EVERY SPOKEN WORD
150 min read · 30,484 words- 0:01 – 1:17
Beards, biological age, and why “getting younger” requires fixing everything
- AGAubrey de Grey
Three, two, one. Boom. Here we go.
- JRJoe Rogan
What's up, man?
- AGAubrey de Grey
How are you? What's up?
- JRJoe Rogan
Hey, did you trim your beard since I've seen you last?
- AGAubrey de Grey
No, I'm afraid not.
- JRJoe Rogan
I feel like you have.
- AGAubrey de Grey
No. It may be a fraction shorter, but that's only because it's been falling out more.
- JRJoe Rogan
It falls out?
- AGAubrey de Grey
Oh, yeah. I mean-
- JRJoe Rogan
Wow.
- AGAubrey de Grey
... I stroke it all the time, you know? It's compulsive.
- JRJoe Rogan
Oh. And so then you get these weird hairs that you have to-
- AGAubrey de Grey
(laughs) Well, actually, I don't notice it enough. I mean, it falls out slowly, you know, but-
- JRJoe Rogan
Yeah.
- AGAubrey de Grey
... I guess, you know, I guess there's a certain amount of attrition.
- JRJoe Rogan
So the beard's the same length?
- AGAubrey de Grey
Pretty much.
- JRJoe Rogan
Have you gotten any younger since I've seen you last?
- AGAubrey de Grey
Yeah, hard to say.
- JRJoe Rogan
Hard to say. But that is your, that is your business?
- AGAubrey de Grey
That's my business, yes.
- JRJoe Rogan
How many years has it been since I saw you? Four?
- AGAubrey de Grey
Uh, f- nearly five, I think.
- JRJoe Rogan
Five? Five years.
- AGAubrey de Grey
It was A- April of 2015.
- JRJoe Rogan
Mm. And you have not, you have not gotten younger?
- AGAubrey de Grey
I have not gotten younger. I-
- JRJoe Rogan
Have you maintained?
- AGAubrey de Grey
I think I've pretty much maintained, yes.
- JRJoe Rogan
Yeah?
- 1:17 – 4:14
Aging as accumulated damage: the “machine wear-and-tear” model
- AGAubrey de Grey
All right, so the fantastic answer to that question is there are no new revelations in terms of what we understand. Our understanding seems to have been pretty much complete already, like 20 years ago. The fact that we haven't found out any fundamental new stuff that we didn't know before then is fantastic news, because of course it means that we're unlikely to find anything out in the future either. It means that we are pretty much on top of the description of the problem, and therefore it's all about solving the problem.
- JRJoe Rogan
Is it b- possible to summarize the problem?
- AGAubrey de Grey
Sure.
- JRJoe Rogan
What is the problem? What causes human aging?
- AGAubrey de Grey
Sure, that's easy. So aging is simply the same thing in a living organism like you or me as what it is in a car or an airplane or any other simple manmade machine. It's a fact of physics, nothing to do with biology, that any machine that has moving parts is gonna do itself damage in the course of its normal operation, as an intrinsic consequence of its normal operation.
- JRJoe Rogan
Okay.
- AGAubrey de Grey
So in the same way that a car rusts-
- JRJoe Rogan
Jimmy's gonna bring that microphone up to you.
- AGAubrey de Grey
Sure. Is that good? Yep.
- JRJoe Rogan
Yeah.
- AGAubrey de Grey
Sorry.
- JRJoe Rogan
Just try to keep it about a fist from your face.
- AGAubrey de Grey
Yeah. So in the same way that a car rusts, uh, or, you know, accumulates junk in the oil or whatever, similarly the human body does damage to itself.
- JRJoe Rogan
Mm.
- AGAubrey de Grey
And again, just like a car or an airplane, the human body is set up to tolerate a certain amount of that damage so that we can get through to the point where we have kids before we start going functionally downhill.
- JRJoe Rogan
Hmm.
- AGAubrey de Grey
Whether mentally or physically. But after that, evolution doesn't care about us anymore, and therefore, we are only equipped to tolerate that much. And eventually the damage that's being done accumulates to a point beyond what the body's set up to tolerate, and that's when things start to go wrong and-
- JRJoe Rogan
So-
- AGAubrey de Grey
... we start to function less well.
- JRJoe Rogan
... what is the difference physically between a younger person and an older person in terms of their ability to recover from the damage of just regular, everyday life and exercise and abuse and running around?
- AGAubrey de Grey
Yeah, all that. So that's just one aspect of the difference between a younger person and an older person, so let me answer that question by stepping back one step.
- JRJoe Rogan
Okay.
- AGAubrey de Grey
So the difference ultimately arises from what the body is made of at the molecular level and cellular level. The body accumulates various changes that are chemical and biological consequences of what the body has to do to keep us alive from one day to the next, even starting before we're born. And those changes, the reason I'm using the word damage to, to describe those changes, is because eventually things don't work so well. So you're quite right that recovery from injury is one thing that doesn't work so well, but so are plenty of other things, whether it's how fast you can run or how, how fast you can think, you know, how strongly you can grip something, uh, how fast you can walk. Um, you know, all of these things become progressively less good. But the point is that the amount by which they become less good is pretty negligible until the age of 40 or 50. It's only then that the decline starts to accelerate.
- 4:14 – 9:35
Personal habits vs. biology: genetics, sleep, and a lot of alcohol
- JRJoe Rogan
So what do you do in your own life to try to mitigate that acceleration?
- AGAubrey de Grey
Yeah, I'm a really bad example of this, for two reasons.
- JRJoe Rogan
Really? That's crazy, but you're a... This is your business.
- AGAubrey de Grey
So there are two reasons why I'm bad at it.
- JRJoe Rogan
Okay.
- AGAubrey de Grey
The first reason is that I'm really well built. I'm just lucky. I'm just one of those hateful people who I can eat and drink exactly what I like and nothing seems to happen, and I don't even need to exercise to speak of, and, you know, I'm far, biologically far younger than I actually am chronologically.
- JRJoe Rogan
How old are you chronologically?
- AGAubrey de Grey
Chronologically, I'm 57. Um-
- JRJoe Rogan
How old do you think you are biologically?
- AGAubrey de Grey
Well, th- I'm told that I'm a, a good decade less than that.
- JRJoe Rogan
Hmm.
- AGAubrey de Grey
And this is what I get told every time I do these tests, which I've been doing for the past, let me see, 18 years. Um, yeah, so that's pretty good news. Um-
- JRJoe Rogan
So you're lucky.
- AGAubrey de Grey
Yeah, that's right.
- JRJoe Rogan
Genetically.
- AGAubrey de Grey
Yeah. But the other thing is, you know, I'm working hard to hasten the defeat of aging, and, um, maybe it's a net win. You know, maybe the amount that I'm hastening it is more than the damage I'm doing myself by, for example, not getting enough sleep.
- JRJoe Rogan
And you still drink booze?
- AGAubrey de Grey
(laughs) I still drink.
- JRJoe Rogan
How often?
- AGAubrey de Grey
Oh, I drink probably more than the average American.
- JRJoe Rogan
What does that mean?
- AGAubrey de Grey
(laughs) A few beers a day.
- JRJoe Rogan
A few beers a day?
- AGAubrey de Grey
And maybe, and maybe-
- JRJoe Rogan
What's a few?
- AGAubrey de Grey
... a whiskey or two. Yeah, three or four.
- JRJoe Rogan
Three? Three or four?
- AGAubrey de Grey
Yeah.
- JRJoe Rogan
Three or four beers every day?
- AGAubrey de Grey
Yeah, most days.
- 9:35 – 13:07
Life in California and the SENS approach: divide-and-conquer + philanthropic independence
- AGAubrey de Grey
I live in California now.
- JRJoe Rogan
Oh, you do? You live out here?
- AGAubrey de Grey
Yeah, I live in the Bay Area.
- JRJoe Rogan
Get the... What are you doing out there?
- AGAubrey de Grey
Well, that's where the foundation is based.
- JRJoe Rogan
Oh, okay.
- AGAubrey de Grey
Yeah, I've been over here for 10 years now.
- JRJoe Rogan
So what is, uh, a day-to-day life? What's a w- a normal day for Aubrey de Grey?
- AGAubrey de Grey
Well, there isn't really a normal day. I spend a ridiculous amount of time on the road, 'cause I view, you know, being a high profile member of this community, I view the outreach side of things, just educating people on this, as an enormously valuable and important part of my work. And also, it's something you can't delegate. Because, you know, conference organizers or interviewers for that matter, they always want the front man. Whereas on the science side, we- we've been able to hire extremely good people. And so I've been able to delegate that to a very large extent.
- JRJoe Rogan
Now, in terms of progress, like, what, what has to happen for there to be a shift in the, th- the biological age of people, where you could actually reverse it? Or even actually maintain the position they're at now for extended periods of time?
- AGAubrey de Grey
First of all, let me answer that last part. So reversing aging is actually going to be pretty much the result of maintaining it. There won't be a just you maintain it, because that would mean that you are repairing the damage of aging just exactly at the same speed that the damage is being laid down, which is ridiculous. You know, you'd obvious-... If you can do that, you can obviously do it a little bit faster than it's being laid down.
- JRJoe Rogan
Right.
- AGAubrey de Grey
So you don't really need to think about the maintaining part. Um, however, what we need is we need to be able to repair all of the types of damage. And because the human body is so very complicated, there are of course a lot of different types of damage. So it's a divide and conquer strategy. Any of these types of damage, at the molecular level, cellular level can perfectly well kill you more or less on schedule, however well we fix all the others. So since the beginning, SENS Research Foundation, my organization, has focused on the most challenging, the most difficult types of damage. Because basically the easiest ones are being worked on by other people. We have, you see, we set ourselves up as an independent charity. We're... So we're a charity, we're a public 501 (c) (3) , which means that if someone gives us money, they get a tax break. But we're independent, which means that we do not rely on peer review, government grants, or anything like that. We just rely on phili- philanthropy. The enormous advantage of that is that we're not competing with a lot of other people who have their own ideas about what to do. And in particular, the people who are deciding who wins that competition are not, um, you know... When you apply for government grants, it's terrible, you know. You end up having to basically-... emphasize really boring, low-hanging fruit just in order to have a chance at getting funded because people want to avoid funding things that don't lead to high profile publications soon.
- JRJoe Rogan
Hmm.
- AGAubrey de Grey
Um, so, you know, really ambitious, high risk, high reward stuff just doesn't get done and so that's ... So we focus on that because other people can't.
- JRJoe Rogan
That makes sense and that's very unfortunate that that doesn't get done outside of what you're trying to do.
- AGAubrey de Grey
Yeah, I mean, of course, this, this is a recognized problem.
- JRJoe Rogan
Yeah.
- AGAubrey de Grey
And NIH, for example, have tried to address it with awards, wi- with types of grants that are specifically focused on more, um, cutting-edge visionary stuff. But the magnitude there is ti- ... It's real tokenism. You know, it's less than 1% of the NIH budget.
- JRJoe Rogan
What's frustrating to you about th- the state of, uh, understanding repair and understanding the, the, the ability to fix things?
- 13:07 – 16:42
From persuasion to investment: private-sector acceleration and first clinical footholds
- AGAubrey de Grey
W- well, I'm not the kinda guy who gets frustrated very much. You know, I'm always a glass half full kind of person. So for me, what matters the most is the fact that the understanding that this is what aging is and this is how to deal with it has improved so much over the years. So I started putting out the idea that this was the way to go after aging 20 years ago. Uh, bef- up until then, the only game in town really was we've gotta make the body run more cleanly and generate this damage more slowly than it naturally does. And that's a very big conceptual difference, right? So it's not surprising that it took me maybe 10 years to really get the damage repair approach taken properly seriously by my colleagues in the scientific community. But by about 10 years ago, it was taken seriously and in fact over the past decade, people have been periodically reinventing the idea. And, you know, I don't necessarily always get as much of the credit as I probably ought to have, but I don't care about that. The main thing is I don't have to persuade anyone anymore. People get it, that damage repair is at least, if not the way to go, at least a very promising way to go. So really what happens next is convincing people outside of the community, right? And there, there's been enormous progress as well. So when you and I spoke last, five years ago, really that was the end of the story. I'd pretty much won the scientific argument, but still no one was really listening. And then over the past five years, the huge thing that's happened is the private sector interest in this has taken off. So investors have been coming along. Typically, it's been led by the angel investor types, the seed investors, people who are willing to do really high risk, high reward stuff, but they understand that we are getting close enough that this is the next big thing, that we will actually have bonafide and genuine rejuvenation medicine in the foreseeable future.
- JRJoe Rogan
How foreseeable?
- AGAubrey de Grey
Well, you know, some of it's already in clinical trials.
- JRJoe Rogan
Like what kind of stuff?
- AGAubrey de Grey
So for example, the stem cell therapies now being used-
- JRJoe Rogan
Mm-hmm.
- AGAubrey de Grey
... for aspects of aging with a really clear understanding of how they're going to work. Parkinson's disease is a great example of this-
- JRJoe Rogan
Yeah.
- AGAubrey de Grey
... where stem cell therapy is the right way to go and it's in clinical trials. Something that's been in the news a lot over the past couple of years is senolytics, which are drugs that selectively kill what are called senescent cells. So these are cells that hang out in the body in a bad state, where they're doing more harm than good. They're, not only are they not doing what they're supposed to, they're also secreting nasty stuff that damages their neighborhood. And so drugs have been developed that are seemingly pretty good at getting rid of those, and they're in clinical trials as well. Most ... And so we don't wo- ... We used to work on that area. We basically do no work on that area anymore, hardly any. Um, and we may end up doing none at all a couple of years from now just because-
- JRJoe Rogan
Why is that?
- AGAubrey de Grey
Because other people are doing it-
- JRJoe Rogan
Mm-hmm.
- AGAubrey de Grey
... and so our money is better spent doing the stuff that's still at an earlier stage. And beyond that, um, you know, we are able even for things that are a couple of years behind that, so wo- won't be in clinical trials for another year or two, um, we've been able even then to get investors interested so that we can actually spin the projects out as start-up companies and focus on the things that remain. And it's not just us, of course. There's lots and lots of ... I mean, literally more than, way over 100 other companies now that I work with 'cause they're not spin-outs from my foundation but they are, um, you know, doing closely aligned work. And so I'm, I'm literally spending probably a day a week on average, um, just making introductions between, you know, en- entrepreneur founders, you know, scientific founders of, with, with great science and investors who wanna get involved.
- 16:42 – 22:26
Stem cells for aging vs. acute injury: Parkinson’s as the clearest case
- JRJoe Rogan
The, uh, stem cell therapy is fascinating to me because I've had some personal experience with it. Um, I've had some injuries that I cured with, uh, well, doctors cured with stem cells in a remarkable way. Where the point where I, I was told that I need shoulder surgery-
- AGAubrey de Grey
Mm-hmm.
- JRJoe Rogan
... and, uh, I had a, a large rotator cuff tear-
- AGAubrey de Grey
Mm-hmm.
- JRJoe Rogan
... and it's gone.
- AGAubrey de Grey
I know, it's incredible.
- JRJoe Rogan
It's amazing.
- AGAubrey de Grey
But that's not really what I'm talking about. That's gone really well and-
- JRJoe Rogan
You're talking about ne- neurodegenerative diseases and-
- AGAubrey de Grey
So, well, the big difference, it's not necessarily brain versus anything else. What I'm saying is that what you got was using stem cells to treat an acute injury-
- JRJoe Rogan
Mm-hmm.
- AGAubrey de Grey
... right? A tear. And that's what stem cell therapies have been developed the most for so far, um, a- and have shown the most promise for. But now we're going to the point where we're in a position to use stem cells to address certain aspects of aging. In other words, certain aspects of slow, steady, progressive decline that happens throughout life.
- JRJoe Rogan
Through intravenous use?
- AGAubrey de Grey
Th- well, not necessarily intravenous. So let me talk about the Parkinson's disease case in a bit more detail. So what Parkinson's disease is driven by is the loss of a particular type of neuron. So of course, in the brain there's lots of different types of neuron. There's one type called a dopaminergic neuron and they exist just in one specific, very small part of the brain called the substantia nigra. So it turns out those neurons, they ... Well, because they do a lot of work basically, um, they die at a much more rapid rate than other types of neuron. So (clears throat) we end up, all of us, with maybe-... a quarter of those neurons that we had when we were young adults having gone by old age. That's okay. That, that amount of margin of error is tolerable in the system. It just doesn't, doesn't have a con- a consequence. But of course, as with everything in aging, some people have the problem accumulate faster than others, and so some people by old age will have lost maybe three-quarters of their dopaminergic neurons, and that is what gives you Parkinson's disease. So what is stem cell therapy? If you think about it, what it is basically you put cells into the body that have been programmed, have been got in ... Have been, um, developed into the right state in the lab so that they know what to do when you inject them. They know, like, to divide and to then transform themselves to differentiate into the right kind of other cell. So what has been developed is dopaminergic precursor cells, stem cells that know how to become dopaminergic neurons. And those are injected into this one place, the substantia nigra, and they do what ... They do that thing.
- JRJoe Rogan
So they're injected right into the brain?
- AGAubrey de Grey
That's right.
- JRJoe Rogan
Wow.
- AGAubrey de Grey
So actually this was first tried more than 25 years ago. There was a clinical trial in Sweden because people knew what Park- what, what was ... That this was driving Parkinson's disease, so they knew this ought to work. But of course back then we knew almost nothing about how to manipulate stem cells in the laboratory. So what they did was, these people, they took cells from the right part of the brain of aborted fetuses. Right? And they just injected them. Now this was enormously speculative because, you know, first of all, the brain of an aborted fetus is very pu- very ... Has, has hardly developed at all, right? And so just taking the right cells from kind of the right place was hit-and-miss. And sure enough almost all the time there was no effect because, you know, they just didn't get the right kind of stem cell, but occasionally it worked. Occasionally patients got lucky and got some of the right kind of stem cell.
- JRJoe Rogan
How often?
- AGAubrey de Grey
Well, I think there was a single-digit number in the, in the clinical trial that was done, like maybe three or four. But the question was how good was the effect when there was any effect at all? And the answer was astronomical.
- JRJoe Rogan
Mm.
- AGAubrey de Grey
So a couple years ago there was actually a retrospective written by the group that did this clinical trial and it was written specifically about the first responder, the first person who really got lucky and responded well. And it was written on the, on the occasion of the 25th anniversary of that person being treated. What happened with that person was they were treated once, just got one injection, and the Parkinson's symptoms went away so well that the person was taken off their prior medication. There's a standard medication for Parkinson's called L-DOPA which is a precursor molecule for dopamine. Um, they were just taken off it. Again, no symptoms. Symptoms gradually started coming back after 15 years. So 15 years with no symptoms at all just from one injection.
- JRJoe Rogan
Wow.
- AGAubrey de Grey
That's about as good as you can get. So of course now that we know so much about how to manipulate stem cells before we inject them and therefore how to inject the right kind of stem cell, um, you know, people are very optimistic and that's why there are clinical trials already ongoing right now.
- JRJoe Rogan
That's fascinating. So what's really interesting to me is that during the time this person had this one injection, the rate of progress, the amount of understanding of-
- AGAubrey de Grey
Mm-hmm.
- JRJoe Rogan
... how to manipulate these cells and make them exactly what you want has increased and-
- AGAubrey de Grey
Well, that's right.
- JRJoe Rogan
... probably shall still increase, and considerably.
- AGAubrey de Grey
That's right. And so what I was saying about we ... How SENS Research Foundation is moving increasingly away from bothering work on senolytics because other people are doing it, that was already true when we started the foundation in respect to stem cells. We didn't need to. Everyone else-
- 22:26 – 27:33
How soon? Aubrey’s probabilistic timeline, the funding bottleneck, and cultural denial
- JRJoe Rogan
That's very exciting. So you, when you look at your future at 57 years old and you think of yourself at, at 77, do you, do you think you're gonna be the same?
- AGAubrey de Grey
(laughs) Well-
- JRJoe Rogan
If you had to guess.
- AGAubrey de Grey
So in order to answer that I have to come back to what I said about this being a divide and conquer problem, and the fact that we need to fix all of these things in order to really give the proper results in terms of biological age. Now that means that any speculation that I may make about the timeframe for when we get there is a speculation about the most difficult parts of the problem, and therefore it's highly speculative because the most difficult parts-
- JRJoe Rogan
Mm-hmm.
- AGAubrey de Grey
... are at the earliest stage and therefore there's ... There's more opportunity for things to go wrong between now and then so to speak.
- JRJoe Rogan
Right.
- AGAubrey de Grey
So when I am asked to give a timeframe estimate on this, I always make sure to emphasize that it's probabilistic, that what I'm giving you is a timeframe for when I think we have a 50/50 chance of getting a decisive level of comprehensiveness of these therapies. And at the moment that number is 17 years. Now-
- JRJoe Rogan
That's very specific.
- AGAubrey de Grey
Well, yeah. And it's ... It is, yeah. I mean, but the thing is what matters is how that number has changed over the time, over time. So I first started giving timeframe predictions about 15, 16 years ago, and back then I said 25 years. Right?
- JRJoe Rogan
Mm-hmm.
- AGAubrey de Grey
So it's only come down by eight years in 16 years which sounds like bad news, right? But here are two pieces of good news. First piece of good news is that it hardly came down at all for the first seven or eight years. It was like ... I would say, yeah, um, five years ago I was still saying 22, 21 years. So it's been ... It hasn't been, hasn't been slipping any further for a little while. And the reason why things have speeded up to parity is because the only thing that was slowing it down before was lack of funding-
- JRJoe Rogan
Oh.
- AGAubrey de Grey
Beforehand, you know, I was always saying, "This is how fast the science allows the problem to be solved." But the science only allows the problem to be solved if the science can be done, and that req-... and ult- ultimately, biomedical research is inherently expensive. And we are just not able to pull in as much money as we need for this. So it's-
- JRJoe Rogan
That's interesting because it seems like that would be something that most people would have a vested interest in funding.
- AGAubrey de Grey
You don't say. Um, and sure, over the past five years, as I mentioned, as things have become investable, things have changed a lot. Every time we end up being able to spin a project out from our lab into a private company, another digit gets put on its budget, like, overnight, just because it's so much easier to get people to write a check if they think there's a chance, even a really small chance, that they'll get their money back in-
- JRJoe Rogan
Hmm.
- AGAubrey de Grey
... spades sometime later. Um, you know, th- I mean, I guess that's what you would expect. Um, but yeah, I mean, of course, the other thing that we always are up against is the mindset that people have got into about aging, that they've needed to get into for all these millennia that we have been unable to do anything about it or have any prospect of doing anything about it ev- anytime soon. You know, what are you gonna do? You've got this terrible, ghastly thing that's gonna happen to you in the distant future, and, um, you can't do anything about it. So you've gotta put it out of your mind, 'cause you're not gonna spend, you don't wanna spend your life being preoccupied by it. So you've gotta find some way to, to, like, not think about it and get on with your miserably short life-
- JRJoe Rogan
(laughs)
- AGAubrey de Grey
... and make the best of it, right? Um, and, of course, the on- the only way that one can do that is by somehow denying, somehow tricking oneself into denying that this is such a big deal. You know, and thereby pretending, for example, that it's not really, like, a medical problem at all, you know, and that it's, like, inevitable and universal and natural or alternatively saying, "Well, okay, maybe we could fix it if we tried to, but it would be a bad thing," that aging is some kind of blessing in disguise. And that's where all this-
- JRJoe Rogan
Yeah, I hate that nonsense.
- AGAubrey de Grey
Yeah, and that's where all this stuff comes from about, oh dear, where will we put all the people, or how will we pay the pensions, or won't dictators live forever-
- JRJoe Rogan
(laughs)
- AGAubrey de Grey
... or won't it be boring, you know, you know, which I have to spend my whole life contending with.
- JRJoe Rogan
How do you say, well, how do you get over the dictators living forever one?
- AGAubrey de Grey
Well, you know, last time I looked, dictator was fairly high on the league table of risky jobs.
- JRJoe Rogan
(laughs)
- AGAubrey de Grey
You know, I mean, not a lot of dictators die of aging in the first place, and furthermore, the ones that do die of aging, they tend to have organized their succession in advance anyway, so it's as if they were already immortal. So, I mean, come on.
- JRJoe Rogan
Well, not only the percentage of dictators versus the percentage of regular people is so incredibly small, to not cure aging because of dictators seems like the dumbest idea ever.
- AGAubrey de Grey
Well, there you go. I mean, but people are s- people really, you know-
- 27:33 – 46:31
Is aging a disease? Semantics, chronic conditions, and why one-off cures mislead
- JRJoe Rogan
It's, it's essentially a disease that we all get.
- AGAubrey de Grey
Yeah, I mean, so I have to be very careful with the word disease.
- JRJoe Rogan
Okay.
- AGAubrey de Grey
Some p- some people aren't. So you've had David Sinclair-
- JRJoe Rogan
A mortality, yes.
- AGAubrey de Grey
... on the show. He's been a great friend of mine for 20 years.
- JRJoe Rogan
I love him.
- AGAubrey de Grey
Um, um, we've, yeah, we have a very similar attitude to, you know, authority. We don't think much of it. Um, and so we tend to push the boundaries a bit, both of us, in our, in somewhat different ways. So he, actually, h- his view of calling aging a disease is a bit different from mine. He's more comfortable with it. I tend to feel that the pro- there's a problem with calling aging a disease, which is that it makes it sound like it's something that can be cured with one-off therapy, uh, like, like, you know, an infection.
- JRJoe Rogan
Mm-hmm.
- AGAubrey de Grey
Um, which isn't, which it isn't. It's a side effect of being alive, and as such, it's something that, you know, you can repair, you can stave off, but you have to do it periodically because the damage is gonna continue to be created. Um, and, you know, the reason why that's important is that it determines what kind of, what kind of medicine we look for. A lot of Alzheimer's research, for example, in fact, I would say most of Alzheimer's research, has been predicated on this kind of mistake, on the idea that if we can just cure Alzheimer's, then it, you know... Uh, and so I would say that, actually, it's not that the word disease is used too narrowly and should be broadened to include aging. Rather, it's the other way around, that the word disease is used too broadly and should be narrowed so as not to include things like Alzheimer's that are actually parts of aging. Because really the difference between the progressive chronic conditions like Alzheimer's that we call diseases and the ones that we don't, like, you know, loss of muscle or decline in the immune system or whatever, you know, the only difference is semantic. Some of them are, you know, they're both parts of aging. They're just, some of them are ones that we've chosen to give disease-like names to.
- JRJoe Rogan
What would you call aging if you don't call it a disease?
- AGAubrey de Grey
Well, I call it a medical problem.
- JRJoe Rogan
Hmm, okay.
- AGAubrey de Grey
Right? That's all I call it.
- JRJoe Rogan
Okay, that's pretty pure.
- AGAubrey de Grey
Yeah.
- JRJoe Rogan
Yeah. Um, in, in terms of potential future treatments, stem cells seem to be very promising. Are there, are there other competing treatments that you think are equally promising or it's-
- AGAubrey de Grey
Oh yeah, oh sure, but they're not competing. So, um, so as I said, because this is a divide and conquer problem with a bunch of different types of damage, all of which we need to fix, then we need to look at the, at what fixes are available for each individual type. So what stem cells are there to fix is cell loss, where cells are dying and they're not being automatically replaced in the body by cell division.
- JRJoe Rogan
Have you personally experienced any stem cell therapy?
- AGAubrey de Grey
No, I haven't done any therapies of, for any, of any kind yet, but of course, you know, I'm paying attention.
- JRJoe Rogan
Yeah.
- AGAubrey de Grey
Uh, uh, uh, I'll see. You know, of course.... the way, the nature of aging is that because it's progressive and because it's only, it only causes functional decline after a certain point, there's a trade-off that one always have to keep in mind in terms of timing of the therapy between how badly one needs it and how rapidly the quality of the therapy is improving. So, you know, if I take a stem cell therapy now, then there's a chance that it'll be bad for me, for whatever reason, okay? Whereas 10 years down the road, I will still, uh, uh, you know, I won't have needed it for those 10 years. 10 years down the road, I may start to need it a bit more, but there, th- they will, it will have benefited from 10 years more of research and refinement.
- JRJoe Rogan
Hmm.
- AGAubrey de Grey
So, next one.
- JRJoe Rogan
So you're a cautious patient.
- AGAubrey de Grey
Oh, sure. I mean, I don't think anybody wants to be the first patient.
- JRJoe Rogan
I'm in. I'll t- I'll be the first guy.
- AGAubrey de Grey
(laughs)
- JRJoe Rogan
I'm already doing a bunch of stem cell therapies.
- AGAubrey de Grey
Well-
- 46:31 – 55:13
Overpopulation and carrying capacity: energy, food tech, fertility decline, and oceans
- JRJoe Rogan
Is there any concern or any thought whatsoever to the idea of exacerbating overpopulation?
- AGAubrey de Grey
Of course this is a legitimate question. The thing that's frustrating to me is that I've been answering it for 20 years.
- JRJoe Rogan
What is the answer?
- AGAubrey de Grey
And people still don't listen.
- JRJoe Rogan
Kill dummies?
- AGAubrey de Grey
(laughs)
- JRJoe Rogan
That's a good move, right?
- AGAubrey de Grey
Well, of course, a large part of the reason why, uh, uh, it's difficult to get the real answers across is because so much fiction has, science fiction has been written and of course movies, um, giving wrong answers, and um, you know, making a dramatic element out of it, you know?
- JRJoe Rogan
Yes.
- AGAubrey de Grey
Whether it's Blade Runner or In Time or, you know, any of these movies.
- JRJoe Rogan
Yeah, they all get it wrong, right?
- AGAubrey de Grey
They all make it as if it's act- they, they kind of reinforce the pro-aging trance, right? They make it as if life would be even worse if we had no aging. Okay, so what's the real answer? The real answer is very straightforward. It's simply that other technologies that are coming along already and will be established, well-established and ubiquitous before we get this to happen, are going to solve the problem, because they will increase the carrying capacity of the planet. Remember that the reason why we have too many people today and we've got environmental consequences is not because of lack of space. It's because of the amount of pollution that the average person generates. Specifically of course, you know, biggest thing being, uh, pumping carbon into the atmosphere. But um, of course, you know, whether it's plastics or whatever. And we're fixing that. You know, th- we've got solar energy and wind energy now that are completely exploding, and they're going to completely replace fossil fuels. And we got there without people even having to wake up and realize that climate change is actually quite an urgent problem.... we got there simply because the technology got to be good enough that the production of a kilowatt hour of, uh, of energy is actually cheaper with these renewable energy mec- mechanisms than it is from fossil fuel. And of course, it's not just that, it's also agriculture. So artificial meat, you know, within not very long, it's gonna be both tastier and far cheaper than r- regular meat. And the amount of, um, space we're gonna save, not l- let alone the amount of methane that we're not gonna be generating is going to, you know-
- JRJoe Rogan
I haven't heard anything saying it's gonna be tastier. Have you?
- AGAubrey de Grey
Of course it's gonna be tastier.
- JRJoe Rogan
How so?
- AGAubrey de Grey
Well, I mean, how would it be popular if it were not tastier? Right?
- JRJoe Rogan
Tastier?
- AGAubrey de Grey
Yeah.
- JRJoe Rogan
I don't think it necessarily would have to be tastier.
- AGAubrey de Grey
Well, as tasty would be good, but tastier would be better, right? (laughs)
- JRJoe Rogan
(laughs) I guess.
- AGAubrey de Grey
Right?
- JRJoe Rogan
I guess.
- AGAubrey de Grey
And, and of course, it's not just that. You know, there's, you know, cheap desalination, there's, um, you know-
- JRJoe Rogan
Mm-hmm.
- AGAubrey de Grey
... uh, plastic-eating bacteria.
- JRJoe Rogan
Yes.
- AGAubrey de Grey
All of these things are coming. And so there is no way that one can make a realistic, plausible argument that denies that the carrying capacity of the planet will rise far faster than the population. We don't even-
- JRJoe Rogan
I agree with you to a certain extent, but-
- AGAubrey de Grey
We don't even need to take into account other things, like the fact that fertility rates are coming down everywhere.
- 55:13 – 1:11:21
‘Anticipate the anticipation’: the sudden social and political shock of believable rejuvenation
- JRJoe Rogan
Have you thought about what the future looks like when people live to be 4 or 500 years old? Like, how... first of all, how wise will people be?
- AGAubrey de Grey
Mm-hmm.
- JRJoe Rogan
That's what's really interesting 'cause-
- AGAubrey de Grey
So, okay, so here's, here's a really important thing that I wanna get across. When we think about longevity... Well, actually, three things I wanna say. First of all, longevity is a side effect of health, right?
- JRJoe Rogan
Right.
- AGAubrey de Grey
So, you know, a huge amount of the so-called debate that goes on about the desirability of all of this just goes away when you remember that people actually quite like being healthy. But in terms of how the world will be, which is the question you asked, there's two questions here. One question is, how will the world actually be? And the second question is, how will people in the near term expect the world to be? And the reason why those two questions are, are important to distinguish is because the question of how the world will actually be is very obviously completely unanswerable even if we look 50 years in the future. I mean, if you look 50 years ago, right, how much of what we have today would've been predicted, right?
- JRJoe Rogan
Yeah.
- AGAubrey de Grey
The world is completely different. And certainly, in terms of longevity, you know, we're only gonna be getting older at one year per year. (laughs) There won't actually be any 500-year-old people for another 400 years, right?
- JRJoe Rogan
Oh, really?
- AGAubrey de Grey
(laughs) Well, yeah. I mean, it-
- JRJoe Rogan
I don't know. I don't know what you're gonna be able to do.
- AGAubrey de Grey
(laughs)
- JRJoe Rogan
You, you think it's funny.
- AGAubrey de Grey
We're not, we're not gonna be able to change the pa- change the rate of the passage of time is my point, right?
- JRJoe Rogan
I understand what you're saying.
- AGAubrey de Grey
Right. But expectation is a completely different thing. And here's why that matters. There's gonna become a point, there's gonna come a point where people, in general, the general man in the street, starts to realize that they're probably going to live an awfully long time because they're not gonna just get progressively sicker as they get older. And, you know, lots of other reasons are gonna exist why they're gonna live a long time. Like we're gonna have self-driving cars that pretty much eliminate, you know, road accidents and so on. So they're going to want a lot of different things than what they wanted when they thought they were gonna live only slightly longer than their parents. They're gonna want very different pension plans, very different life insurance, health insurance, very different inheritance arrangements. And these are huge, big-ticket items, right? They basically drive the global economy. So policymakers and decision-makers around the world had damn well better be ready for that shift in public expectation of how long they're gonna live, right?
- JRJoe Rogan
Yes.
- AGAubrey de Grey
Now, therefore, it is absolutely critical to estimate and to communicate the estimate of how soon that shift in public expectation is going to occur. Which means how, well, what events have to happen, how much progress needs to happen in order for that, in order to, in order to cause that shift. Now, this is where I am terrified because I think it's gonna happen really soon. I think it could easily happen in the next three to five years. And that when it does happen, it's gonna happen incredibly suddenly. Here's the sequence of events that I think is gonna happen. Step one, we're going to have sufficient progress in the laboratory or the clinic that most of my scientific colleagues are going to be willing to come out and say, more or less, "Yeah, Aubrey de Grey was right all along." They're gonna say, "Yeah, you know, it's a-"
- JRJoe Rogan
You're very excited about that.
- AGAubrey de Grey
No, I'm terrified, and I'm gonna tell you why.
- JRJoe Rogan
You're a little excited. A little excited.
- AGAubrey de Grey
I mean, I know I have been a...
- JRJoe Rogan
(laughs) Okay.
- AGAubrey de Grey
Recognition is never something that's driven me. Um, um, but yeah, they're gonna, they're gonna come out and say, "Yeah, it's only a matter of time before we lick this aging thing." Now, what do you think is gonna happen next? You're our media guy, right? Here's what I think is gonna happen, but I want your, uh, I wanna know whether you think I'm right.
- JRJoe Rogan
Okay.
- AGAubrey de Grey
I think the next thing that's gonna happen is that real opinion formers, people like you, people like Oprah Winfrey, are going to hear that being said and written, you know, in the media, and they're gonna say, "Oh, shit. This is actually gonna happen." And they're gonna say so on air, and they're going not only to say s- say what their opinion is, but they're gonna say what they think people ought to do. In particular, they're gonna say, "Well, look, you know, let's actually... if we're, if, if it's only a matter of time, the, uh, if we're losing 110,000 people every day worldwide to this phenomenon, then we do kind of have a bit of a moral obligation to make it less time if we can." So my sense is that once that happens, the following day, it's gonna become impossible to get elected unless you have a manifesto commitment to, you know, have a war on aging, you know, pr- throw proper money at this. I mean, I really mean a proper war on aging, not just like the war on cancer was. Lots of money, not just to do the research but also to frontload all of the investment in infrastructure, and, you know, training of medical personnel and so on, okay? And everyone's gonna know it.... like the world, the public is going to make that switch I just mentioned of expectation, like at once. So it's gonna be ridiculously sudden once it happens. And the first step is going to be that shift in what my colleagues in the biogerontology community feel able to say on camera and on stage. Now, therefore, the question is what amount of progress is gonna be required for that to occur? Now here's the thing, there aren't very many of us. It's a small field. The number of people at the top of the field who actually talk to the media quite a bit is, you know, a dozen maximum. There's me, there's David that you've had on the show, there's, you know, very few others. And we all know each other. We're all good mates, right? So we know exactly where our heads are, you know, what the drivers are. The number one reason why my colleagues don't already say what I say is funding. The fact that unlike me, those people are reliant for most of the money that drives their research on peer-reviewed government money, government grants. And they just won't get them if it's possible to accuse those, accuse them of saying irresponsible things to the media, things that get people's hopes up unduly.Remember there's hardly en- There's n- there's nowhere near enough money. There's less than 10% of the necessary money to fund research at the moment. So the committees that decide who gets money and who doesn't are always desperately scouting around for reasons to say no-
- JRJoe Rogan
Hmm.
- AGAubrey de Grey
... that can be justified. And saying, "Oh, this guy says irresponsible things to the media," is a totally safe way to say no. Right? So anyway, so this is, this is the problem. This is why my colleagues have to be really pretty curmudgeonly. Even David. David is probably the person out of my colleagues who pushes the envelope as much as possible out of people who have regular faculty positions. But, you know, he's just written a book, which I see you have on your shelf-
- JRJoe Rogan
Mm-hmm.
- AGAubrey de Grey
... called, you know, uh, Why We Age and Why We Don't Have To. It, he could not have written that book with that title five years ago-
- 1:11:21 – 1:16:03
What evidence would flip the field? Late-life mouse rejuvenation as the benchmark
- JRJoe Rogan
Yeah, well sequentially would be fun. I, it would be really interesting to take up a whole new career at 70, you know? And so this three to five year timeline, what, what makes you think that three to five years from now is when all this stuff will take place?
- AGAubrey de Grey
Well, of course it's subjective.
- JRJoe Rogan
Yes.
- AGAubrey de Grey
It's based on, um, you know, um, aggregating a whole bunch of different areas of research. But of course I'm fairly well-informed about where research currently is and how rapidly it's moving in a var- variety of different areas. And so just you know, just I'm putting all that together in my head and I'm saying, "How soon are we going to be able to take mice that normally live let's say two and a half years and do nothing whatsoever to them until they are one and a half, and get them to on average live to four instead of two and a half?" Right? Now if you can... And of course those extra years would be healthy years because we would be rejuvenating the mice, right? So I believe that that would be sufficient. And even, that's actually a little bit conservative. I think a less dramatic breakthrough than that might be enough to switch most of my colleagues over that, get them over the fence. Um, but I think that would definitely be enough. And I think that that is close.
- JRJoe Rogan
What, what was the research done with mice with myostatin inhibitors? Did that not increase lifespan as well?
- AGAubrey de Grey
So yeah, sure. I mean of cour- a lot of things have extended, uh, extended lifespan a fair bit. But what we have at the moment is not...... all the components of what I just said. If you do something genetic to mice, or if you do it s- you know, to them throughout their lives, then we can already get that year, year and a half out of mice, certainly a year. Okay. But not if you start at 18 months. If you start at 18 months, y- the best we can do is maybe four months. So that's the difference. You've got to be able to start late and get the big extension. And you're not gonna get that without bonafide rejuvenation.
- JRJoe Rogan
Hmm. So that's not gonna come by way of genetics?
- AGAubrey de Grey
Well, e- even if it did come by way of genetics, it wouldn't matter. It wouldn't persuade my colleague or me that we were on the brink of doing it for humans who have the misfortune of being already alive.
- JRJoe Rogan
Hmm. So the rejuvenation is gonna come through some sort of biologics.
- AGAubrey de Grey
Well, yes, through the kinds of things we're working on that I mentioned earlier.
- JRJoe Rogan
Yes.
- AGAubrey de Grey
Stem cells, gene therapy to do various things, to introduce, for example, bacterial enzymes that can break down waste products.
- JRJoe Rogan
Mm-hmm.
- AGAubrey de Grey
Senolytics that I talked about, pharmaceuticals to do other things.
- JRJoe Rogan
Um, what about the use of CRISPR?
- AGAubrey de Grey
Sure. Well, CRISPR's a very p- very important part of this. So...
- JRJoe Rogan
Can you please explain what CRISPR means for people who don't know what we're talking about?
- AGAubrey de Grey
Sure, yes. So CRISPR is a technology that was first developed about eight years ago now, and it is the exploitation of a bacterial mechanism that allows bacterias to defend themselves against viruses. Uh, essentially how it works is that it allows us to change the sequence of our genome in a particular cell, um, in a very specific way. T- basically, it's often called gene editing. And there are other technologies for gene editing that, uh, already existed before CRISPR that are very laborious, very expensive, and very clunky. This is far, far cheaper and easier to use. So what that does is it allows us, for example, to inactivate a gene, or for that matter, to, um, change the sequence of a gene from a mutant form into a normal form, so that it works when it was previously not working. Now, doing that in the laboratory, in a Petri dish, is fair enough. The question is can we do it in the body? And initially, no. Initially, this technology was too error-prone. It was prone to do what, what George Church has called genetic vandalism, and, um, make, uh, have what's called off target effects. In other words, basically do other changes to the genome elsewhere that you didn't want. But, of course, people have known this and people have been working really hard to improve the technology, and it's getting to the point now where it's possible to actually use it on humans maybe. You know, it's getting, it's getting there. Um, now, you can't do everything with CRISPR. One thing you definitely can't do with CRISPR is insert new genes into the genome, and that's something we really need to be able to do. But actually, one of our big projects is a kind of two-step thing, where we use CRISPR to make a small change to the genome that allows us to insert large genes where we couldn't previously. Um, so yeah, so, so CRISPR is huge. And it's huge not only in aging research, but across the whole board of biomedical work.
Episode duration: 1:40:42
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Transcript of episode 9-z0kglwpwo
