Human Longevity 101

Yeah, no, it's not a joke. I said, I want to be prepared, so tell me what you want to answer. And they said — you know, it was a really good question. In fact, it was a terrific question. The answer is no. But maybe it'll happen one day. It's good to discuss that. Discussions like that happen with statins — should we just put statins in the water? Those things come up from time to time. By the way, there's no comparison between the effect of metformin and statins. Metformin is going to have a much bigger impact than statins. But statins are a good drug, and people are asking those questions. It's fine.

Yeah, this is a very interesting point. There's the UK Biobank — a huge collection of clinical data with genetic data, biomarker data, outcomes, diseases. I'm going to answer your point, but let me make a different example. We use the UK Biobank to ask specific questions. If you have high IGF-1, which is a growth hormone — that's how we measure the effects of growth hormone — is it going to be good for young people and for old people? High IGF-1 levels are always good for young people: they have less mortality, less of all kinds of diseases. And it's always bad for old people. We call it antagonistic pleiotropy — things that are good for you when you're young can turn against you when you're old. As we go through aging and there's a breakdown, we need to stop growth and start stopping the breakdown; getting this energy back into growth is not good for us. Why am I telling you this example? Because it's going to be the same with drugs. If we give growth hormone, we give it only to the young, not the old. And the same with metformin. We know that metformin after the age of 50 had good effects in trials. But do we know that before that age it doesn't have bad effects? Metformin lowers IGF-1 levels, and it's not good to lower IGF-1 in young people, right? So your question is absolutely right — when we give drugs is very relevant. I would really tell your friends: if you hear this and think, "wow, I should take metformin," I'm not sure it's safe. There are trade-offs, and part of the trade-off is age. So I wouldn't ask you to do that.

Well, first of all, the answer is no. But for me personally, as an MD — on the first day we learn to do no harm, right? We're always on the edge of doing more harm than good; it's always a balance. That makes us very conservative. The second thing in medicine is that there's no "always" and no "never," so we also become unsure of ourselves, which is a bit of a problem. Now, I'm playing the game of leading a major clinical trial, and my duty is to say: don't take anything before there's a clinical trial. That's what I usually say, and I'm not calling for anyone to be on metformin. But I am concerned about young people who don't understand that the mechanisms of aging — and the targets for aging — are different between young and old people, and that there are trade-offs.

So I'm looking at three things from a treatment perspective. One is the Dorian Gray state. Dorian Gray wasn't aging, but when he looked in the mirror, he saw his real age — the mirror didn't hide it. I'm pretending that I'm Dorian Gray: I look at myself and say, hey, maybe chronologically I'm this age, but actually I'm much younger. So I try it, and it works well for me. Those are drugs like metformin and rapamycin — the Dorian Gray drugs — trying to delay aging right now.

The second scenario, which is the hardest, is the Wolverine, or the Fountain of Youth: let's take you old, put you in a bath, and you come out young. Very, very difficult to do. That said, there are drugs like senolytics that, at least in animals, improve their health — not their lifespan, but their health. So when I say that if you target aging it can stop and even reverse, in this sense it does.

But the third scenario is the most interesting: it's Peter Pan. Peter Pan was forever young. The idea is that we take a 20- or 30-year-old, give them a treatment once a month or once a year, and erase their aging, so it's delayed significantly and they don't get old. I think that's going to be the easiest thing to do in 50 years. I don't think we're near it now — there's no model showing it's going to work — but this is probably where we're going. For now, we have to block aging as it comes on us. That's good, and we can and should do it, but it's never going to be as good as just staying young.

Well, I think about it as a curiosity, not as medicine. Personally, if you tell me I'll become an avatar — it doesn't attract me, really. I'm afraid there are things people are taking that are going to change who you are. One of the problems: if you're going to renew my neurons, you first have to download the information — my memories, my personality — and pass it to the new neurons. If I'm going to be a different person, I'm not really interested in that. I'm interested in my life, not somebody else's life. So the science fiction is cool, and technology and robotics are going to help us a lot — they're helping us already. I'm looking for technology that will help me age, but I'm not looking at becoming something else, because it's not attractive to me. I can see why it would be attractive to other people, but not to me.

Well, I think our maximal lifespan as a species is about 115 years. We argue about it, because somebody lived to 122, but statistically it's 115. And we die before the age of 78 now — so there are 37 years to realize before we even need to have that discussion. It's not going to happen in one day anyway. That doesn't mean our maximal lifespan has to stay at 115. On one hand, there's the second law of thermodynamics, which says things have a limited life, and there'll be a limit no matter what we do. But I don't think that means we can't go past 115. The example I gave you — that maybe at age 20 we can rejuvenate — is probably one way to say we might get over 150. Just as we got to 78 and got a bad deal of cancer and diabetes, we'll get to 150 and there'll be new diseases that make us miserable. It's going to continue like that. So if you ask me, do we have a lifetime capacity? Yes. And if you ask me whether that's going to stay — not necessarily.

I don't see how immortality happens without the fourth scenario you suggested — where we're so dependent on technology that we're out of the game anyway. And personally... let's say the Earth survives for another 12 billion years, which is debatable — some people even talk about 100,000 years. But if Earth stays, I'm becoming a little bit tired sometimes, you know? I've had enough. I really don't want to go through 12 billion years of presidential elections and all the politics. 12 billion years doesn't sound great to me right now. I think what most of us want is to live healthy for a long life and then die one day — not wake up one morning. I think that would be a very good goal and a very good life.

Well, I would work on the mechanism that erases aging in stem cells. I don't want to get too complex, but it's really different to take a stem cell and rejuvenate it versus taking a cell that's already established and has a purpose — a neuron or a liver cell — and rejuvenating that. We're not there yet, although some experiments suggest we could do it. So that's where I would go. Even better would be to rejuvenate old cells — not just keep young cells young, but rejuvenate old cells without hurting anything. The only problem is that when you use those Yamanaka factors, these rejuvenating factors, in models, they are prone to cancers. So safety is always going to be difficult, and you have to find out which factors will do it without causing cancer.

The interest from investors is huge. Biotech had a very bad year last year, but there's an exponential increase in funding for longevity biotechs. In fact, together with Jim Mellon in the UK and some others, we established the Longevity Biotech Association, which is basically the association that's going to help the industry. It has special needs — if you want to do aging, you need more runway, more money. People should know about it and be educated, and we should help them. We need to help the regulation, and we have to make sure there are enough geroscientists to advise companies. If you want to target one of the hallmarks, we can set you up with experts so you understand what it does and why it pays to do it. So the biotechs are going to push us harder. There are trade-offs, though: I can't get postdocs anymore, because they go for better salaries at those biotechs. I'm not just worried about my own research — I'm worried there won't be a new generation of geroscientists if everybody goes to biotech right now.

Now, if you're asking where I'd spend the money, there are two ways to look at it. One is moonshots — let's do some rejuvenation that starts early. That might be good, but it's a moonshot, it'll take time, it's not going to help anyone in the meantime, and we need help right now. So if there's anything I'd do with the money, I wouldn't only do TAME — I'd do TAME-like studies. I have a paper out now showing nine other drugs that could be gerotherapeutics. Let's do TAME-like studies for all of them. Another reason we need the money is that we need to see which biomarkers change with age and with therapy. We have biomarkers that tell you your biological age, but those won't necessarily change with treatment — unlike cholesterol or hypertension, where if you treat them you prevent cardiovascular disease or stroke. That's not the case for us. So we need those biomarkers, and we need many clinical studies to do it safely — not to kill anyone on the road — to get the biomarkers and accelerate what we can bring to the public right now.

Yeah, we're working on that too. Again, in the UK there's Andrew Scott at the London School of Economics, who published a paper this year that was amazing. I've been part of a group, and part of papers, showing what it means for medical costs in the last two years of life if you extend healthspan by a year or two. It's quite incredible — if people aren't going to the hospital, you get a huge benefit. But Andrew Scott said, wait a minute, that's not everything that happens. Because if those people aren't in the hospital, what are they doing? They're traveling, they're shopping, they're buying things for their kids and grandkids. The economic value — you're totally underestimating it. It's a saving of 300-something trillion dollars over several years. Unbelievable. If we could save that, we'd also have money to fix global warming. It's really quite impressive. And this is something we have to educate the government about.

So I'm involved in lobbying in the United States, and for me it was a little challenging. The good news was that longevity is something where — yes, politics is an issue — but there are some things everybody can agree on. Even the most right- or left-wing politicians want to show they worked across the aisle, and longevity is a good thing for that. On the other hand, in the United States science became controversial because of the vaccine, right? We had a president who said don't wear masks, don't take the vaccine, it'll go away — giving scientists a bad name. So I told our lobbyists, we have a problem with science. And they said, no, you misunderstood: the politics here is because you forced somebody to take a vaccine. But if you develop a medicine — well, if you want to be sick and die early, fine, you don't have to take it. That's okay.

Yeah — Asian countries like Japan, because they're old and have almost no young people coming up. And China, because they prevented the second child for decades, so they have a huge number of old people. I think that's a very important motivation to improve the function of the elderly and decrease old-age spending; it's very much necessary for them. But I can't say they're biting — or at least I don't see it. It's hard to get into some of them. Although they should be desperate, I don't know that I'm helping them much. With Singapore, I was trying to tell the Ministry of Health — this was when Trump said "America first" — I said, well, in longevity, let's do "Singapore first." But then you realize Singapore is a relatively small country. They don't want to take on the tasks that are easy for the United States to do; they can be the first-second, but not the first. I think the UK is playing that game in part, too, although the UK is politically much more ready and accepting of geroscience. There's Tina Woods, who's leading longevity from a social and parliamentary perspective. They're ready for it — they understand the problem and where it's coming from.

There are two things that happened in my life that I think helped me be successful. The first is that I went to the army — I went like everybody else has to. For a lot of people, and certainly for me, the army is a place you go at 18 where, on the first day, you're nothing, you're zero. There's a guy two months older than you telling you when to brush your teeth, when to eat, when to go — making your life miserable. You're zero. And in three years, I became the chief medic of the army. There was an opportunity for growth: after three years I had my office, my secretary, my car, I did inspections in helicopters. It was a whole lifetime. And that gives you this generic perspective — okay, I've done it once, I'll do it again. I think young people grow much more slowly this way; they're part of the crowd and don't know they can go and make a difference. Once you've done it like that, it becomes generic. I could go to another country and start my research. I could go to the NIH and get my grant. Because I said, okay, I get the game, I'll play the game.

The second thing that helped me — and I say this because it's a personality issue — is that I never met a stranger. It's very helpful. I like people; I want to talk with them, know about them, help them. If there's a cost to it, I want to do it anyway. So if you're an introvert, no matter how smart you are, it's hard to be a leader, hard to be a collaborator. Those two things, if I have to choose, are what helped me most. And as I said, there's no advice in it — one was a life circumstance and one is personality. When people ask me what they should do, I always say: I'll tell you what I would do, so we can take that off the table and talk about what you should do — because you're a different person, with different experiences and a different personality.