reason it’s important not to do that is because today people think of quality and quantity as in some case—some sense you know, opposed to each other. There’s a trade-off there. And of course there is a trade-off today because there are plenty of things that we like to do that are bad for us—whether it’s smoking or going to McDonald’s or whatever, right? But in a future in which we have medicines that can keep us healthy, it’s exactly the opposite—quality confers quantity. And therefore trying to say—“Oh quality is a good thing because you don’t have to worry about this kind of ambiguous quantity thing”—you know that’s kind of misrepresenting the situation. It’s misrepresenting it in a counterproductive way because people will then say—“Okay, we should be working on modest goals”—you know, trying alleviate or postpone by a few years this-or-that age-related disease. And that’s absolutely crazy. It misleads people. It gets people into a—into you know, spending money on the wrong research, to be perfectly honest. We need to be less scared than we currently are of that side effect; that “quantity” side effect of the quality improvement. MATT: No, you’re very true. I was thinking more of a derivative in terms of area under the, the quality-time horizon. I’m—I know—I know you’re very busy and have a, have a bunch of other things you need to get to. I have two last questions for you: So when would you say—let’s say I have a son now. Realistically speaking what would you put the odds at of him living to be greater than a hundred and fifty? Eighty percent—okay, what makes you so confident? Ninety—okay, I’m of a similar mindset especially considering all of the technologies that are slowly starting to merge into extending the effectiveness of your field, so to speak. And my—my last question for you would be: what do you need the most help with, or if you had unlimited funding, what would you focus on?AUBREY: Those are two different questions. Because the thing I need the most help with is funding. So, I mean—and this has been true for a very long time. When I started out in this field—twenty odd years ago—I had three problems to solve: I had to figure out how to defeat aging; I had to figure out how to bring the experts together who were the world leaders that were most equipped to implement my plan to defeat aging; and then I had to find the money to let them get on and do the job. And you know, I was rather gratified that, after only five years in the field, I came up with a fundamental plan. You know, I got a new concept—the concept of comprehensive damage repair—that has stood the test of time! You know, it’s something that I immediately saw with a radical departure and was much more likely to succeed. And it turns out I seemed to be right. So that was great.In terms of bringing the people on board, that also turned out to be a rather easy problem to solve. And in fact, you know, I would say certainly by the early 2000s I had basically done that. All of—by no means, all of the scientific community agreed that what I was saying was true. But I didn’t need all the scientific community to say that. I only needed the right people and that turned out to be an easy thing to actually achieve. So for more than a decade now, the only one of those three problems that has remained is the problem—is the last one, that’s actually giving these people the wherewithal to get on, get on and do this stuff. And you know it is, as I say, things are looking up these days. But we still—I mean I still—spend far more of my time, one way or another, trying to fundraise than I do even, you know, talking to my my colleagues in the scientific community which is pretty sad, really. Then to answer the second question: what would I do—what would I be doing if I had infinite money—well, basically the same as what we’re doing now, it’s just, you know, with with more people. Huge amounts of what we do could be going faster if they were just more parallelized—you know, if they just had more manpower. There’s obviously obviously diminishing returns in that. They come to a point where you know, where the the limiting factor is simply the difficulty of the science; but we’re probably an order of magnitude away from that right now. I think that if we just had one more digit on our current budget—which I couldn’t believe five million dollars per year—one more digit on that would be going be going three times faster. Now as I mentioned earlier, the—every step we take improves our credibility; improves the overall credibility of the gaol and therefore makes it easier to get the next aliquot of money. So I think, you know, that’s—that problem is going to go away over time. But it definitely hasn’t gone away yet.MATT: Is it frustrating to see how easily blockchain projects are raising money with ICOs?AUBREY: Well I’m actually not frustrated by that for two reasons: First of all, there are ICOs being developed around longevity right now. So maybe that will work out, and maybe the enthusiasm for ICOs will feed in our direction. But also rather more concretely, six months ago we—around Christmas—we had a number of very welcome new and large new donations which have put us into a much healthier financial state than we were. And all four of those donations came from people who have made a large amount of money out of blockchain—out of the explosion in cryptocurrencies. So yeah, and my my view of the whole crypto-pipe is-is-is-is-is not quite so negative as you might think.MATT: And it’s perfect that you have—if you have a non-profit, you guys can take money, they can get some money off the tax books, and they can try to extend their life in that in the future.I—I know, let’s wrap this thing up. What would you like to leave listeners with—a challenge, a statement, something you’d like them to look into?AUBREY: Let’s go with a challenge. The challenge is: find a way to help. A lot of people, when they hear about what I have to say, they say, “Yeah I like that idea, that’s very important—but I’m not equipped to make a difference in this area, you know; I’m not a scientist, I’m not a billionaire, you know, what can I do?” That’s bullshit. It’s complete bullshit. First of all, there are people who have their own podcasts, you know? Who can, perfectly-well give greater exposure to this kind of thing. And obviously, I’m very grateful to you for-for-for playing that role. But beyond that, since the money is the number one problem—why such a distance—all aspects of advocacy are important. People say—“Well I don’t have much money, I can’t give much money”—I always point out that the less money you have, the more people you know who have more money than you! In other words, the greater your relevant audience is for advocacy! So absolutely get the hell out there! You know, know your stuff—understand the science and its fundamentals—you don’t need to understand the details, just understand the fundamentals so that you can give good answers to every question. You know, and understand obviously also of the right answers to the concerns people have—whether it’s overpopulation, or paying the pensions, or whatever—because these answers are there! I’ve been giving the same bloody answers to the same, you know—over and over again, week in, week out for decade you know. Learn that, get out there, and use it! Change people’s mind! You don’t even have to change people’s mind completely. You know, if you meet someone who’s vigorously opposed to this and you can just make them a little less sure—then they will be a little less vocal in dissuading other people to board this! And that’s good enough. I know a number of billionaires who really, really support this. And who really want to give us money. And the reason they don’t is because their wives don’t want them to. I am not kidding! So advocacy matters at every level—whether you’re moving someone an inch away from committed opposition to less committed opposition, or whether you’re moving someone from committed support to support that’s committed enough to actually write a check it doesn’t matter. Anywhere on that spectrum—if you move people in the right direction, it’s worth it! So get out there and be an advocate. MATT: Absolutely. Get out there and be an advocate. Donate to the causes you support and if you do, you get to avoid a little bit of those tax dollars which are absolutely terrible. So check him out, guys. Where’s the best place?AUBREY: Best place to go is of course, our website: sens.org—“s” for sugar, “e” for elephant, “n” for November, “s” for sugar, dot “o-r-g”. We have a nice, friendly “donate” button. And if you happen to be in a position to write a large check, it’s pretty easy to see how to contact us and arrange that too.MATT: So what’s up with the beard, Aubrey? That’s the last one.AUBREY: I grew this beard because my ex-wife campaigned for it for a long time. And hey, it’s no problem! It’s low maintenance. I guess I don’t even have to do anything special to maintain it.MATT: And now you have the brand image of being Gandalf! It’s very powerful. Thanks—thanks for coming on!AUBREY: Thank you very much, Matt.”
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Aubrey de Grey (@aubreydegrey) is Cambridge researcher and Chief Science Officer of SENS Research Foundation focused on aging and extending human longevity. He proposes that the first human beings who will live to 1,000 years old have already been born. In addition to his research, Aubrey is editor-in-chief of the academic journal Rejuvenation Research, author of The Mitochondrial Free Radical Theory of Aging (1999) and co-author of Ending Aging (2007). De Grey’s research focuses on whether regenerative medicine can prevent the aging process. He works on the development of what he calls “Strategies for Engineered Negligible Senescence” (SENS), a collection of proposed techniques to rejuvenate the human body and stop aging. To this end, he has identified seven types of molecular and cellular damage caused by essential metabolic processes. SENS is a proposed panel of therapies designed to repair this damage. He has been interviewed by most major news sources, including CBS 60 Minutes, the BBC, The New York Times, Fortune Magazine, The Washington Post, TED, Popular Science, The Colbert Report, Time and the Skeptics’ Guide to the Universe. [spreaker type=player resource=”episode_id=18590674″ width=”100%” height=”200px” theme=”light” playlist=”false” playlist-continuous=”false” autoplay=”false” live-autoplay=”false” chapters-image=”true” episode-image-position=”right” hide-logo=”false” hide-likes=”false” hide-comments=”false” hide-sharing=”false” hide-download=”true”] Subscribe on Apple Podcast | Google Podcast | Android | Overcast | Spotify | Youtube 
You can listen right here on iTunes In our wide-ranging conversation, we cover many things, including:
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