SPEAKER_1: 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.
SPEAKER_1: This is a future that may be closer than you think.
SPEAKER_1: Welcome to StarTalk, your place in the universe where science and pop culture collide.
SPEAKER_1: StarTalk begins right now.
SPEAKER_1: This is StarTalk's special edition.
SPEAKER_1: Neil deGrasse Tyson here, your personal astrophysicist.
SPEAKER_1: Got with me my usual band of co-hosts, Gary O'Reilly, Gary.
SPEAKER_2: Good to be here.
SPEAKER_1: All right, former soccer pro, sports commentator, and Chuck Nice, Chuck, my favorite stand-up comedian.
SPEAKER_1: How are you doing, Chuck?
SPEAKER_3: You can call me Friar Chuck since we're a band of married men now.
SPEAKER_1: As we frolick along the countryside, yeah.
SPEAKER_1: Today's topic is epigenetics.
SPEAKER_2: Yeah.
SPEAKER_1: We're long overdue for fielding this subject.
SPEAKER_1: And of course, we do what we normally do in StarTalk, is comb the landscape, looking for the particular expertise we seek.
SPEAKER_1: And let's find out in a moment who that is.
SPEAKER_1: But Gary, tell us how you and your producers came up with this idea.
SPEAKER_2: Robin Hood and I sat down with the band of Merry Men, with something we've been interested in doing.
SPEAKER_2: And it's one of those things that's hiding, if you like, in plain sight again.
SPEAKER_2: But it is a fast emerging subject that we needed to get a handle on.
SPEAKER_2: Can we defy the march of time as our only hope of looking young and being younger?
SPEAKER_2: A facelift.
SPEAKER_2: Could we in fact dial up or even dial down our own body's aging process?
SPEAKER_2: This is actually a really seriously heavy question, and it's expert time.
SPEAKER_2: So, Neil, if you would like to introduce our guest.
SPEAKER_1: So, this is a former Time 100 awardee.
SPEAKER_1: 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.
SPEAKER_1: Professor David Sinclair.
SPEAKER_1: David, welcome to StarTalk.
SPEAKER_4: Hey, thanks for having me on.
SPEAKER_4: Good to see you again, Neil.
SPEAKER_1: Again.
SPEAKER_1: Yeah, I guess we bumped into each other at the Time 100 dinner.
SPEAKER_1: They bring back an old timer.
SPEAKER_3: I'm sorry I missed you guys.
SPEAKER_3: I'm so sorry I missed you.
SPEAKER_3: Yeah.
SPEAKER_3: I don't know what happened.
SPEAKER_3: I don't know why we didn't see each other.
SPEAKER_1: You're a 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.
SPEAKER_1: So first of all, let's get some groundwork here.
SPEAKER_1: What is—we've all heard of genetics, but what is epigenetics?
SPEAKER_1: And the only—epi—I think of epi-pen and I think of epi-center of an earthquake.
SPEAKER_1: So how do you get epigenetics out of that word?
SPEAKER_4: Yeah, well, it's similar to the center of an earthquake.
SPEAKER_4: There are two types of information in the body.
SPEAKER_4: We know of genetics.
SPEAKER_4: Genetics is the DNA.
SPEAKER_4: The epigenetics are the control systems that tell which genes to be switched on and off, which DNA to be looped out and unraveled and read by the cell versus which genes to be bundled up and silenced.
SPEAKER_4: And that's the epigenome, the reader of the genome.
SPEAKER_1: Wow.
SPEAKER_1: But why is it new?
SPEAKER_1: I mean, it sounds like that should have been well— That should have always been there.
SPEAKER_1: Always been known and understood.
SPEAKER_3: Right.
SPEAKER_4: Yeah, and it's just as important as DNA.
SPEAKER_4: The reason that it's not really talked about as much is it's a lot more difficult to study.
SPEAKER_4: It's super easy now to read a genome.
SPEAKER_4: You can read it on a little device this big in less than a day.
SPEAKER_4: It used to be $2 billion and take months, but now it's easy.
SPEAKER_4: 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.
SPEAKER_1: Well, just get AI to do it all, and you can go to the Bahamas while he figures it all out.
SPEAKER_3: The same way we read it now on a little device.
SPEAKER_3: It'll do it in a day.
SPEAKER_3: You'll come back.
SPEAKER_3: It'll be all done.
SPEAKER_1: I have a bad analogy.
SPEAKER_1: 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.
SPEAKER_1: They were binary, so it was on or off, and depending on that configuration, your outcome would be different, even when everything else was the same.
SPEAKER_1: Is that a fair analogy?
SPEAKER_4: Yeah, it is.
SPEAKER_4: You're dating yourself for sure.
SPEAKER_3: What were you programming in?
SPEAKER_3: Fortran?
SPEAKER_3: What was happening?
SPEAKER_1: Before that, yeah, oh yeah.
SPEAKER_4: I teach students that CDs are the analogy, whether 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.
SPEAKER_4: 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.
SPEAKER_1: Are you saying aging is a disease?
SPEAKER_4: I definitely think aging is a disease.
SPEAKER_4: 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.
SPEAKER_4: If that's not aging, I don't know what is.
SPEAKER_4: It's only that aging is very common.
SPEAKER_4: And just because something is common doesn't mean we should ignore it or just regard it as natural and acceptable.
SPEAKER_3: So have we, naturally, has aging changed over a period of time?
SPEAKER_3: Naturally.
SPEAKER_3: Now, we know that aging has changed because of medical technology, but that's an outside force affecting aging.
SPEAKER_3: Has aging changed from, say, I don't know, the 15th century to now?
SPEAKER_3: People died at 30 years old back then.
SPEAKER_3: You know, are we naturally living longer?
SPEAKER_4: Yes, but not because of aging, but because of sanitary advances and clean water.
SPEAKER_1: Yeah, Chuck, people, half the people died by 35 up to the mid 1800s.
SPEAKER_1: So it changed very little from caveman up through the 19th century.
SPEAKER_1: It's all science and health and sanitation for sure.
SPEAKER_3: And vaccines, yeah.
SPEAKER_3: It took us that long to learn not to eat where we poop and to wash our hands.
SPEAKER_3: That's what you're telling me.
SPEAKER_4: At the time, nobody believed him.
SPEAKER_4: They put the handle back on that water pump and said, it cannot be possible that poop causes disease.
SPEAKER_4: A few months later, they had another outbreak of cholera in London, so they believed him finally.
SPEAKER_1: Very important, David.
SPEAKER_1: 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 in a very clear science experiment in that case.
SPEAKER_1: Is that the one I'm remembering?
SPEAKER_4: It's exactly right.
SPEAKER_4: He triangulated and found that that was the common factor within all those houses.
SPEAKER_4: So he actually took the handle off the pump, but the politicians, because of the outrage, put the handle back on.
SPEAKER_1: Enemy of the people.
SPEAKER_1: And who was this again?
SPEAKER_4: Jon Snow.
SPEAKER_1: Jon Snow.
SPEAKER_3: Oh my God.
SPEAKER_3: And then he started fighting white walkers.
SPEAKER_2: He came around.
SPEAKER_1: He's a prolific guy.
SPEAKER_2: Yeah.
SPEAKER_3: Man, that dude could do anything.
SPEAKER_2: So David, you mentioned the Information Theory of Aging.
SPEAKER_2: Saying it is one thing, what actually is the theory?
SPEAKER_1: Before you answer, is this a fringy thing that you came up with and none of your colleagues agree with, or has it become mainstream?
SPEAKER_4: It's mainstream.
SPEAKER_4: It's not accepted by everybody, but it's getting there.
SPEAKER_4: To answer Chuck's question, we're actually aging faster than we used to.
SPEAKER_4: Our lifestyle is so comfortable that our bodies don't fight aging.
SPEAKER_4: And let's talk later about ways that we can reverse that and actually...
SPEAKER_1: Yeah, we've got a whole segment on that.
SPEAKER_4: How bodies, how to fight aging.
SPEAKER_4: 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.
SPEAKER_4: But I did it because it took so long to publish in the scientific literature, but it's out there.
SPEAKER_4: And we actually published a paper a year ago in the journal Cell, which is a good journal, which was a 13-year study.
SPEAKER_4: It was 40-something authors, 13 years of work, testing the information theory of aging.
SPEAKER_4: And what we did was we disrupted the software of the cells in an animal, in a mouse.
SPEAKER_4: We scratched the CD, as I was calling it.
SPEAKER_4: And what we got was predictable, which was an old mouse.
SPEAKER_4: And in every aspect, it got old.
SPEAKER_4: And then we reversed aspects of its aging because we have the ability to reset software now.
SPEAKER_3: Okay, so now you Benjamin buttoned a mouse, is what you're saying?
SPEAKER_3: After you made it old, you actually reversed the process?
SPEAKER_4: Yeah, we unbuttoned, then we buttoned that mouse, yeah.
SPEAKER_4: They looked really old.
SPEAKER_4: You can see online there are pictures of these mice.
SPEAKER_4: Unfortunately, they gave their lives for humanity.
SPEAKER_4: They got old, they got gray, they got wrinkles, they got hunchback, they got kidney, liver disease, they got blind.
SPEAKER_4: And then we reversed it, which is great.
SPEAKER_4: It means that it probably is a backup copy, like the Information Theory of Aging suggests.
SPEAKER_2: Is there such a thing as epigenetic inheritance?
SPEAKER_4: That's where it was discovered.
SPEAKER_4: That's where it comes from.
SPEAKER_4: Actually, a woman, Barbara McClintock, discovered it back in the 1950s.
SPEAKER_4: She found that there was inheritance of certain characteristics in corn.
SPEAKER_1: 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.
SPEAKER_1: Yeah, but you can turn it on.
SPEAKER_3: 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 you wanting it to.
SPEAKER_3: So, I think I'm only going off of...
SPEAKER_3: I read a weird study about epigenetics and cocaine use and how it would rearrange chromatin.
SPEAKER_3: So, chromatin remodeling because of cocaine use.
SPEAKER_3: And if I recall correctly, they compared it to smoking cigarettes, which also does the same...
SPEAKER_3: Not the same thing, but does a different thing genetically.
SPEAKER_3: So, it changes like the methylation of DNA or something like that.
SPEAKER_4: Chuck, you're going to come and work with me at Harvard at my lab.
SPEAKER_1: No, we need him here.
SPEAKER_4: What you said is true.
SPEAKER_4: So, chromatin is the other structures, these loops of DNA, how they bundle up.
SPEAKER_4: Because DNA itself in every cell is six feet long, but you have to get it down into that microscopic little cell.
SPEAKER_4: So, chromatin 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.
SPEAKER_4: And aging disrupts those bundles and those loops, and smoking accelerates those changes.
SPEAKER_4: A whole bunch of things do.
SPEAKER_4: You mentioned cocaine, but if we don't exercise, if we get obese, even stress in our lives will accelerate that process.
SPEAKER_4: We can measure it by looking at those chemicals, which you called methylation.
SPEAKER_1: So is what you're saying that something can happen in your life after you're born that will change your genetic code such that when you have offspring, it will inherit what you acquired in your life, which sounds very Lamarckian.
SPEAKER_4: It does, and actually Lamarck was partly right that how mothers act during pregnancy can actually have a bearing on their kids.
SPEAKER_4: We did an experiment, I had a lab in Australia, and we fed mice and rats high-fat diet.
SPEAKER_4: They became obese, and then their offspring were more susceptible to getting fat as well.
SPEAKER_4: That's what we call epigenetics.
SPEAKER_4: And you can inherit how the DNA is not just the strands of DNA, but how they're structured so you can be susceptible to diseases.
SPEAKER_2: 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?
SPEAKER_4: Oh, for sure.
SPEAKER_4: Yeah, how you behave during pregnancy can greatly affect how your kids are when they come out.
SPEAKER_4: So, yeah, even in the womb, you can have a big effect on the future life, even the end of life of your children.
SPEAKER_3: Yeah, I read somewhere about mothers who did not want their children, how they did a study and found that that actually had a bearing on the child's mental well-being, the fact that the mother didn't want the child.
SPEAKER_4: That's very true.
SPEAKER_4: 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 a healthy mental and physical human being.
SPEAKER_2: 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.
SPEAKER_2: You could then pass that into your children.
SPEAKER_4: Yeah, for sure.
SPEAKER_4: And it's these chemicals that Chuck mentioned, these methyls that partly determine how our DNA is inherited to the kids.
SPEAKER_1: 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?
SPEAKER_1: Is it changing in every one of those cells?
SPEAKER_1: Is it only changing in the sperm and the egg?
SPEAKER_4: So, how you behave, what you eat, whether you exercise, whether you get obese, that changes the epigenetics in the whole body.
SPEAKER_4: So, your genes are changing and how they get switched on and off, and then your children can inherit those.
SPEAKER_4: 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.
SPEAKER_4: So the reader changes, but not the actual music of the cells.
SPEAKER_5: I am Olicon Hemraj, and I support StarTalk on Patreon.
SPEAKER_5: This is StarTalk with Neil deGrasse Tyson.
SPEAKER_2: So, David, here, oh, you must have good genes, you look so young, right?
SPEAKER_2: And then some people age prematurely.
SPEAKER_2: How does that kind of balance itself out in terms of the epigenetics, or is that just the way life goes?
SPEAKER_1: What he's asking, David, is how come black don't crack?
SPEAKER_1: That's what he's asking.
SPEAKER_3: There you go.
SPEAKER_1: It's really what he's asking.
SPEAKER_4: Let me start by saying, Gary, I love you.
SPEAKER_4: Second of all, what I've been doing is really based on science.
SPEAKER_4: I've been science-ing the heck out of myself, as Matt Damon kind of said.
SPEAKER_4: And so I take the discoveries from my lab in the field, and I apply them in my life.
SPEAKER_1: That's Matt Damon in the movie, The Martian.
SPEAKER_4: That's right, yes.
SPEAKER_4: Plug your...
SPEAKER_1: Written by Andy Weir, who is a previous guest on StarTalk.
SPEAKER_4: Exactly.
SPEAKER_4: And so I've been science-ing 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.
SPEAKER_4: 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 things so far.
SPEAKER_4: But ultimately I want to be able to reset everybody's age by a few decades, every few decades.
SPEAKER_3: Oh, okay.
SPEAKER_1: So then we never die?
SPEAKER_3: This can be an ongoing process.
SPEAKER_4: I don't know of a scientific law that says we must die.
SPEAKER_4: I mean, eventually the universe will die and we will go along with it.
SPEAKER_4: But there's no biological law that says we need to age.
SPEAKER_1: Have you reached escape velocity?
SPEAKER_4: No.
SPEAKER_4: Right now the velocity is that for every year we stay alive, we get an extra three months.
SPEAKER_4: But eventually it'll be for every year, we'll get another year.
SPEAKER_1: So that would be escape velocity.
SPEAKER_4: Correct.
SPEAKER_1: And then there's the quality of life that we care about.
SPEAKER_4: Well, this is a misconception that the longer you live, the sicker you are.
SPEAKER_4: That's going to change.
SPEAKER_4: What we're doing is actually keeping people younger so that in your 80s, 90s and 100s, you're not sick.
SPEAKER_4: You can still play tennis and hang out with them.
SPEAKER_3: 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 80s.
SPEAKER_3: And a lot of it has to do with resistance training.
SPEAKER_3: A lot of it has to do with muscle mass, bone density, and the diet that you're putting in.
SPEAKER_1: Well, David, I hear all this about food, but there's so much conflicting information regarding diet.
SPEAKER_1: 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?
SPEAKER_1: Because many of the people who are, I'm healthy and I do this and I do that, they die at the same age as everybody else.
SPEAKER_3: I've been smoking my entire life and I feel great.
SPEAKER_3: I don't understand it.
SPEAKER_3: My father smoked, my mother smoked, he lived until he was 87 and he had no problems at all.
SPEAKER_3: Of course he only had half a lung, but who needs more than half a lung?
SPEAKER_4: That's so true, Chuck.
SPEAKER_4: Right, right.
SPEAKER_4: These anecdotes don't make science as you know, but the...
SPEAKER_1: Right, right, and I'm just wondering if at the end of the day, different people have different genetics and that is maybe the 900-pound gorilla in the diet room.
SPEAKER_4: Well, for sure.
SPEAKER_4: 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.
SPEAKER_4: Somebody might need more vitamins, somebody might need more protein.
SPEAKER_4: We tailor it actually.
SPEAKER_4: 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.
SPEAKER_2: Are we saying here that epigenetics is a cell's operating system?
SPEAKER_2: And you've worked out a way where you can just dial the hands on the biological clock backwards?
SPEAKER_4: Yes, exactly that.
SPEAKER_4: Are we done now?
SPEAKER_2: Yes!
SPEAKER_1: No, no, no.
SPEAKER_3: So, let's get...
SPEAKER_1: Okay, if there's a goat in any sport and we want them to forever stay the goat, they would just see you, but we'd still have Wayne Greske playing hockey, for example, or Michael Jordan, or Hank Aaron still hitting home runs.
SPEAKER_1: Do you keep everything...
SPEAKER_1: It sounds like none of this is true.
SPEAKER_1: 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.
SPEAKER_1: We were born living this understanding of life.
SPEAKER_4: Well, we used to think that about flying, right?
SPEAKER_4: Before the Wright brothers, it was impossible to fly, and then they did it and everything changed.
SPEAKER_4: The same is happening in the aging field, where what was impossible is now becoming possible.
SPEAKER_4: I agree, it sounds crazy to say aging is controllable, but we're doing it in my life all the time.
SPEAKER_4: My students don't think anything of reversing aging by 70% in an animal or in a cell.
SPEAKER_4: It's commonplace, but it's not generally used across society.
SPEAKER_4: The closest we've come now is curing blindness in mice and monkeys, in old age and in damaged eyes.
SPEAKER_4: Humans will try next year, but the theory is holding up, and if I'm right, then it really will be a different world, probably for us, but certainly for our children.
SPEAKER_1: This is the information theory that you described.
SPEAKER_4: Information Theory of Aging, yeah.
SPEAKER_4: 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 really the basis of the internet, the TCPIP protocol.
SPEAKER_1: So if I understand what you're saying, there's 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.
SPEAKER_1: You're saying, park the curtains, there's a backup copy that can restore our use.
SPEAKER_1: And so you need to get access to that backup copy and engage it so that it takes over whatever was happening on the other side of the curtain, on the front of the curtain.
SPEAKER_4: That's very well put.
SPEAKER_4: Actually, we used to say DNA is our destiny.
SPEAKER_4: That's not true for aging and longevity and health span.
SPEAKER_4: Only about 10 to 20% is genetically determined.
SPEAKER_4: The rest is this epigenetic determination.
SPEAKER_4: And that's behind the curtains.
SPEAKER_4: And so what we've 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.
SPEAKER_4: And there's a backup copy in every cell that we've discovered that it exists.
SPEAKER_4: 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.
SPEAKER_4: And then they don't just work well because they're like they're young again, they literally become young again.
SPEAKER_3: So now why is it then that we find aging throughout the entire animal kingdom?
SPEAKER_3: I mean, we being animals are too, but why is it that we find aging throughout the whole of the animal kingdom?
SPEAKER_4: Well, aging happens largely because of a lack of natural selection, okay?
SPEAKER_4: Getting back to fundamentals, evolution works on species to allow you to reproduce and replace yourself.
SPEAKER_4: 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.
SPEAKER_4: And beyond that, we became expendable.
SPEAKER_4: And so we don't have bodies that last much longer than that, unfortunately.
SPEAKER_4: And often it's not worth building a body that lasts so long because you're going to be killed anyway, right?
SPEAKER_4: Probably our ancestors were picked off by a tiger, I'm not a tiger, a lion probably earlier than that, or disease or starvation.
SPEAKER_4: But animals that are really tippy top of the food chain, like we are now, but we weren't before where we evolved.
SPEAKER_4: So let's take a whale or even a bat, bats rarely preyed upon.
SPEAKER_4: They live a long time considering animals that they evolved from.
SPEAKER_4: And that's because they can afford to build a body that lasts for a long, long time because they're not likely to die.
SPEAKER_4: And they just breed a little slower because they're spending some of their energy on building a long lasting body as well.
SPEAKER_4: Trees are probably the best example that can live for thousands of years.
SPEAKER_4: And their biology is not that different than us.
SPEAKER_4: 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.
SPEAKER_1: How about those angry trees in Wizard of Oz?
SPEAKER_1: They have anger issues.
SPEAKER_4: I think there are a lot of toxins in that rubber.
SPEAKER_4: So, they can wash that off.
SPEAKER_2: Let's go back.
SPEAKER_2: 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.
SPEAKER_2: But then you said you cured blind mice.
SPEAKER_2: I mean, this is ruining a children's nursery rhyme.
SPEAKER_2: But, I mean, how impactful are we here?
SPEAKER_2: So your research, was it, oh, this is great, this happened, or was this designed to actually cure mice of their blindness?
SPEAKER_4: Well, it's a bit of both.
SPEAKER_4: 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.
SPEAKER_4: So that's the expectation.
SPEAKER_4: But when it actually happens, it's another thing.
SPEAKER_4: To see it happen, that was a very good day.
SPEAKER_4: That happened in 2017.
SPEAKER_4: My student sent me an image of an optic nerve regrowing back to the brain after we reprogrammed it, made it very young.
SPEAKER_4: And that was a very good day in my career.
SPEAKER_4: That paper ended up on the cover of Nature magazine.
SPEAKER_4: 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.
SPEAKER_3: This is incredible.
SPEAKER_2: So, when we're working with optical nerves and the axons and all the rest of it that go in the side, what at a cellular level are you, I don't want to say playing with, altering to achieve these amazing results?
SPEAKER_1: Yes, God.
SPEAKER_4: Well, I'm not playing God in my life.
SPEAKER_4: I think what I'm playing is I'm just mimicking what embryos do and axolotls and fish do naturally.
SPEAKER_1: Chuck, anyone who says I'm not playing God in my lab is playing God.
SPEAKER_1: To even be in that situation to utter that sentence.
SPEAKER_3: Where you have to actually deny playing God.
SPEAKER_3: Clearly, you're playing God if you have to deny it.
SPEAKER_3: And when you follow that statement up with, I'm just doing what embryos do.
SPEAKER_3: It's like, come on.
SPEAKER_4: Yeah, you're right.
SPEAKER_4: When you put it that way.
SPEAKER_4: What we're doing is we're mimicking what very young animals do.
SPEAKER_4: And what they do is they turn on a set of genes that are like reset genes, reprogramming genes.
SPEAKER_4: And the lucky thing that we discovered is that you only need three genes to reset the entire age of the animal.
SPEAKER_4: These three genes have names, SOX2, so O, S, and K.
SPEAKER_4: So this O, S, and K three-gene combination is what we and embryos use to stay young.
SPEAKER_4: 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.
SPEAKER_3: So can you talk about, and this may have nothing to do with what, you know, you do.
SPEAKER_3: However, I read about telomeres and how the longer your telomeres are, the longer you may possibly live.
SPEAKER_3: So what is the association there?
SPEAKER_3: And maybe you should tell people what telomeres are as well.
SPEAKER_1: If I remember correctly, this telomeres?
SPEAKER_1: Telomeres, is that what it's called?
SPEAKER_1: Yeah.
SPEAKER_1: That was a very important point of study for the medical analysis of the Kelly brothers, Scott Kelly and Mark Kelly, who are identical twins.
SPEAKER_1: They sent one into orbit and left one down on Earth.
SPEAKER_1: And just to see if the exposure to the radiation in space and zero G and the like would have an effect there.
SPEAKER_1: So does that matter in your life and what you study?
SPEAKER_1: Or are you deeper than that?
SPEAKER_4: Yes.
SPEAKER_4: So telomeres, we're actually higher, not deeper, in the hierarchy of control.
SPEAKER_4: But let's define telomeres.
SPEAKER_4: So telomeres are the ends of the chromosomes that get shorter over time.
SPEAKER_4: And when they get too short, then cells stop dividing.
SPEAKER_4: They become zombie-like and they sit there and they cause trouble.
SPEAKER_4: They get inflammation and cancer.
SPEAKER_4: So you don't want your telomeres, your chromosomes, to get too short.
SPEAKER_4: So telomere shortening is what we call one of the hallmarks of aging.
SPEAKER_4: And there are about a dozen hallmarks.
SPEAKER_4: There are a variety of other hallmarks, things like mitochondrial dysfunction, it's called protein misfolding, stem cells get exhausted.
SPEAKER_4: I won't list all 12.
SPEAKER_4: But what we think the information theory of aging, this epigenetic change, we think that that's at the center of all of these hallmarks.
SPEAKER_4: And those are manifestations.
SPEAKER_4: So changes to the epigenome result in telomere shortening, result in all of these other effects that give us diseases and cause aging.
SPEAKER_2: So is this OSK therapy going to be a gateway for other processes that lead us into some interesting results in general medicine?
SPEAKER_4: Well, we hope so.
SPEAKER_4: Since we published that paper in Nature in 2020, there have been about $6 billion invested in this topic, in companies that are working towards making drugs based on rejuvenation.
SPEAKER_4: I have, in full disclosure, a couple of companies that are working on this.
SPEAKER_4: One is going to be starting human trials next year to treat glaucoma and stroke at the back of the eye.
SPEAKER_4: But we hope that it's not just the eye.
SPEAKER_4: So far, it looks like the therapy works on all tissues that we've tried.
SPEAKER_4: In the mouse, it's muscle, liver, kidney, even brain.
SPEAKER_4: Age reversal works in the animal.
SPEAKER_4: They get smarter again.
SPEAKER_4: So hopefully, this method of addressing health and disease will be broadly applicable.
SPEAKER_4: Though I don't think it's going to always be a gene therapy because that's expensive.
SPEAKER_4: It's hard to get the genes into the eye, let alone the body.
SPEAKER_4: So we're working on cheaper methods.
SPEAKER_4: So instead of it costing half a million dollars to cure blindness, we're working on ways to make it cost about $10.
SPEAKER_3: Okay, so now what is the name of that company and how do I get preferred stock?
SPEAKER_2: 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?
SPEAKER_4: Yeah, that was a key question when we first did this.
SPEAKER_4: How long does it last?
SPEAKER_4: The good news is it lasts for most of the rest of the lifespan of the mouse.
SPEAKER_4: The mouse ended up dying with very young eyes.
SPEAKER_4: And so we now know we can reset the system every six months very safely.
SPEAKER_4: So I think what's going to happen is, you'll get cured of your glaucoma, your eye will get young.
SPEAKER_4: It'll age out again and you just get a reset every decade or so and that's how it'll work.
SPEAKER_3: Wow, look at that.
SPEAKER_2: Okay, so we're talking scale here.
SPEAKER_2: If you're going from half a million dollars to 10 bucks, that's gonna, I mean, how long?
SPEAKER_2: Between now, this conversation that we're having in the beginning of 2024, to that actually being a possible reality, how long are we talking here?
SPEAKER_4: Well, where we're at is we just published in 2023, the first of chemical cocktails that reverse aging in cells.
SPEAKER_4: And so we started with thousands of different molecules.
SPEAKER_4: We're down to a couple that look really good.
SPEAKER_4: We in fact have engineered a single molecule that reverses aging.
SPEAKER_4: So that molecule, if it turns out to be safe, it could be an appeal if all goes well in about five to six years from now.
SPEAKER_3: And may I have the patent number on that molecule, please?
SPEAKER_2: You keep chipping away, don't you?
SPEAKER_4: Well, we also would like to put it into skincare because that's an easier application than an eyeball.
SPEAKER_4: We did...
SPEAKER_1: That was a very big feature of the movie The Island, which was another genetic movie.
SPEAKER_1: And 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.
SPEAKER_1: Is there...
SPEAKER_1: So I'm in the show me the money camp here.
SPEAKER_1: So if you can reverse aging, show me the mouse that hasn't died yet because you keep pumping it full of life.
SPEAKER_1: Yeah.
SPEAKER_3: Come on, man.
SPEAKER_3: What do you want?
SPEAKER_3: The guy is curing blindness.
SPEAKER_3: You want the mouse to live forever?
SPEAKER_3: You got a problem?
SPEAKER_3: He's freaking Jesus to mice.
SPEAKER_3: And you got a problem with him?
SPEAKER_3: Come on.
SPEAKER_1: Psych to the blind.
SPEAKER_1: It's just Jesus, the Jesus prophet level.
SPEAKER_1: So here it is.
SPEAKER_1: So I'm asking because a mouse in the wild might live 18 months before it's consumed.
SPEAKER_1: It's a tasty snack for predators.
SPEAKER_1: In captivity, several years.
SPEAKER_1: Can you show me a 12-year-old mouse?
SPEAKER_1: The oldest mouse there ever was?
SPEAKER_1: Why can't you do that now?
SPEAKER_1: And that would be the evidence?
SPEAKER_4: Well, in 12 years, I might have something for you.
SPEAKER_4: Right now, what we have is a paper that another group used our same technology.
SPEAKER_4: We gave them our gene therapy.
SPEAKER_4: And they gave it to extremely old mice.
SPEAKER_4: They were 25 months old, which is like an 85-year-old human.
SPEAKER_4: So they were almost gone.
SPEAKER_4: And they extended the remaining life of those mice by 109%.
SPEAKER_4: And that's a paper that's online currently.
SPEAKER_3: That's pretty damn impressive.
SPEAKER_4: It's only doubling their remaining life.
SPEAKER_4: So I don't know what it was if you'd look at the whole lifespan.
SPEAKER_2: But I'm just saying by the look of Neil's face, he's not overly convinced that you just doubled their life span.
SPEAKER_3: What's more?
SPEAKER_3: Neil wants Methuselah mouse.
SPEAKER_3: That's what he wants.
SPEAKER_1: I want an old wise mouse coming in.
SPEAKER_3: With a cane and a long goat, you know.
SPEAKER_2: So I'm never going to get a chance, David, I'm never going to get a chance to say this ever again, most unlikely that I will.
SPEAKER_2: And you'll unpack this for me and make sense of the word salad.
SPEAKER_2: Real-time nucleocytoplasmic protein compartmentalization.
SPEAKER_2: Please explain.
SPEAKER_4: Oh, well that was one of the measurements that we used in the paper that discovered the chemicals that reverse aging.
SPEAKER_4: It's very simple.
SPEAKER_4: In the cell, there's the nucleus where the DNA is, and then the cytoplasm around it.
SPEAKER_4: And we made human cells and mouse cells have a bright red nucleus by putting a fluorescent protein from a jellyfish in there.
SPEAKER_4: And then we made the green cytoplasm with another different jellyfish protein.
SPEAKER_4: So now we have cells that are red surrounded by green.
SPEAKER_4: That's a nice, young, healthy cell.
SPEAKER_4: As cells get older, as we grow them in the dish, then what happens is the nucleus becomes leaky.
SPEAKER_4: And now the red dot doesn't look as nice.
SPEAKER_4: And so we use artificial intelligence to be able to measure that in millions of cells.
SPEAKER_4: 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.
SPEAKER_4: And that's what we did.
SPEAKER_2: Thank you.
SPEAKER_2: All right, so where did the Yamanaka genes fit into this whole scenario?
SPEAKER_4: Oh, yeah, that's a good question.
SPEAKER_4: So Yamanaka 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.
SPEAKER_4: So he could now turn any cell into a stem cell.
SPEAKER_1: Which removed from the headlines all of the concern about embryotic stem cells.
SPEAKER_3: Right, because you didn't need to.
SPEAKER_1: It made it a non-story after that.
SPEAKER_3: Yeah, not to be confused with Yamanaka, who is a very funny black comedian.
SPEAKER_2: Thank you for explaining that, Chuck.
SPEAKER_3: No, I'm dead serious.
SPEAKER_3: Like I'm not even joking.
SPEAKER_4: And the reason that those genes are relevant is that those OS and K genes are a subset of the Yamanaka gene.
SPEAKER_4: So we don't use the full set because otherwise you'd go back to age zero and become a giant tumor.
SPEAKER_4: We use a subset of the Yamanaka genes, OS and K, and therefore it's very safe.
SPEAKER_4: You don't get to go back to zero.
SPEAKER_4: You just go back 75% of age and stop there.
SPEAKER_2: So, 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.
SPEAKER_2: Are there athletes out there at the moment experimenting with this sort of process to extend the bell curve of their careers?
SPEAKER_3: And do you want LeBron James' phone number?
SPEAKER_4: Well, some of my good friends are athletes.
SPEAKER_4: 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.
SPEAKER_4: And so it won't just be one day that we get to live longer, healthier, but we get to feel better, even midlife as well.
SPEAKER_3: So, Tom Brady played for a very long time and he had one of the most incredibly unappealing diets that anybody could have.
SPEAKER_3: And he attributes that to his longevity in the sport and his ability to not get injured and to recover.
SPEAKER_3: Is diet one of the most important things you can do to extend your life if you don't have this technology available?
SPEAKER_4: Right, yeah, Tom did all the right things.
SPEAKER_4: He didn't eat too much, he ate less often, he didn't eat three full meals a day, drank a lot of water, he gave a lot of massages to his muscles.
SPEAKER_4: All of these things trigger the body into survival mode, which is long-term very beneficial, slows down aging.
SPEAKER_4: And to me it was no surprise that he continued playing till he's late 40s.
SPEAKER_3: And survival mode is different than, you know, fight or flight mode, right?
SPEAKER_3: That's, you know, because a lot of people think survival, they automatically think fight or flight.
SPEAKER_3: So what would be the difference between survival mode and fight or flight?
SPEAKER_4: Yeah, well, fight or flight is more of a psychological stress.
SPEAKER_4: This is biological stress.
SPEAKER_4: The cells want to fight against adversity and try and survive.
SPEAKER_4: 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.
SPEAKER_4: And these genes that we discovered, the sirtuins, they get activated by fasting and by exercise and by certain molecules from plants like NAD, which you can take as a supplement.
SPEAKER_4: And so my father's been doing all those things.
SPEAKER_4: He's now 84 in literally perfect health, so he's a beacon of hope.
SPEAKER_4: He's not a clinical trial, but hopefully one day most people can live till their mid-80s and still be just as healthy as they were in their 40s.
SPEAKER_2: So we're talking about things that do us good.
SPEAKER_2: What's the criminal lineup for the worst foods we could put in our systems?
SPEAKER_3: Anything you find in America.
SPEAKER_4: Well, yeah, it's what you eat and when you eat.
SPEAKER_4: We overeat.
SPEAKER_4: We eat too often.
SPEAKER_4: And we also eat things that are just too many calories.
SPEAKER_4: So sugar is the biggest culprit.
SPEAKER_4: A lot of fat.
SPEAKER_4: I try to avoid meat.
SPEAKER_4: There are a lot of people who love meat.
SPEAKER_4: There's no evidence that a lot of meat extends your lifespan.
SPEAKER_4: In fact, a lot of the contrary.
SPEAKER_4: So yeah, those are the main things.
SPEAKER_4: And avoiding fresh foods is the problem in this country.
SPEAKER_4: We eat a lot of processed, highly processed foods, canned foods.
SPEAKER_4: These are not good because the wonderful molecules that slow aging have been destroyed when you cook them.
SPEAKER_3: So raw vegan.
SPEAKER_3: That's the life.
SPEAKER_1: There are some vitamins and nutrients that are in raw vegetables that you cannot digest through the fiber to get to them.
SPEAKER_1: So that there's an ideal cook time so that you can actually access the nutrients.
SPEAKER_4: That's true.
SPEAKER_1: It's like kale.
SPEAKER_3: They say you blanch it.
SPEAKER_1: Right.
SPEAKER_3: They say you blanch kale because otherwise you're just passing it through your system.
SPEAKER_3: It's not doing anything for you.
SPEAKER_4: Yeah.
SPEAKER_4: Well, 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.
SPEAKER_2: Chuck, they just stand there and shout at them.
SPEAKER_2: They're abusive.
SPEAKER_4: Exactly.
SPEAKER_3: Green tea matcha.
SPEAKER_4: Colorful vegetables.
SPEAKER_4: My partner Serena says eat the rainbow.
SPEAKER_4: That's a good start.
SPEAKER_2: Interesting.
SPEAKER_4: But not those candies that are rainbow, the plants that are colorful.
SPEAKER_3: That's giddles.
SPEAKER_2: You're taking away all the fun, David.
SPEAKER_2: We're heading towards medicine that is bespoke for the individual.
SPEAKER_2: Are we going to get to a point where gene therapy will not work for certain individuals or this is going to work for whoever?
SPEAKER_4: Well, given that it's working in dogs and in mice, it's probably going to work in people, I would imagine.
SPEAKER_4: It's working in monkeys as well.
SPEAKER_4: So I'm not so worried about that.
SPEAKER_4: I think this is a universal system.
SPEAKER_4: But we are entering a world where we can tailor the way we exercise what we eat individually.
SPEAKER_4: We all have different microbiomes.
SPEAKER_4: We have different gut lining.
SPEAKER_4: We have different genomes.
SPEAKER_4: And we can measure that now.
SPEAKER_4: 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, ten years later.
SPEAKER_4: And I think that cancer, heart disease and diabetes are largely preventable diseases right now with today's technology.
SPEAKER_1: Well, we look forward to this transforming the landscape.
SPEAKER_1: I can tell you that if we all live forever, we need another planet.
SPEAKER_4: That is very true.
SPEAKER_4: But I'll leave that one up to you and Elon to figure out.
SPEAKER_1: Yeah, we're coasting it to 10 billion people, and that's only if no one lives significantly longer than they currently do.
SPEAKER_1: We could probably sustain 10 billion, but not 50 billion or 100 billion.
SPEAKER_1: So keep it going.
SPEAKER_1: Delighted to get you for this session.
SPEAKER_1: And we'd like to check back in on you, maybe in a year or two.
SPEAKER_3: Or maybe 200 years.
SPEAKER_3: Who knows?
SPEAKER_1: You're going to show me that 10-year-old mouse.
SPEAKER_1: That's what you're going to show me.
SPEAKER_4: Yeah, or hopefully I can show you a person that's been cured of blindness.
SPEAKER_4: That would be great.
SPEAKER_2: Wouldn't that be great?
SPEAKER_1: Ooh, oh yeah.
SPEAKER_1: Okay, this has been another installment of StarTalk Special Edition.
SPEAKER_1: The epigenome and aging.
SPEAKER_1: Long overdue topic.
SPEAKER_1: Neil deGrasse Tyson here, your personal astrophysicist.
SPEAKER_1: As always, keep working up.