Criticism has been a huge fuel for me, like a creative writing prompt. If you couldn't tell, that is Taylor Swift, who hasn't sat for an interview like this in a long time. I'm John Caramanica, one of the critics behind The New York Times' 30 Greatest Living American Songwriters Project. We interviewed some of the songwriters on our list, and these are not ordinary conversations. Watch all the video interviews for free and check out the entire 30 Greatest Living American Songwriters Project at nytimes.com slash 30 Greatest or in the app. From The New York Times, I'm Rachel Abrams, and this is The Daily on Sunday. Since the beginning of time, humans have quested for the fountain of youth. And these days, people are pouring billions and billions of dollars into products and therapies and treatments that are intended to reverse aging. And now, scientists may have gotten closer than ever before to treatments that could restore our youth. Today, I talk with my colleagues, Susan Dominus, who spoke with some of those scientists about their research and where the money that is funding it is coming from. It's Sunday, May 17th. Sue Dominus, welcome to The Daily. Thank you so much for having me. So, Sue, you cover the intersection of culture and science, and recently you have been focused on a very particular pursuit by a very particular group of people who are really interested in living longer. So I want to start with something very basic, which is, what is longevity science? So longevity science can be described in a bunch of different ways. I mean, there obviously are people who are researching peptides and who are selling supplements and who are urging health interventions. But it's basically the science of how we can live longer and how we can slow aging. And the research that I have become particularly interested in is something known as cellular rejuvenation. And just explain what that is. So cellular rejuvenation is basically this idea that we can take a cell that has aged and make it function like a younger version of itself. And one of the reasons why we believe this can be made to happen is because of something that happens every single time a baby is born. And what is that? Well, let me ask you a question. Why is a baby born young? I feel like this is a trick. I know. It seems intuitive, but it's actually not because although eggs and sperm are relatively protected from aging, a sperm cell, for example, does still bear the signs of aging that it inherited from the man who created it. And you can imagine that if that was true for every embryo that formed, that it inherited signs of aging, that eventually that aging would accumulate and accumulate and the species would go extinct. So it has actually been found that shortly after a sperm joins with an egg, there is this fascinating process by which the embryo essentially sheds the markers of aging that it inherited. And it is not at its youngest point at the second that that embryo has formed or that zygote has formed. It actually takes a little while and it sheds aging over a period of time and then it starts at what's considered ground zero for aging. You're saying basically an embryo ages backwards in a way? For a moment, yes. And then it starts to acquire signs of aging. And so what scientists are trying to do is harness that process in a way that can be useful for human health. Okay, so they're trying to replicate what happens briefly when an egg is inseminated. How far has science come on this front? Actually pretty far. In 2006, a researcher named Shinya Yamanaka at the University of Kyoto realized that by applying these unbelievably powerful genes that are highly expressed in embryos to the aged skin cells of a mouse's tail, he was able to revert those skin cells basically back to their embryonic form. That sounds incredible. It was a big enough deal that he won the Nobel Prize for it. Ah, okay. Well, there you go. But people weren't sure whether this discovery would ever have any application for human health because they knew that these genes were also associated with explosive cell division, in other words, cancer. And in fact, some researchers in Spain decided to see what would happen if they applied the Yamanaka factors to the body of a mouse. And what happened was that the cells of the mouse reverted back to this embryonic stage of development, which is fresh and young and wonderful, but the cells also became unspecialized. What do you mean by unspecialized? Basically they forgot how to do their jobs. They stopped being a heart cell or a skin cell, and they reverted back to embryonic form and eventually developed into these monstrous tumors called teratomas that are like these bits of various tissues, skin and hair and teeth, and their organ function fell apart. So it was fatal for these mice. Okay. So clearly, despite the fact that there has been a Nobel Prize awarded in this arena for progress, this is not a slam dunk. We are not at the precipice necessarily at this moment of rejuvenating cells. Well, in 2006, certainly we could rejuvenate cells, but not in a way that was going to be helpful for humans. So people just thought too dangerous, too cancerous, too messy, probably not useful. Let's move on to other things when it comes to longevity. Until a scientist at the Salk Institute named Juan Carlos Ipsizua Belmonte did some remarkable research in 2016. And tell us about him. He's a fascinating guy. He grew up in real poverty in Spain, picking fruit to support his family. Was briefly a professional soccer player in Spain. And then ended up in school and had a natural talent for science and was very interested in regeneration. He was very interested in a particular salamander that can regenerate its tail, for example, if you cut it off, including the part of the spine that's in the tail. He was interested in ways of creating organs or healing organs so that they could be in better shape for transplant. That was his background. And he was very interested in his Yamanaka factors. Those powerful genes we talked about earlier that Yamanaka used to rejuvenate the older skin cells of a mouse's tail. So he thought, okay, well, clearly we don't want to apply them in a way that's going to revert our specialized cells back into being stem cells or stem cell like cells, mainly because we don't want those nightmare tumors showing up in our bodies. We don't want the cells to forget how to do their jobs. Our organs would cease to function. So he thought, what if we just applied a little bit of the Yamanaka factors? Maybe we could take the cell not all the way back to its earliest stage, but maybe we could take it back to being like a teenager in its prime somewhere along the way. So he's tweaking the formula here basically. He tweaked the formula and kind of turned down the volume, you could say. And he applied the Yamanaka factors to mice that had been genetically tweaked to suffer from a disease that made them age very, very quickly. And he found that he was able to extend their lives significantly. But also, I mean, you could see it in the mice. They looked younger. They had less gray in their fur. Their muscles were stronger. They healed more quickly from wounds. And they were kind of rejuvenated and overall friskier. And the story goes that the lab technicians thought the old mice had been replaced by younger mice. That sounds very promising. So then what happens from there? So then the race is on to try to figure out how to use it in a way that is safe for humans. And I think most people in the field would agree that the next big breakthrough in the field comes from a very well-known longevity researcher who is also somewhat controversial named David Sinclair. What's his deal and why is he so controversial? So Sinclair is a professor of genetics at Harvard Medical School. And he, many of his colleagues would agree, has done really important research in the field of longevity. He's had very important breakthroughs. But he's also somewhat controversial, as I mentioned, because he's so enthusiastic about this research that at times his peers fear that he has maybe oversold the promise of where the science is right now. He is one of the important co-founders of the most important academy of longevity researchers. But he was also asked to step down from running it after he'd circulated on social media a press release from one of his biotechs that claimed that science had proven that there was a supplement that would reverse aging in dogs. And his peers did not feel that the research supported that. And he wrote a bestselling book that is super fascinating and holds a lot of really high-level science in it. It's called Lifespan, Why We Age and Why We Don't Have To. That subhead contains the kind of promise that makes his peers a little bit uncomfortable. It's also unusual, let's say, for a Harvard scientist to co-found, as Sinclair did with his girlfriend, a kind of wellness platform that relies on, let's say, non-mainstream practices like energy healing. There's still also a lot of discussion about a compound that he was a huge advocate of, known as resveratrol, that Sinclair maintains research shows can slow aging. But other people who tried to replicate the science did not meet success. And that biotech behind resveratrol was sold to GlaxoSmithKline, which is a major pharmaceutical company for a small fortune. But they eventually stepped away from pursuing resveratrol. So he's made a lot of important scientific breakthroughs. He's also made some choices that many of his colleagues are uncomfortable with, let's say. OK, so he's got a reputation for maybe getting over his skis a little bit, but also an innovator in this field. Correct. And recently, he's received a lot of recognition for a big break he had in the field of cellular rejuvenation. He had sort of a similar idea to the one that Juan Carlos Ipsuza-Belmonte had, which was, when we find a way to tone down the power of these Yamanaka factors, and his innovation was to say, well, what if we just dropped one of those factors? Let's only use three of them and not use the one that's most associated with cancer risk. And what if we applied those three to, let's say, the damaged eye cells of mice? And what he was able to do was restore the vision of mice, whom they blinded, using the same technology of cellular rejuvenation. And they did not find cancer growth in these mice. And it was a breakthrough. And it suggested that we can use the power of this kind of technology or medicine without necessarily incurring the risk. But obviously, of course, we know that mice studies are not human studies. So how is the science applicable to what these folks are trying to do with people? It's a great point. Mice trials often don't translate into humans. So they went to the next level, which was they tested the same process in monkeys, very small study, very small numbers. But they were satisfied that that was one more level of proof that this could be done safely, hopefully. So after these studies, which were very small, are done in monkeys. Sinclair's Biotech, which is called Life Biosciences, is able to get FDA approval to start a safety trial in humans to use the cellular rejuvenation to try to reverse blindness in humans who are suffering from glaucoma and another illness known as nion. So clearly this man is at the forefront. He's definitely at the head of the pack in getting this science into actual human trials. Whether that will be true for long, I don't know because there's a lot of interest in this field and there is a lot of money being thrown at a lot of other biotechs who are doing everything they can to catch up. And we are going to talk about all of that and who is funding this research after the break. We'll be right back. I'm Robin and I am excited to open my crossplay app. I'm challenging John, my colleague at the New York Times. Robin played the word grunge, which has a G, which is four points. She got that triple word multiplier. I'm going to take fax and make it faxes for 30 points. I might just take another two-letter word here with woe gets me at 23. I think this will put me back in the lead if my maths are mapping. I like to play it more from a strategic point of view and see where I can block the other player from scoring high. I'm pretty competitive. It's fun to beat friends and co-workers and also get to learn new words. Crossplay, the first two-player word game from New York Times Games. Download it for free today. I think he thinks he has this in the bag, but I'm not so sure. So Sue, obviously a lot of people want to live longer and healthier lives. There are many different wellness industries devoted to this topic, but when it comes to longevity science specifically, who is backing all of this research? The short answer is billionaires. Sam Altman of OpenAI has invested something like $200 million in a biotech called Retro Biosciences. The very wealthy Brian Johnson, who's a major tech VC, has made longevity science a kind of spectacle sport. He's injected himself with the plasma of his son, which is just one of a few crazy kinds of science capers he's undertaken. You have Peter Thiel, the billionaire who founded PayPal, talking about wanting to be cryogenically preserved. You have Larry Ellison, another billionaire and co-founder of Oracle, almost turning the island of Lenai that he purchased into a wellness mecca. And then there is what is thought to be the single biggest biotech startup in history at its launch, which is Altos Labs. One of his major investors is Jeff Bezos. And as part of your reporting, you actually visited this lab. What were you hoping to find out? I was trying to get a sense when I visited Altos of where they were pursuing the science. What was their hope? How big was their ambition? Are these people who were talking about we're going to extend life by 20 years, or are we just hoping to improve health across the board? Were they coming up with alternatives to the Yamanaka factors? Were they finding other ways of modifying their power? Those are some of the questions that I had. So I went to visit their lab in San Diego. They actually have several campuses, but I went to the one in this beautiful biotech park basically. And I was met there by Juan Carlos Ipsizua Belmonte. Belmonte, the Spanish scientist who first adapted the Yamanaka factors. Yes. They were able to recruit him and so many others that their success in that way has been described as one of the single biggest academic migrations in a field to private industry. And they were able to do that reportedly by offering something like million-dollar salaries to principal investigators. People were being offered huge resources, lots of runway time, and very high salaries. So what did you see? You know, I saw this beautiful, sunny, bright, light lab. I put on a lab coat and they seemed to be interested in showing me all the ways that they were using technology to do fast and highly predictive research. What do you mean by that? So a lot of the research that's done for ultimately human health is conducted on mice. And unfortunately, the vast majority of those findings do not actually translate into human applications. What works in a mouse does not always work in a human. So Altos is trying to improve the predictive ability of whatever research it's conducting by finding alternatives to animal models. So one of the things they showed me was a Petri dish that had rolling around in it what looked like a few grains of rice. But in fact, they were like almost mini human organs. I was looking at very tiny, tiny replica of human brains that had been essentially grown from stem cells and had many of the kinds of cells in it that you would find in a human brain. Just to give you a sense of how complete these kinds of replica are, if you were to look at an organoid of a human heart, it would actually beat. So they can manipulate those and do research on them more efficiently because they're made from human stem cells. So they're not looking, it's as close to our biology as they're going to get. And they also talked a lot about a virtual cell they had created, which requires huge amounts of AI, but allows you to do millions of experiments that otherwise would take years. And they can just sort of program in what if A mixed with B, add C, what would happen? And do that basically over and over and over again at high speed. So what did you make of all of this after you got this tour and saw all these innovations? You just get a sense of the vastness of the investment and the range of creativity that they're trying to apply and just the resources that they can use. So for example, one of the things that they are doing is trying to rejuvenate human livers. And in order to do that, you have to keep the liver viable long enough for the research to work. So far as I understand it, they've been able to do that for a longer period of time than has been done before, which could have huge consequences for liver transplants apart from whatever they find out about cellular rejuvenation. And did you get a sense about what they're hoping to accomplish a little bit more broadly? Like beyond just the liver, are they trying to get people, is all of this research to help people live to 300 years old? Or what did they tell you about their goals? Well, that's a great question because Ipsosu of Belmonte has been quoted saying that it's possible that the first person who will live to be 150 has already been born. But that is not the messaging that I was getting from Altos. The person who is their CEO, Hal Barron, is very well regarded in the field. And I think he is trying to keep expectations reasonable because much better to overdeliver and under promise than the other way around. And although I don't know this to be true and I can't really speak for him, I think if the idea we're trying to make people live to be 150, it makes a lot of people uncomfortable also. You know, it raises all kinds of other questions that maybe they don't want to have to get into. But it is also possible that they just think, look, we'll be really happy if we can extend human health and lifespan by two or three years. That would be revolutionary. That would be surpassing even what would happen if we could cure cancer. So I think that they are trying to distance themselves from this idea of we don't have to age. We could maybe live forever. We could live to be 150. That was not the messaging I was getting at all. It sounds like they're being really cautious, right? Like they're almost positioning themselves as kind of the anti-David Sinclair, just in terms of trying to come off as a little bit more sober. I think it's also possible that Hal Barron really does think it would be a miracle if we could merely extend, you know, human lifespan by three or four years. Or as he put it, if we could extend the health of a woman's ovary by just a few years, think about how life changing that would be for many women. So I think that he really does think it would be miraculous to accomplish those things and maybe just doesn't see the point in pie in the sky predictions that may never come to pass. Well, whether it's two years or a hundred years, there are obviously some implications of living longer lives and we're going to talk about those after the break. OK, so Sue, we have talked about the science. We have talked about the billionaires who are funding the science. We have talked about the competition. But what about us regular people? What can we reasonably expect to get from all of this within our lifetimes, perhaps? Well, you will not be surprised to hear me say that the answer is we don't really know. But even within the realm of possibility, there are kind of two versions. You know, there are the people who are hoping that cellular rejuvenation will be something that can really dramatically change our lifespan and our health span. How long we're healthy, right? Like maybe we can just keep reapplying cellular rejuvenation and people will end up living to be 150 or even no longer. That seems far-affetched to me, but there are actual scientists who think it's not outside the realm of possibility at some point. And then there is the more realistic expectation, which is, well, let's start with glaucoma. Is it possible that in the next decade even we could have a safe and effective treatment that relies on cellular rejuvenation? Yeah, I think that is within the realm of possible. That's why these trials are happening. Could that then be applied to organs so that people live a few more years? We're not expanding lifespan in some dramatic way, but we are curing disease so that people can be healthier for longer. And ultimately, that's the only way we can get to the end of the world. So that people can be healthier for longer. And ultimately, the goal is for people to live as healthy lives as possible that might be longer, but just to have less suffering so that those end years are less painful. You know, in this country at least, so much medical innovation is funded by the private sector. And as you told us, a lot of the money that is coming into this field is coming from high net worth individuals. So I wonder, does that matter at all, that distinction? Or is this just what you might expect in the United States when you have a group of people with money and interest and resources to put behind this kind of study? It's a little bit hard to know because I think there's never really been the intersection of billionaire investors in healthcare that also overlap so much with like, you know, control over technology and information access and privacy. And you know, it's very uncharted territory, but obviously industry has always been, you know, pharmaceutical companies have always been behind many of the great breakthroughs that happen. So it's not like our medical care is divorced from profit, far from it. To be clear, you know, these billionaires are investing huge amounts of money in R&D in the hopes that they can make a profit from it as well. And the only way they'll be able to make a profit from it is if the medical treatments are eventually widely available to the general population. Even if longevity science ends up revolutionizing the way that we age, we are also dealing with declining populations in many parts of the world, right? Like there is a real question, some might describe it as a crisis about how we are going to take care of our older generations when we do not have young people to do that. So if you're talking about making people live for longer and longer, what are the implications of that for our society beyond just the scientific and the health and the medical? Yeah, many philosophers are weighing in on this kind of question. I mean, there are economic questions, you know, our entire social security system is not designed for people to live to be 110. So what does that do to that economy? Philosophically, what does it mean when people are holding on to jobs for longer than they used to? Does that mean that there's less innovation, less freshness? People who are champions of longevity science would say, now, remember, people are not just living longer and living longer in unhealthy lives. They are living longer and healthier. That's the goal. And so they presumably maybe would be creative and nimble and active and engaged for many, many more years of their lives. And if we do have a population decline, maybe we need people to be able to function in a healthy way for longer to fill all those roles to keep the economy hustling along. It only becomes a crisis if there's a shortage of young people to pay for the medical care of these older people. But if they're healthier longer than that issue is not as pressing. Oh my God, are you saying I'm going to have to retire at 100 now because I'm going to have to keep working to sustain myself? So I because I'm so healthy, I'm going to want to travel and do things and I will not be able to not work. I think we haven't quite figured out the math on that. Yeah. You know, so when we first started talking about doing this story, one of the first discussions we had here at the daily was like, don't we all already know how to live longer? Like you eat well, you exercise, you don't stare at us at a screen all day. There's some very basic things that people know. But like so many other parts of our health, we want solutions, pharmaceutical solutions to basically account for the fact that we might not be taking care of ourselves the way that maybe we could. But for whatever reason, we can't or won't. I'm thinking, for example, about GLP ones, right? Like GLP ones are a shortcut to allow people to live much healthier lives. And this is seems like another way to kind of hack our bodies so that we maybe don't have to treat them as optimally as we should. Yeah, it is fascinating to me. I agree, because one of the things that how Baron said to me is we know that we can kind of reverse aging in people because we already know how to do it. And the way that we know how to do it is through diet and exercise, to which I wanted to say, then why again do we need to invest billions in this? It is kind of amazing how much we know exercise and diet and sleep and also sociability really do matter for people's general health. Right. I mean, my family feels very fortunate because my parents are now 88. And a few years ago, although my mom, I think is kind of knock on wood a super age, or and maybe my dad is too. But a few years ago, my siblings and I were starting to notice that he, you know, we could see that he was aging and, you know, in all kinds of ways. And then he and my mom joined one of these retirement communities that exists on the campus of a college. And suddenly they were socializing all the time and they were going out to dinner and they were my dad was taking an art history class and now he runs a film series. And my siblings and I feel he literally has been rejuvenated by this experience. It's been fascinating to watch, but not everybody does have that kind of luxury. And just as you say, we now know if GLP ones show us anything, it's that eating right is not just a matter of, you know, just try to eat less. It's just not that simple or there are, you know, there are food deserts and vegetables are in short supply. People are lonely and, you know, are under stress and that makes it hard for them to sleep well. So it's true that if this research could create some of those effects in a more accessible way and a way that's affordable and that really does allow people to live longer, healthier lives with shorter periods of suffering, that really could be transformative. Sue Dominus, thank you so much. Thank you so much for having me. Today's episode was produced by Luke Vanderplug with help from Tina Antolini. It was edited by Wendy Dorr and engineered by Rowan Nemisto. It had production assistance from Dahlia Haddad and contains music by Dan Powell and Marianne Lazano. That's it for the Sunday Daily. I'm Rachel Abrams. See you tomorrow. You
