Is Aging a Disease? Epigenetics with David Sinclair

Is aging a disease that can be cured? Neil deGrasse Tyson and cohosts Chuck Nice and Gary O’Reilly discover the field of epigenetics, the Information Theory of Aging, and curing blindness for mice with Professor of Genetics at Harvard Medical School, David Sinclair.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Neil deGrasse Tyson?

  Coming up on Startalk's special edition, we're going to discuss the epigenome and what it has to do with reversing the aging process. This is a future that may be closer than you think.

• 0:15Neil deGrasse Tyson?

  Welcome to Startalk, your place in the universe where science and pop culture collide.

• 0:24Neil deGrasse Tyson?

  Startalk begins right now.

• 0:28Neil deGrasse Tyson?

  This is Startalk's special edition. Neil deGrasse Tyson here, your personal astrophysicist. Got with me my usual band of co-hosts. Gary O'Reilly, Gary.

• 0:41Gary O'Reilly?

  Hey Neil, good to be here.

• 0:43Neil deGrasse Tyson?

  Former soccer pro, sports commentator, and Chuck Nice. Chuck, my favorite stand-up comedian. How are you doing Chuck?

• 0:50Chuck Nice?

  You can call me Friar Chuck since we're a band of merry men now.

• 0:55Neil deGrasse Tyson?

  As we frolic along the countryside, yeah. Today's topic is epigenetics and aging.

• 1:03Gary O'Reilly?

  Yeah.

• 1:04Neil deGrasse Tyson?

  We're long overdue for fielding this subject. And of course, we do what we normally do in Startalk is comb the landscape, looking for the particular expertise we seek. And let's find out in a moment who that is. But Gary, tell us how you and your producers came up with this idea.

• 1:26Gary O'Reilly?

  Robin Hood and I sat down with the band of merry men. With something we've been interested in doing and it's one of those things that's hiding, if you like, in plain sight again. But it is a fast emerging subject that we needed to get a handle on. Can we defy the march of time? Is our only hope of looking young and being younger a facelift? Could we in fact dial up or even dial down our own body's aging process? This is actually a really seriously heavy question and it's expert time. So Neil, if you would like to introduce our guest.

• 2:07Neil deGrasse Tyson?

  So this is a former Time 100 awardee. Time Magazine every year finds 100 people in the world who it judges to be the most important people, change makers, people who are shaping the present and future of civilization. Professor David Sinclair, David, welcome to Startalk.

• 2:26Speaker 03

  Hey, thanks for having me on. Good to see you again, Neil.

• 2:28Neil deGrasse Tyson?

  Again, yeah, I guess we bumped into each other at the Time 100 Dinner. They bring back a long, I'm an old timer.

• 2:35Chuck Nice?

  I'm sorry I missed you guys. I'm so sorry I missed you. Yeah. You're professor. I don't know what happened. I don't know why we didn't see each other.

• 2:44Neil deGrasse Tyson?

  You're professor of genetics at Harvard Medical School, co-director of the Paul Glenn Center of Biology and Aging Research, and author of Lifespan: Why We Age and Why We Don't Have To. So, first of all, let's get some groundwork here. What is, we've all heard of genetics, but what is epigenetics? And the only, epi, I think of EpiPen, I think of epicenter of an earthquake. So, how do you get epigenetics out of that word?

• 3:17Speaker 03

  Yeah, well, it's similar to the center of an earthquake. There are two types of information in the body. We know of genetics, genetics is the DNA. The epigenetics are the control systems that tell which genes to be switched on and off, which DNA to be looked out and unraveled and read by the cell versus which genes to be bundled up and silenced. And that's the epigenome, the reader of the genome.

• 3:40Neil deGrasse Tyson?

  Wow. But, but why is it new? I mean, it sounds like that, that should have been well.

• 3:46Chuck Nice?

  That should have always been there.

• 3:47Neil deGrasse Tyson?

  Always been known and understood.

• 3:49Chuck Nice?

  Right.

• 3:50Speaker 03

  Yeah, and it's just as important as DNA. The reason that it's not really talked about as much is it's a lot more difficult to study. It's super easy now to read a genome. You can read it on a, on a little device this big in, in less than a day. It used to be $2 billion and take months, but now it's, it's easy. But the epigenome is still hard to read because it's three dimensional and over time four dimensional, and these structures are still being elucidated.

• 4:17Neil deGrasse Tyson?

  Well, just get AI to do it all and you can go to the Bahamas while it figures it all out.

• 4:21Chuck Nice?

  Yeah, exactly.

• 4:22Speaker 03

  I tried.

• 4:22Chuck Nice?

  And it'll do it in a day.

• 4:25Neil deGrasse Tyson?

  I mean, because...

• 4:26Chuck Nice?

  The same way we read it now in a little device, it'll do it in a day, you'll come back and it'll be all done.

• 4:30Neil deGrasse Tyson?

  I have a bad analogy. I mean, I was early in the days when you programmed computers and computers, they would have the program, but how they would function while they were executing that program could be influenced by what we call dip switches. And on the back of the program, you'd lift them up or down. They're binary. So it was on or off. And depending on that configuration, your outcome would be different, even when everything else was the same. Is that a fair analogy?

• 4:57Speaker 03

  Yeah, it is. You're dating yourself for sure.

• 5:02Chuck Nice?

  Yeah. What were you programming in? Fortran? What was happening?

• 5:06Neil deGrasse Tyson?

  Oh, it's before that. Yeah. Oh, yeah. Yeah.

• 5:08Speaker 03

  I teach students that CDs are the analogy where the music is the DNA and the reader, the laser beam, but even that's outdated. But the idea of software being the epigenome is perfect. I often say that we age because our software gets corrupted. And what's exciting about the theory that I have, which is called the information theory of aging, is that we think there's a backup copy of that software that we can reboot and get an old computer, an old body to be young again.

• 5:38Neil deGrasse Tyson?

  Are you saying aging is a disease?

• 5:42Speaker 03

  I definitely think aging is a disease. In fact, even if you look up the definition of what a disease is, it's something that happens over time that makes you sick and can even kill you. If that's not aging, I don't know what is. It's only that aging is very common. And just because something is common doesn't mean we should ignore it or just regard it as natural and acceptable.

• 6:02Chuck Nice?

  Right. So have we naturally, has aging changed over a period of time, naturally? Now, we know that aging has changed because of medical technology, but that's an outside force affecting aging. Has aging changed from, say, I don't know, the 15th century to now? People died at 30 years old back then. You know, are we naturally living longer?

• 6:29Speaker 03

  Uh, yes, but not because of aging, but because of sanitary advances and, you know, good clean water and.

• 6:36Neil deGrasse Tyson?

  Yeah, Chuck, people, half the people died by thirty five up to the mid eighteen hundreds.

• 6:41Speaker 03

  Yeah.

• 6:41Neil deGrasse Tyson?

  So it changed very little from caveman up through the nineteenth century.

• 6:46Speaker 03

  Yeah.

• 6:46Neil deGrasse Tyson?

  It's all, it's all science and, and health and, and, and, and sanitation for sure. And vaccines.

• 6:52Chuck Nice?

  It took us that long, it, it took us that long to learn not to eat where we poop and to wash our hands. That's, that, that's, that's all that, that's what you tell.

• 7:01Speaker 03

  I was thinking this out and at the time, nobody believed him. They even, uh, they put the handle back on that water pump and said, it cannot be possible that poop causes disease. Uh, a few months later, they had another outbreak of cholera in London, so they, they believed him finally.

• 7:14Neil deGrasse Tyson?

  Hmm. Very, very important, David. If I remember that story, there were certain households that were fed off of one well versus another, so they were able to isolate causes and effects, uh, in, in a very, a very clean, uh, clean, a very, a clear science experiment, uh, in that case. Is that the one I'm remembering?

• 7:33Speaker 03

  It's exactly right. He triangulated and found that that was the common factor within all those houses. So he actually took the handle off the pump, but the politicians, because of the outrage, uh, put the handle back on.

• 7:45Neil deGrasse Tyson?

  Enemy of the people.

• 7:46Chuck Nice?

  Wow.

• 7:46Neil deGrasse Tyson?

  And who was this again?

• 7:47Speaker 03

  John Snow.

• 7:49Neil deGrasse Tyson?

  John Snow.

• 7:50Chuck Nice?

  Oh, my God. And, and then he started fighting white walkers.

• 7:55Neil deGrasse Tyson?

  Game of Thrones. That's a prolific guy.

• 7:58Speaker 03

  Yeah.

• 8:00Chuck Nice?

  Man, that dude could do anything.

• 8:02Gary O'Reilly?

  So David, you mentioned the information theory of aging. Um, saying it is one thing, what actually is the theory?

• 8:10Neil deGrasse Tyson?

  Oh, before you answer, is this a fringey thing that you came up with and none of your colleagues agree with, or has it become mainstream?

• 8:18Speaker 03

  Uh, it's, it's mainstream. It's not, it's not accepted by everybody, but it's, it's getting there. So, to answer Chuck's question, we're actually aging faster than we used to. Our lifestyle is so comfortable that our bodies don't fight aging. And let's talk later about ways that we can reverse that and actually

• 8:38Neil deGrasse Tyson?

  Yeah, we've got a whole segment on that.

• 8:39Speaker 03

  Teach our bodies how to fight aging. But Gary, so this information theory of aging, it's in my book Lifespan. I actually put it in my book before I published it in the scientific literature, which Neil, as you know, is very rare and probably crazy thing to do. But I did it because it took so long to publish in the scientific literature, but it's out there. And we actually published a paper a year ago in the journal Cell, which is a good journal, which was a 13-year study. It was 40-something authors, 13 years of work testing the information theory of aging. And what we did was we disrupted the software of the cells in an animal, in a mouse. We scratched the CD, as I was calling it. And what we got was predictable, which was an old mouse.

• 9:24Speaker 03

  And in every aspect, it got old. And then we reversed aspects of its aging because we have the ability to reset the software now.

• 9:30Chuck Nice?

  Okay, so now you Benjamin buttoned a mouse, is what you're saying? After you made it old, you actually reversed the process?

• 9:40Speaker 03

  Yeah, we unbuttoned, then we buttoned that mouse, yeah. But they looked really old. You can see online, there are pictures of these mice. Unfortunately, they gave their lives for humanity. They got old, they got gray, they got wrinkles, they got hunched back, they got kidney, liver disease, they got blind. And then we reversed it, which is great. It means that there probably is a backup copy, like the information theory of aging suggests.

• 10:05Gary O'Reilly?

  Is there such a thing as epigenetic inheritance?

• 10:08Speaker 03

  That's where it was discovered.

• 10:10Gary O'Reilly?

  Yeah.

• 10:11Speaker 03

  That's where it comes from. Yeah, actually, a woman, Barbara McClintock, discovered it back in the 1950s. She found that there was inheritance of certain characteristics in corn.

• 10:25Neil deGrasse Tyson?

  But if you can turn them on and off, it's kind of irrelevant that it's inherited because you can just go in and turn it off and on again. Uh, as.

• 10:34Chuck Nice?

  Yeah, but you can turn it on. See, that's the problem with if it's inherited. It means that the behavior that you're doing now could actually turn on that gene expression without, without you wanting it to. So I think I'm only going off of, I read a weird study about epigenetics and cocaine use and how it would rearrange chromatin. So chromatin remodeling because of cocaine use. And if I recall correctly, they compared it to smoking cigarettes, which also does the same, not the same thing, but does a different thing genetically.

• 11:17Chuck Nice?

  So it changes like the methylation of DNA or something like that. I don't know.

• 11:23Speaker 03

  Look, you're gonna come and work from, with me at Harvard at my lab.

• 11:27Neil deGrasse Tyson?

  Yeah, no, we need him. We need him here.

• 11:31Speaker 03

  But that is impressive. What you said is true. So chromatin is the other structures, these loops of DNA, how they bundle up, because DNA itself in every cell is six feet long, but you have to get it down into that microscopic little cell. So chromatin is that, is the bundling of the DNA and open genes, red genes, the ones that the cell needs are open chromatin and then there's closed chromatin. And aging disrupts those bundles, those bundles and those loops. And smoking accelerates those changes. A whole bunch of things do. You mentioned cocaine, but if we don't exercise, if we get obese, even stress in our lives will accelerate that process. We can measure it by looking at those chemicals which you called methylation.

• 12:12Neil deGrasse Tyson?

  So is what you're saying that something can happen in your life after you're born that'll change your genetic code such that when you have offspring, it will inherit what you acquired in your life, which sounds very Lamarckian.

• 12:29Speaker 03

  It, it does. And, and actually Lamarck was partly right that how mothers.

• 12:35Speaker 03

  Act during pregnancy can actually have a bearing on their kids. We did an experiment, I had a lab in Australia. And we fed mice and rats high fat diet. They became obese and then their offspring were more susceptible to getting fat as well. That's what we call epigenetics. And you can inherit how the DNA is not, not just the strands of DNA, but how they're structured so you can be susceptible to diseases.

• 13:00Gary O'Reilly?

  Can, can this present itself in not just like a biological state of you put on weight? But if, for instance, you were stressed and it's the mental aspect of a person's being?

• 13:12Speaker 03

  Oh, for sure. Yeah. How you behave during pregnancy can greatly affect how your kids are when they come out. So yeah, even in the womb, you can have a big effect on the future life, even the end of life of your children.

• 13:25Chuck Nice?

  Yeah, I read somewhere about mothers who did not want their children. How they, they did a study and found that that actually had a bearing on the child's mental wellbeing, the fact that the mother didn't want the child.

• 13:39Speaker 03

  That's very true. And what we're learning now is that there are ways that you can raise children and even as adults modify your lifestyle so that you can overcome these things that may affect your ability to be, you know, a healthy mental and physical human being.

• 13:55Gary O'Reilly?

  So we can actually determine how our children will be, not just by the genetics, but by, for instance, you became super fit or you increased your intelligence in some way or another, you could then pass that into your children?

• 14:12Speaker 03

  Uh, yeah, yeah, for sure. And it's these chemicals that Chuck mentioned, these methyls that probably determine how our DNA is inherited to the kids.

• 14:20Neil deGrasse Tyson?

  What does it mean to change my DNA if I have a DNA in every one of the power of many cells there are in my body? Is it changing in every one of those cells? Is it only changing in the sperm and the egg?

• 14:31Speaker 03

  So how you behave, what you eat, whether you exercise, whether you get obese, that changes the epigenetics in the whole body. So your genes are changing and how they get switched on and off. And then your children can inherit those. But the DNA sequence, the actual string of chemicals, the four letters A T C G, strung a billion times in different combinations, that doesn't change. So the reader changes, but not the actual music of the cells.

• 15:08Speaker 04

  I'm Ali Khan Hemraj and I support StarTalk on Patreon. This is StarTalk with Neil deGrasse Tyson.

• 15:23Gary O'Reilly?

  So David here, "Oh, you must have good genes. You look so young," right? And then some people age prematurely. How does that kind of balance itself out in terms of the epigenetics? Or is that just the way life goes?

• 15:37Speaker 03

  What he's asking, Dave, is how come black don't crack? That's what he's asking.

• 15:41Chuck Nice?

  There you go.

• 15:44Speaker 03

  Let me start by saying, Gary, I love you. Second of all, what I've been doing is really based on science. I've been sciencing the heck out of myself, as Matt Damon kind of said. And so I take the discoveries from my lab and the field and I apply them in my life. That's Matt Damon in the movie The Martian. That's right. Yes. Written by Andy Weir, who is a previous guest on StarTalk.

• 16:10Speaker 03

  Exactly. And so I've been sciencing myself a little bit. Doing the right things that we think stabilize the epigenome. Make sure the genes don't get switched on and off in the wrong way over time. And so if I truly am biologically young and by some tests, I'm about a decade younger than my current age, which is 54, then I've been doing the right thing so far. But ultimately, I want to be able to reset everybody's age by a few decades, every few decades.

• 16:39Chuck Nice?

  Oh, okay.

• 16:39Speaker 03

  But then we never die?

• 16:40Chuck Nice?

  This can be an ongoing process.

• 16:43Speaker 03

  It may be. I don't know of a scientific law that says we must die. I mean, eventually the universe will die and we will go along with it. But there's no biological law that says we need to age. Have you reached escape velocity? No. Right now, the velocity is that for every year we stay alive, we get an extra three months. But eventually, it'll be for every year, we'll get another year.

• 17:08Neil deGrasse Tyson?

  So that would be escape velocity.

• 17:09Speaker 03

  Correct.

• 17:09Neil deGrasse Tyson?

  And then there's the quality of life that we care about.

• 17:13Speaker 03

  Well, this is a misconception that the longer you live, the sicker you are. That's going to change. What we're doing is actually keeping people younger so that in your eighties, nineties and hundreds, you're not sick. You can still play tennis and hang out with friends.

• 17:27Chuck Nice?

  There's a great study about how diet and exercise, the two things that everybody just takes for granted because we hear it all the time, can actually keep you young well into your eighties. And a lot of it has to do with resistance training. A lot of it has to do with muscle mass, bone density and the diet that you're putting in.

• 17:49Neil deGrasse Tyson?

  But I hear all this about food, but there's so much conflicting information regarding diet. At what level will the genes show themselves? I'm leading the witness here. At what level will the genes show themselves to be predominant over so many other things that we actually think are affecting your age? Because many of the peoples who are, "I'm healthy and I do this and I do that," they die at the same age as everybody else.

• 18:16Speaker 05

  I've been smoking my entire life and I feel great. I don't understand it. My father smoked, my mother smoked. He lived until he was 87 and he had no problems at all. Of course, he only had half a lung, but who needs more than half a lung?

• 18:35Speaker 03

  That's so true, Chuck. Right, right. These anecdotes don't make science, as you know, but the...

• 18:42Neil deGrasse Tyson?

  Right, right. And I'm just wondering if at the end of the day, it's different people have different genetics and that is maybe the 900-pound gorilla in the diet room.

• 18:51Speaker 03

  Well, for sure. We're all individuals. We have different microbiomes in our guts. We have different genomes. And so how we respond to food is very different, of course. Somebody might need more vitamins. Somebody might need more protein. We tailor it, actually. Right now, we live in a world where you can actually read your genome and make decisions about what to eat and how much to exercise based on that information.

• 19:14Gary O'Reilly?

  Are we saying here that epigenetics is a cell's operating system? And you've worked out a way where you can just dial the hands on the biological clock backwards?

• 19:25Speaker 03

  Yes, exactly that. Are we done now? Yes.

• 19:29Neil deGrasse Tyson?

  No, no, no. So, let's get, let's, okay, if there's a goat in any sport, and we want them to forever stay the goat, they would just see you, and they, but we'd still have Wayne Gretzky and, and playing hockey, for example, or Michael Jordan, or, you know, or Hank Aaron's still hitting home runs.

• 19:53Speaker 03

  Very true.

• 19:54Neil deGrasse Tyson?

  Which, is this, is this, do you keep everything, is this, because it sounds like this is, none of this is true. It just sounds like it can't be true. Because we're so used to this world where aging is, like you said, something that diminishes your capacity, ultimately kills you. We, we were born living this understanding of life.

• 20:17Speaker 03

  Well, we, we used to think that about flying, right? Before the Wright brothers, it was impossible to fly, and then they did it and everything changed. The same is happening in the aging field, where what was impossible is now becoming possible. I agree, it sounds crazy to say aging is controllable, but we're doing it in my lab all the time. My students don't think anything of reversing aging by 70% in an animal or in a cell. It's commonplace, but it's not generally used across society. The closest we've come now is curing blindness in mice and monkeys, in old age and in damaged eyes. Humans will try next year, but it's, the, the theory is holding up. And if, if I'm right, then it really will be a different world, probably for us, but certainly for our children.

• 21:00Neil deGrasse Tyson?

  This is the information theory that you described.

• 21:02Speaker 03

  Information theory of aging, yeah, it's based actually on Claude Shannon's work, which you're familiar with, I'm sure, is the MIT professor who figured out how to transfer information over time and space without any losses. And he proposed the backup copy, which is, uh, that really the basis of the, the internet, the TCP IP protocol.

• 21:19Neil deGrasse Tyson?

  So if I understand what you're saying, there's the, the first copy of our genetic code that we're operating on, and that can get damaged and things can happen to that, and a lot of that ages us. You're saying, part the curtains, there's a backup copy that can restore our youth.

• 21:40Neil deGrasse Tyson?

  And so you need to get access to that backup cockpit and engage it. So that it takes over whatever was happening. On the other side of the curtain, on the front of the curtain.

• 21:50Speaker 03

  That's very well put. Actually, we used to say DNA is our destiny. That's not true for aging and longevity and health span. Only about 10 to 20% is genetically determined. The rest is this epigenetic determination. And that's behind the curtains. And so what we're, we figured out as a field, and we do this in my lab is. We can turn on genes that resets the system, that reinstalls the software. And there's a backup copy in every cell that we've discovered that it exists. Exactly where it is hidden, where it is behind the curtain, we don't know for sure. But we know it exists because we can very easily, within just a matter of a week or two. Get tissues of animals to go back by 50, 75% of their age.

• 22:33Speaker 03

  And then they don't just work well because they're like they're young again. They literally become young again.

• 22:39Chuck Nice?

  So now, why is it then that um? We find aging throughout the entire animal kingdom? I mean, we being animals, so too. But why is it that we find aging throughout, you know, the, the, the whole of the animal kingdom?

• 22:54Speaker 03

  Well, aging happens largely because of a lack of natural selection. Okay, getting back to fundamentals. Evolution works on species to allow you to reproduce and replace yourself. And as long as we live, at least in our history, on the savannas of Africa. Living to 40 or 50 was sufficient to ensure the survival of the species. And beyond that, we became expendable. And so we don't have bodies that last much longer than that, unfortunately. And often it's not worth building a body that lasts so long because you're going to be killed anyway. Right? Probably our, our ancestors were picked off by a tiger. I know tiger, a lion probably earlier than that. Or disease or starvation. But animals that are really tippy top of, of the food chain.

• 23:39Speaker 03

  Like we are now, but we, we, we weren't before where we evolved. So let's take a whale or even a bat, bats rarely preyed upon. They live a long time, considering um. Animals that they evolved from. And that's because they can afford to build a body that lasts for a long, long time. Cause they're not likely to die and they just breed a little slower. Cause they're spending some of their energy on building a long lasting body as well. Trees are probably the best example that can live for thousands of years. And and their biology is not that different than us. It's just that their epigenome, the stability of those structures that read the DNA are very stable compared to a mouse, where they basically their epigenome falls apart in a couple of years.

• 24:23Neil deGrasse Tyson?

  How about those angry trees in Wizard of Oz? Do they, how long would they live? They have anger issues.

• 24:29Speaker 03

  I think there were a lot of toxins in that, in that rubber, so.

• 24:33Gary O'Reilly?

  Let's go back. Can we go back to that point where you talked and you were quite casual about, oh, my students in the lab are quite comfortable dialing up and dialing down the age of mice. But then you said you cured blind mice. I mean, this, this is ruining a children's nursery rhyme, but.

• 24:50Neil deGrasse Tyson?

  Yes.

• 24:51Gary O'Reilly?

  I mean, how impactful are we here? So your research, was it, oh, this is great, this happened? Or was this designed to actually cure mice of their blindness?

• 25:05Speaker 03

  Well, it's a bit of both. The theory, inflation theory predicts that we should be able to rejuvenate and heal tissues in a way that only Deadpool is able to, or an axolotl that loses a limb. So that's the expectation. But when it actually happens, it's another thing. To see it happen, that was a very good day. That happened in 2017. My student sent me an image of a, of a, an optic nerve regrowing back to the brain after we reprogrammed it, made it very young. And that was a very good day in my career. That paper ended up on the cover of Nature magazine. And that was the first time that I actually thought, yeah, in our lifetime, we might be able to truly reset the age of our bodies.

• 25:44Gary O'Reilly?

  This is incredible. So when we're working with optical nerves and the axons and all the rest of it that go in, in, in the side, what at a cellular level are you, I don't want to say playing with altering to achieve these amazing results?

• 26:01Neil deGrasse Tyson?

  Yes, God.

• 26:04Speaker 03

  Well, I'm not playing God in my lab. I think what I'm playing is I'm just mimicking what embryos do and axolotls and fish do naturally.

• 26:17Neil deGrasse Tyson?

  Wait, wait Chuck. Anyone who says, "I'm not playing God in my lab," is playing God. To even be in that situation to utter that sentence.

• 26:27Chuck Nice?

  Where you have to actually deny it's playing God. Clearly, you're playing God if you have to deny it. And when you follow that statement up with, "I'm just doing what embryos do," it's like, "Come on."

• 26:46Speaker 03

  Yeah, you're right. When you put it that way. What we're doing is we're mimicking what very young animals do. And what they do is they turn on a set of genes that are like, reset genes, reprogramming genes. And the lucky thing that we discovered is that you only need three genes to reset the entire age of the animal. These three genes have names, SOX2, so O, S, and K. So this O, S, and K, three gene combination, is what we and embryos use to stay young. And when we turn these genes on again in the adult animal, whether it be a mouse or a monkey, they rejuvenate. Their tissues heal and they get young again.

• 27:30Chuck Nice?

  So can you talk about, and this may have nothing to do with what, you know, you do, however, I read about telomeres and how the longer your telomeres are, the longer you may possibly live. So what is the association there? And maybe you should tell people what telomeres are as well.

• 27:47Neil deGrasse Tyson?

  If I remember correctly, this telomeres, telomeres, that's what it's called? Yeah. That was a very important point of study for the medical analysis of the Kelly brothers, Scott Kelly and Mark Kelly, were identical twins. They sent one into orbit and left one down on Earth. And just to see if the exposure to the radiation in space and zero G and the like, would have an effect there. So does that matter in your life and what you study? Are you deeper than that?

• 28:15Speaker 03

  Yeah, so till, um, we're actually higher, not deeper in, in the hierarchy of control. But let's define telomeres. So telomeres are the ends of the chromosomes that get shorter over time. And when they get too short, then cells stop dividing. They become zombie-like and they sit there and they cause trouble. They give inflammation and cancer. So you don't want your telomeres, your chromosomes, to get too short. So telomere shortening is what we call one of the hallmarks of aging. And there are about a dozen hallmarks. There are a variety of other hallmarks, things like mitochondrial dysfunction, it's called protein misfolding, stem cells get exhausted. I won't list all 12. But what we think the, the information theory of aging, this epigenetic

• 29:00Speaker 03

  change, we think that that's at the center of all of these hallmarks. And those are manifestations. So changes to the epigenome result in telomere shortening, result in all of these other effects that give us diseases and cause aging.

• 29:14Gary O'Reilly?

  So is this OSK therapy going to be a gateway for other processes that lead us into some interesting results in general medicine?

• 29:27Speaker 03

  Well, we hope so. There's, since we published that paper in Nature in 2020, there'd been about $6 billion invested in this topic in companies that are working towards making drugs based on rejuvenation. I have, in full disclosure, a couple of companies that are working on this. One is going to be starting human trials next year to treat glaucoma and stroke at the back of the eye. But we hope that it's not just the eye. So far, it looks like the therapy works on all tissues that we've tried. In the mouse, it's muscle, liver, kidney, even brain. Age reversal works in the animal. They get smarter again. And so hopefully, this method of addressing health and disease will be

• 30:09Speaker 03

  broadly applicable. Though I don't think it's going to always be a gene therapy, because that's expensive, it's, it's hard to get the genes into the eye, let alone the body. So we're working on cheaper methods. So instead of it costing half a million dollars to cure blindness, we're working on ways to make it what cost about $10.

• 30:28Chuck Nice?

  Okay, so now what is the name of that company? And how do I get preferred stock?

• 30:47Gary O'Reilly?

  So David, are we here looking at a permanent resolution to these diseases? Or are we going to have to come back every six months and get a refill?

• 30:59Speaker 03

  Yeah, that was a key question when we first did this. How long does it last? The good news is it lasts for most of the rest of the lifespan of the mouse. The mouse ended up dying with very young eyes. And so we now know we can reset the system every six months very safely. So I think what's going to happen is you'll get cured of your glaucoma. Your eye will get young. It'll age out again and you just get a reset every decade or so. And that's how it'll work.

• 31:24Chuck Nice?

  Wow. Look at that.

• 31:26Gary O'Reilly?

  Okay, so we're talking scale here. If you're going from half a million dollars to 10 bucks, that's gonna, I mean, how long? Between now, this conversation that we're having at the beginning of 2024, to that actually being a possible reality? How long are we talking here?

• 31:43Speaker 03

  Well, where we're at is we just published in 2023, the first of chemical cocktails that reverse aging in cells. And so we started with thousands of different molecules. We're down to a couple that look really good. We in fact have engineered a single molecule that reverses aging. So that molecule, if it turns out to be safe, it could be in a pill if all goes well in about five to six years from now.

• 32:14Chuck Nice?

  And may I have the patent number on that molecule, please?

• 32:18Gary O'Reilly?

  You keep chipping away, don't you? You keep chipping away.

• 32:23Speaker 03

  Yeah, well, we also would like to put it into skincare because that's an easier application than an eyeball. We did.

• 32:31Neil deGrasse Tyson?

  That was a very big feature of the movie The Island, which was another genetic movie.

• 32:38Chuck Nice?

  I'd see it.

• 32:39Neil deGrasse Tyson?

  A big running theme there was the skin that they would harvest of a genetic copy of a person in the real world whose skin would get old. But there they would just give them a whole skin transplant. Is there? So I'm in the show me the money camp here. So if you can reverse aging. Show me the mouse that hasn't died yet because you keep pumping it full of life.

• 33:08Speaker 03

  Yeah.

• 33:09Neil deGrasse Tyson?

  And a mouse.

• 33:10Chuck Nice?

  Come on, man. How, what do you want? The guy is curing blindness. You want the mouse to live forever? You got a problem? Tell me, he's, he's, he's fricking Jesus to mice. And you got a problem with him? Come on.

• 33:27Neil deGrasse Tyson?

  Right to the blind.

• 33:30Speaker 03

  Oh, dear.

• 33:31Neil deGrasse Tyson?

  Oh, he's not full of God yet. He's just, just Jesus, the Jesus prophet level. All right. No, so here it is. So I'm asking because a mouse in the wild might live 18 months before it's consumed. It's tasty snack for, for predators. In captivity, several years. It's, have you, can you show me a 12 year old mouse, mouse? The oldest mouse there ever was? Why can't you do that now? And that would be the evidence?

• 34:01Speaker 03

  Well, in 12 years, I might have something for you. Right now, what we have is it's a paper that another group used our same technology. We gave them our gene therapy and they gave it to extremely old mice. They were 25 months old, which is like an 85 year old human. So they were almost gone and they extended the remaining life of those mice by 109%. And that's a paper that's online currently. Wow.

• 34:26Neil deGrasse Tyson?

  That's.

• 34:27Chuck Nice?

  That's, that's pretty damn impressive.

• 34:29Neil deGrasse Tyson?

  So that's doubling your life.

• 34:30Speaker 03

  Hmm.

• 34:31Chuck Nice?

  Yeah.

• 34:32Speaker 03

  It's only doubling their remaining life. So it's, it, I don't know what it was if you'd look at the whole lifespan, but it.

• 34:37Gary O'Reilly?

  I think Neil's convinced. I'm just saying by the look of Neil's face, he's not overly convinced that you just doubled their lifespan. What's more?

• 34:45Chuck Nice?

  Neil wants Methu, Neil wants Methuselah mouse. That's what he wants.

• 34:51Neil deGrasse Tyson?

  I want a wise mouse coming in.

• 34:53Chuck Nice?

  Exactly. With the cane, just and a long goat, you know?

• 34:59Gary O'Reilly?

  So I'm never going to get a chance, David, I'm never going to get a chance to say this ever again. Most, well, most unlikely that I will, but and you'll, you'll unpack this for me and make sense of the word salad. Real time nucleocytoplasmic protein compartmentalization. Please explain.

• 35:17Speaker 03

  Oh, well, that, that was one of the measurements that, that we used in the paper that discovered the chemicals that reverse aging. It's very simple. In the cell, there's the nucleus where the DNA is, and then the cytoplasm around it. And we made human cells and mouse cells have a bright red nucleus by putting a fluorescent protein from a jellyfish in there. And then we made the green cytoplasm with another different jellyfish protein. So now we have cells that are red, surrounded by green. That's a nice, young, healthy cell. As cells get older, as we grow them in the dish, then what happens is the nucleus becomes leaky. And now the red dot doesn't look as nice.

• 35:59Speaker 03

  And so we use artificial intelligence to be able to measure that in millions of cells. And it can tell us which chemicals are taking an old cell where it's got a leaky nucleus and getting it back to that original young state. And that's what we did.

• 36:13Chuck Nice?

  Wow.

• 36:14Gary O'Reilly?

  Thank you. All right. So where did the Yamunaka genes fit into this whole scenario?

• 36:21Speaker 03

  Oh, yeah, that's a good question. So Yamunaka is a very famous, deservedly so, scientist from Japan who won the Nobel Prize for discovering four genes that reset a cell to be a stem cell. So he could now turn any cell into a stem cell.

• 36:39Chuck Nice?

  Any cell into a stem cell.

• 36:40Neil deGrasse Tyson?

  Which removed from the headlines all of the concern about embryonic stem cells.

• 36:46Chuck Nice?

  Right, and you're right, because you didn't need to.

• 36:48Neil deGrasse Tyson?

  Yeah, they made it a non-story after that.

• 36:51Chuck Nice?

  Yeah, not to be confused with Yamunika, who was a very funny black comedian.

• 36:55Gary O'Reilly?

  Thank you for defining that, Chuck.

• 36:57Chuck Nice?

  No, I'm dead serious. I'm dead serious.

• 37:01Chuck Nice?

  Like, I'm not even joking.

• 37:02Speaker 03

  And the reason that those genes are relevant is that those O S and K genes are a subset of the Yamunaka genes. So we don't use the full set, because otherwise you'd go back to age zero and become a giant tumor. We use a subset of the Yamunaka genes, O S and K, and therefore it's very safe. You don't get to go back to zero. You just go back 75% of age and stop there.

• 37:24Gary O'Reilly?

  Wow. So, um, using my athletic brain, which is obviously not very bright, but it's very wealthy and I can quite easily afford a half a billion, million dollars, or whatever it is. Are there athletes out there at the moment experimenting with this sort of process to extend the bell curve of their careers?

• 37:48Chuck Nice?

  And do you want LeBron James's phone number?

• 37:51Speaker 03

  Well, some of my good friends are athletes and yeah, I can't divulge any names, but yes, athletes are paying a lot of attention to longevity science because longevity molecules, longevity medicines seem to improve your current health as well and your performance. And so it won't just be one day that we get to live longer or healthier, but we get to feel better even midlife as well.

• 38:14Chuck Nice?

  So you know, Tom Brady played for a very long time and he had one of the most incredibly unappealing diets that anybody could have. And he attributes that to his longevity in the sport and his ability to not get injured and to recover. Is diet one of the most important things you can do to extend your life if you don't have this technology available?

• 38:43Speaker 03

  Right, yeah, Tom did all the right things. He didn't eat too much, he ate less often, he didn't eat three, four meals a day, drank a lot of water, he gave a lot of massages to his muscles. All of these things trigger the body into survival mode, which is long-term very beneficial, slows down aging. And to me, it was no surprise that he continued playing till his late 40s.

• 39:09Chuck Nice?

  And survival mode is different than, you know, fight or flight mode, right? That's... You know, because a lot of people think survival, they automatically think fight or flight. So what would be the difference between survival mode and fight or flight?

• 39:24Speaker 03

  Yeah, well, fight or flight is more of a psychological stress. This is biological stress. The cells want to fight against adversity and try and survive. So when they don't have enough energy or you've been running, the cells will hunger down and preserve their health and delay aging. And these genes that we discovered, the Surtuans, they get activated by fasting and by exercise and by certain molecules from plants that, like N A D, which you can, you can take as a supplement. And so my father's been doing all those things. He's now eighty four in literally perfect health. So he's a beacon of hope. He's not a clinical trial, but hopefully one day, most people can live till their mid eighties and still be just as healthy as they were in their forties.

• 40:05Gary O'Reilly?

  So we're talking about things that do us good. What's the, the criminal lineup for the worst foods we could put in our systems?

• 40:14Speaker 03

  Ah.

• 40:15Chuck Nice?

  Anything you find in America.

• 40:17Speaker 03

  Well, yeah, it's what you eat and when you eat. We overeat, we eat too often, and we also eat things that are just too many calories. So sugar is the biggest culprit. A lot of fat. I try to avoid meat. So there are a lot of people who love meat. There's no evidence that a lot of meat extends your lifespan. In fact, a lot of the contrary. So yeah, those are the main things. And avoiding fresh foods is the problem in this country. We eat a lot of processed, highly processed foods, canned foods. These are not good because the the wonderful molecules that slow aging have been destroyed when you cook them.

• 40:56Chuck Nice?

  Hmm. Wow. So raw vegan. Ech. That's the life. Ech. I can't believe it.

• 41:04Neil deGrasse Tyson?

  Um, there are some vitamins and nutrients that are in raw vegetables that you cannot digest through the fiber to get to them. So that there's an ideal cook time so that you can actually access them. Oh, yeah.

• 41:17Speaker 03

  That's correct.

• 41:17Neil deGrasse Tyson?

  So.

• 41:18Chuck Nice?

  That's true.

• 41:18Neil deGrasse Tyson?

  Not overcooked and not undercooked.

• 41:19Chuck Nice?

  They say you blanch it.

• 41:20Neil deGrasse Tyson?

  Right.

• 41:21Chuck Nice?

  Yeah, they say you blanch kale because otherwise you're just passing it through your system. It's not doing anything for you.

• 41:27Speaker 03

  Yeah, well, my, my partner put me on to this stuff, which is green tea matcha, which is they stress the green tea leaves before they harvest and they're full of all of these wonderful molecules as well.

• 41:37Gary O'Reilly?

  Chuck, they just stand there and shout at them. They're abusive.

• 41:43Speaker 03

  Exactly.

• 41:44Chuck Nice?

  Green tea.

• 41:44Speaker 03

  So look for colorful vegetables. Uh, my partner Serena says eat the rainbow. That's a good start.

• 41:50Gary O'Reilly?

  Interesting.

• 41:51Chuck Nice?

  Okay.

• 41:51Speaker 03

  But not, is, but not those candies that are rainbow, the plants that are colorful.

• 41:55Chuck Nice?

  No, that's Skittles.

• 41:56Gary O'Reilly?

  That take, you're taking away all the fun, David. Um, we're heading towards medicine that is bespoke for the individual. Are we going to get to a point where gene therapy will not work for certain individuals? Or is this is going to work for whoever?

• 42:11Speaker 03

  Well, given that it's working in, in dogs and in, in mice, it's probably going to work in people, I would, I would imagine. It's working monkeys as well. So I, I'm not so worried about that. I think this is a universal system, but we are entering a world where we can tailor the way we exercise, what we eat individually, right? We all have different microbiomes. We have different gut lining, we have different genomes and we can measure that now. The big revolution besides what I'm talking about in my lab is actually the ability to measure our bodies a thousand times a second and detect a disease before it would show up, even sometimes five, 10 years later. And that, I think that cancer, heart disease and diabetes are largely preventable diseases

• 42:55Speaker 03

  right now with today's technology.

• 42:57Neil deGrasse Tyson?

  Well, we look forward to this transforming the landscape. I can tell you that if we all live forever, we need another planet.

• 43:02Speaker 03

  That is, that's very true, but I'll leave that one up to you and Elon to figure out.

• 43:07Neil deGrasse Tyson?

  Yeah.

• 43:10Neil deGrasse Tyson?

  Yeah, we're coasting into 10 billion people and that's only if no one lives significantly longer than they currently do.

• 43:16Speaker 03

  Yeah.

• 43:16Neil deGrasse Tyson?

  We could probably sustain 10 billion, but not 50 billion or a hundred billion. So keep it going. Delighted to get you for this session and we'd like to check back in on you, maybe in a year or two, to find out.

• 43:28Chuck Nice?

  Or maybe 200 years, who knows?

• 43:30Neil deGrasse Tyson?

  You're going to show me that 10 year old mouse. That's what you're going to show me.

• 43:33Speaker 03

  Yeah, or hopefully I can show you a, a person that's been cured of blindness. That would be great if that.

• 43:39Neil deGrasse Tyson?

  Wouldn't that be great?

• 43:41Speaker 03

  Yeah.

• 43:41Neil deGrasse Tyson?

  Ooh. Oh, yeah. Yeah, yeah. Okay, this has been another installment of Startalk Special Edition. The epigenome and aging, long overdue topic. Neil deGrasse Tyson here, your personal astrophysicist. As always, keep working out.