The Munk Debates Podcast - Be it resolved: Ageing is a reversible disease

Episode Date: October 6, 2022

Oxygen therapy to lengthen our telomeres and prolong the life of our chromosomes. Boosting the functioning of our mitochondria with NAD. Stem cell rejuvenation. These are just some of the exciting therapies that scientists are exploring in their quest to prevent the decline and suffering we experience as we age. But some scientists argue that these are just partial fixes and that the answer to the eternal quest for the fountain of youth lies in pinpointing the upstream driver of these hallmarks of ageing. They claim that thanks to breakthroughs in the science of genetics they have finally discovered the control system that generates the strength and health we associate with youth. It’s the “epigenome”, which is the packaging that coils around our DNA and switches on and off the genes that shape the identity of our cells. They say that as we age this packaging unravels, which deregulates the DNA and cell information they have been safeguarding. Fix the packaging and we can completely reset our DNA and cells and regenerate our bodies so they are once again like brand new. Skeptics say that we need to look no farther than evolution to recognize that while ageing can be slowed down it can’t be abolished. Despite the formidable powers of natural selection, a species that doesn’t age and die has not emerged. This is because ageing is marked not just by cells that are slowing down but also by cells that are rapidly multiplying and becoming cancerous. It is impossible to fix one without the other benefiting, a form of intercell competition where human beings and our hopes of eradicating old age are the losers. Arguing for the motion is David Sinclair, Professor of Genetics at Harvard Medical School and one of TIME Magazine’s “Top 50 people in health care”. He is the author of over 200 scientific papers as well as the New York Times bestseller Lifespan: Why We Age—and Why We Don’t Have To. Arguing against the motion is Joanna Masel, Professor of Ecology & Evolutionary Biology at the University of Arizona. She is a mathematical modeller who has published over 50 papers in a variety of scientific fields and is the author of Bypass Wall Street: A Biologist's Guide to the Rat Race. Sources: ZNews, Fox News, WKTV Newschannel2, Science Time The host of the Munk Debates is Rudyard Griffiths - @rudyardg.   Tweet your comments about this episode to @munkdebate or comment on our Facebook page https://www.facebook.com/munkdebates/ To sign up for a weekly email reminder for this podcast, send an email to [e-mail].   To support civil and substantive debate on the big questions of the day, consider becoming a Munk Member at https://munkdebates.com/membership Members receive access to our 10+ year library of great debates in HD video, a free Munk Debates book, newsletter and ticketing privileges at our live events. This podcast is a project of the Munk Debates, a Canadian charitable organization dedicated to fostering civil and substantive public dialogue - https://munkdebates.com/ The Munk Debates podcast is produced by Antica, Canada’s largest private audio production company - https://www.anticaproductions.com/   Executive Producer: Stuart Coxe, CEO Antica Productions Senior Producer: Christina Campbell Editor: Kieran Lynch Producer: Nicole Edwards Associate Producer: Abhi RahejaBecome a Munk Donor ($50 annually) to get 72-hour advanced access to the full length editions of Friday Focus and Munk Dialogues. Go to www.munkdebates.com to sign up. Hosted on Acast. See acast.com/privacy for more information.

There are options, and that's why we need to take this opportunity seriously. There's no way you can prevent global warming unless China is part of the solution. This is not normal male behavior. This is predatory behavior. We don't know how bad this bug is. We don't know what this bug does. All of that was thrown away in those eight minutes and 46 seconds, and that's the moment that I became an abolitionist. Extraordinary claims require extraordinary evidence. Welcome to the monk debates on every episode. We provide. you with a civil and substantive debate on a big issue of the day to provide each of our listeners

with enough information to make up their own mind. Today's debate, be it resolved. Aging is a reversible disease. The first time in history, scientists believe they've actually found a way to reverse aging, and the fountain of youth may come in the form of a hyperbaric oxygen chamber. Using a special previously overlooked protein found in our bodies known as FGF21 could have unleashed the disease fighting power of our youth. We gave these drugs and we delayed onset of age-related diseases as a group, not just one disease, but all of them. Hello, I'm your moderator, Rudyard-Griffis.

These are just some of the recent exciting advances scientists have made in the eternal human quest to escape the suffering and decline that accompanies old age. Some scientists say that we're on the verge of moving beyond partial fixes to the problem of aging to actually have the know-how to reverse the aging process itself. Thanks to recent breakthroughs in the science of genetics, these scientists say that we have pinpointed the control center behind aging, the so-called epigenome, which is the packaging that coils around our DNA and switches on and off genes that shape ourselves. As we age, this packaging unravels. Men the packaging, supposedly, and we,

we can reset ourselves so our body's biological age becomes younger, not older. Skeptics say that we need to look no further than evolution to recognize that while aging can be slowed down, it cannot be stopped, let alone reversed. Despite the formidable powers of natural selection, a species that doesn't age and die has not emerged. This is because aging is characterized not just by cells that are slowing down, but also by cells that are rapidly multiplying and becoming cancerous. It is impossible to fix one without benefiting the other, a form of cellular competition where human beings

and our hopes of eradicating old age are the ultimate losers. On this installment of the monk debates, we challenge the essence of these arguments by debating the motion, be it resolved, aging is a reversible disease. Arguing for the motion is David Sinclair, professor of genetics at Harvard Medical School and one of Time Magazine's top 50 people in health care. He's the author of over 200 scientific papers

as well as the New York Times bestseller lifespan, why we age and why we don't have to. Arguing against the motion is Joanna Maysell, professor of ecology and evolutionary biology at the University of Arizona. She's a mathematical modeler who has published over 50 papers in a variety of scientific fields and is the author of Bypass Wall Street,

a biologist guide to the rat race. David, Joanna, welcome to the Monk Debates. Thank you for having me. It's great to be here, thanks. This is going to be a fascinating debate. If there's one question that kind of grips all of us, it's the seeming inevitability of the aging of our bodies, our minds. Can anything be done about this?

I think the notion that there might be a way to, reverse the effects of aging, to extend our lives, to extend the quality of our lives, most importantly, as our society as a whole is getting older, is I just think one of these essential questions that deserves rigorous debate and analysis. So to have the two of you today with your considered opinions, your kind of deep knowledge and insights into this area is a real privilege for our monk debates community. So thank you so much for being part of the program. Very simple resolution today. Be it resolved.

Aging is a reversible disease. David, you're speaking in favor of the motion. Let's put two minutes on the clock and get your opening statement. We've got to define disease first up, I think. So a disease is a condition that results in disability, deterioration of function, loss of mobility over time. We think of aging as something separate, and that's historical, not scientific. historically we've put certain elements in certain buckets. We've been very good at defining different diseases that affect each of us while ignoring what causes 85% of diseases on the planet

and that's the process of getting older, which we call aging. Turns out the only difference between, if you look in a medical dictionary, what aging is versus disease is that a disease just happens to less than 50% of the population. And that's a totally arbitrary cutoff. What I'm proposing is that we should liberate us from that very narrow definition and start to think of aging as a common disorder, if not a disease. And the World Health Organization agrees with me having about a year ago declared that old age is a medical condition formally. What about the reversible part? Well, we've just published a paper in nature in December. It was on the cover, which we're extremely lucky and excited about, showing that at least in a mouse's

eye that you can reverse the age of the eyeball and make it function like it's young again, and not just make it seem young, literally the age of those cells at the back of the eye goes backwards. We can now measure age very accurately with a simple DNA test that's even being offered commercially for customers. Within 5%, it tells you how old cells are. So we flip those cells back to being young. We think not just temporarily, but permanently, they can now age out again. And those mice got their vision back after being old. And it worked for glaucoma, pressure in the eye, and it worked for damage to the optic nerve. So in terms of aging, just because it's common, we shouldn't declare it as being separate from disease. And it's definitely reversible. And there

are hundreds of lives around the world that are working to find other ways to reverse aging in the bodies of mice and in dogs and humans as well. Thank you, David. Fascinating. I'm really looking forward to this debate unfolding. And the next step in our conversation today is Joanna's opening statement. So, Joanna, a couple minutes on the clock. Set out your argument for why you think aging is not a reversible disease.

So I agree with what David said about what a disease is. But I want to clarify what we mean by aging. Even if we got rid of aging, we still wouldn't be immortal. or we'd all die of something eventually. But what ageing really means is that usually it's defined in terms of dying, that every year your chance of dying goes up. Things in your body don't work as well. And as that happens, it becomes more and more likely that you will stop working altogether.

And I'm happy to sort of maybe treat that as a disease, but at least to recognize it as two broad classes of disease, both of which lead to deterioration and increasing death rates. Now, I'll call them senescence and cancer. So senescence means that stuff stops working. And I think this eyeball example is probably a great one and it can totally be reversed. I don't disagree with David on that. The issue is cancer.

Cancer means your cells are actually working just fine. In fact, they might be working more vigorously than before, but they're working for themselves. They're not working for you. They're putting their interests above yours. And it's possible to fight individual cancers, but a huge part of the aging process is the tendencies for new cancers to appear more often as you get older. And what I'd say is that tendency is not a reversible disease, unlike making individual cells younger. So what we found in our mathematical work was a sort of an insolvable double bind between these two types of diseases. So option A is

you just let the cell senesce and then of course you're going to age. Option B is you get rid of the bad cells. You replace them, you reprogram them. But one way or another, you now have some level of competition among cells of the type you want and cells the type you don't want. And as soon as you have any process in which cells compete, then some cells are going to be very good at competition, which means they're going to cause cancer. And you're going to age from cancer or at least sort of pre-cancerous clonal expansions they're called, which are also cheetah cells, even if we don't not quite call them cancer. Essentially, there's no option C. Cells either compete or they don't compete. If they don't compete, you age of senescence. And if they do compete, then you age of

cancer accumulation. So either way, you age. There is no third option. Fascinating stuff, Joanna. Thank you. Both of you explaining things in terms that even I can understand. So I appreciate that as a non-scientist. David, back to you, your chance for rebuttal, another two minutes on the clock you to react to what you've just heard from Joanna? It seems like we agree about senescence. And one way to think of senescence broadly is that our cells, we believe, lose their identity and their function over time. They essentially lose their ability to read the right genes at the right time.

The same way an old pianist cannot play a beautiful concerto anymore, having lost their eyesight. This is very similar. And so we agree on that. And what happens at the very end of that life cycle of those cells is that they senes. and they become zombie-like in the body, and they accumulate. And there's a lot of evidence that this accumulation of these zombie cells is a problem. They wreak havoc on the immune system. They cause inflammation.

And they promote cancer, which brings me to the next point, which is, I think that cancer is a really, really interesting point to bring up. In fact, it really does come up in debates that I've been in. So let's drill down on that. There are things that aging is going to cause that kill us. I don't believe in immortality, by the way. I just want to address that. I believe that we are capable of having much greater and effective medicines

by tackling the root causes of aging rather than tackling diseases once they've already occurred, such as cancer. And so I would first of all say that don't be discouraged by what you're hearing from Joanna that cancer is inevitable and we're in trouble. Aging research can definitely prevent cancer. if you calorie restrict or intermittent fast, a mouse or a rat or even a dog, you'd greatly reduce the chance of getting cancer. So you can delay it.

What about reverse it? Well, I agree it's very hard to say right now that you can make a cancer cell behave itself. You can kill it off. We're getting very good at that, especially with the immune system. But is it possible to take a tumor and make it essentially go away by making it younger again? We don't know the answer to that. And in fact, we're researching that right now. What happens if you take a cancer cell and make it young?

Does it die because it cannot handle being young? Or does it even get more aggressive? We don't know that yet. So that's a scientific question. But in terms of this debate, I would say that just because we don't have the technology or the knowledge about how to address cancer that particular way, and if we just have to kill them off, so be it, I don't think that that refutes the argument that aging is a reversible disease.

It says one component of the outcome of aging is problematic and we just need to work harder to find solutions. Thank you. David, now we're going to go to you, Joanna, for your rebuttal. You can react to either David's opening statement or what you've just heard now. So it sounds like we agree about a lot of stuff. Really, what's at the heart of it is the nature of cancer as a disease of aging. I agree that sometimes we can reduce cancer through things like calorie restriction and obviously not smoking and so on. But that doesn't mean that we reverse the underlying disease of aging that cancer is one component of. So essentially, one force you can't fight in biology is evolution.

You know, there is competition. there is selection of the fittest, and that applies to cells too. So we start out with ourselves all merrily cooperating with each other because they've been programmed to do that. And then we apply selection to them, where we give them every opportunity to cheat, and we put in lots of mechanisms to try and stop them cheating, and then we supplement them with drugs and so on

to try and kill the cheaters and so on and so forth. But the fact is behind that, there's an evolutionary process. And we have set it up to fail if you give natural selection time to solve a problem, like how do I break free of this tiresome organism I'm in and start working for myself instead of for it? That's going to happen. So we do have the knowledge that evolution does find a way. We do have the knowledge from deduction, from reasoning, that if cells compete, then they will evolve to become very good at competing, and they will do so

at the cost of the organism. And the point of this is it is a time-dependent process. Aging means getting worse with time. So you can slow that process. And I'm actually very optimistic as well, that there are all sorts of things we can do to have longer lifespans and longer health spans. But that's very different from claiming that you can reverse the process, that there's a lot of there isn't an inevitable ratchet at which evolution comes up with innovations of the cells to thwart the interests of the whole organism. Thank you, Joanna. Now I get to jump in and try to kind of channel some of the thinking of our listeners here

reflecting on this debate so far, which has been excellent. And David, maybe just have you react to Joanna's point right now. And in effect, an argument that life surpasses the concepts that we impose upon it, that this contention that you're arguing for, that aging is reversible, that's the sticky part of this resolution, the word reversible. Why are you optimistic that we can impose on nature

behavior that is contrary to biology? Well, because we're humans. We do what we want with our technology. Ever since we picked up a rock six million years ago, we've been innovating to make our lives better. there's nothing about our current situation. Everyone should look around the room. What is natural about our existence?

There's nothing. I mean, an air-conditioned room talking to you through electrons. Same is true for healthcare. We've fought against diseases over the last few hundred years. In fact, you could argue thousands of years. This is what we do. And so to say, well, let's just accept evolution the way it is, I think is not a tenable argument.

There are technologies that do definitely allow us to reverse. aging. This is not even up for a debate. It's in the scientific literature. I've given an example of what my lab has recently published. But there are examples even in humans of being able to turn back the clock at least a couple of years with a few months of treatment. The experiment included nine healthy participants who were given a mixture of drugs for one whole year. The drugs essentially included one growth hormone to check whether or not the growth hormone can be securely implement. in humans to revive the lost tissues in the thymus gland. The study primarily concluded the fat accumulated in the glands after puberty

was replaced by reformed thymus tissues, therefore showing positive signs of age reversal. The participants shared around two and a half years of their biological age. This is Stephen Horvath and Greg Faye's workout on the west coast of the US. And so while we're very good at getting better at slowing, down aging. In the past four or five years, there have been real breakthroughs in discovering that from mice to humans, you can reverse not just some aspects of aging, not just I'll make you feel better, but actually turning back what is recognized in science as the biological clock, which we can now measure pretty easily even with just a blood test or a mouth swab. You can actually reverse the

metabolic age of a cancer cell. This is an example of age reversal. There's what I'm sure Joanna is aware of, a effect called the Warburg effect, where cancer cells become addicted to sugar, and this is part of the aging process we've published. It's called the Gorongogenesis hypothesis that as we get older, our bodies become more cancer-like, and this is conducive to cancer cells running away in our body. And there are drugs that work by correcting that metabolic change that occurs during aging in our bodies and specifically, hopefully in the cancer cells, which actually causes the cells to die because they get addicted to sugar and they don't like being switched back to being younger again. So that is, I think, a very good example that we are getting better

at being able to reverse the age of cancer cells and it can be effective to even treat that disease. Good, Joanna. So follow up on that. In a sense, David's making an argument here that we're not contingent on our biology. In fact, what we're contingent on is our technology. and our ability through technological innovation, through techniques that are ongoing and accelerating at labs around the world like yours and David's, are positioning us right now, not in some hypothetical Steven Spielberg future, to tackle the big problems of cancer, which you've outlined and in a sense dominate biology. Why do you believe that that's less likely as opposed to more?

So I'll tell a roundabout story since David and I are obviously from our accents, both Australian. And so for that reason, I'm going to quote the former Australian Prime Minister, Malcolm Turnbull. And in 2017, in a completely different context, it was the context that he didn't really like how cryptography worked. He said, the laws of mathematics are very commendable, but the only law that applies in Australia is the law of Australia. And it's just not true. Just like the laws of mathematics did not let Malcolm Turnbull read encrypted messages, the laws of mathematics apply to evolution by natural selection as well. Mathematically, cells compete or they don't compete.

Like there isn't a middle ground. There's nothing in between those two things. I don't dispute that the sorts of aging that, come from cells not competing can be reversed. And I don't dispute that individual cancers can be reversed, most simply by cutting them out, for example. But the tendency for the cooperative organism to break down when subject to competition follows from logical mathematical principles. And so David has argued here from this very human exceptionalism where gods, we can do anything. And no, we can only do what the laws of mathematics allow us to do, whether it pertains to cryptography or to evolution.

Well, David, I want to hear you come back on that. I think that's an interesting point. Joina is saying there's limits here, just like there's limits with physics, there's limits with biology. And regardless of what technology we have, we're not living in a Star Trek future yet. Is that fair? We're definitely living in a Star Trek future. I'm talking to you through a communications device right now. But in terms of biology, you were a little bit behind engineering because molecules in biology are a lot more complicated. But we're getting there. Joanna's undoubtedly a better mathematician than I am, but I'm happy to jump in.

I believe and have evidence that aging is, if you boil it down, a loss of information. And there's a lot of excellent mathematics behind the information theory of communication, in particular the reason we can talk to each other and send photos of the internet was solved way back in the 1940s by Claude Shannon at MIT. And if you boil down, if I distill aging, you come down to that equation, which is basically the laws of information preservation and entropy. And without getting into the math of that, which would bore everybody, what I can say is that if you regard aging as a loss of information, then a lot of it makes sense. We can see in cells that the information is encoded in two different forms.

There's the digital code, which is the DNA with four letters, ACTG rather than zeros and ones. And then there's the control systems that are three-dimensional and biological called the epigenome, and that's there to control the reading of the information in the same way a laser beam is reading the code on a compact disc or DVD. And that's how cells work. And aging, I've proposed, is primarily the loss of the ability

to read that digital information. But here's the important point. What we showed in our paper in nature is that there's a backup copy of the information. The same way when you send an email, it's kept as a backup copy until you receive it up in the ether in TCPIP protocols. That in itself I regard as extremely good evidence, I would never say the word proof as a scientist, biologist at least, that the evidence that there is information encoded in ourselves that is able to go back to an early state and read the genetic information the way we did when we were young. And the fact that we can do that in the eyeball doesn't rule out the possibility of doing it in other tissues and cells,

perhaps even to help with cancer cells. But that's really the essence here is that if we'd had this debate two years ago, I couldn't have been as definitive that aging is reversible. Fascinating, David. So, Joanna, what's your reflections on that? I mean, David is using in a sense, an analogy here to computers, the computers we're using to speak with each other, that our body is capable of storing a kind of an original code that we can bring out to debug ourselves, to kind of defrag our hard drives when we all hit 65.

Are you equally enthusiastic about that? So as a useful for slowing aging, for, you know, helping individuals, sure, as a contradiction of the mathematical, you know, proof that aging is irreversible, whatever, its speed, no. So David has essentially evoked the second law of thermodynamics. Hi, Monk listeners. If you're like me, you probably need a little reminder of what exactly the second law of thermodynamics is. No worries. If you skip that grade 11 physics class, we've got an explanation for you right now. The law of thermodynamics, the second.

Second law states that entropy, otherwise known as disorder in the universe, always increases over time. In other words, systems will always progressively deteriorate. And that's Joanna's point. It's that the law of thermodynamics, the second law, also applies to the human body. Now back to our program. All I'll say is it applies to the backup copy too. You know, the original copy degrades fast. The backup copy degrades slowly. Everything degrades. David's done a lot of great work on epigenetic marks, but there are also mutations that occur. And then there's also stuff that goes wrong at the protein level and the accumulation of misfolded proteins and all kinds of changes that happen during aging. To completely reverse it, you have to find all of them. You have to make sure that

you not just use the backup to fix the original, but you also need to fix the mistakes that happen in the backup, not just fix the DNA and the epigenome, but also fix the protein junk, that absolutely all of it needs to be fixed. And an organism ultimately is as strong as its weakest link, and you will miss something. You are not going to get everything right for every cell, every molecule, every epigenetic mark, everything. And the stuff you miss, that variation will be subject to natural selection or will degrade in some critical component and whatever the weakest link is, that will get you. And those weakest links are declining over time in a process that's a one-way process,

just like the Second Law of Thermodynamics specifies a one-way process. So, David, I mean, there are 15 trillion cells in the human body. That just seems like an incredible challenge to go through those using this. I guess primary code, this original source data to clean it all up. In practicality, how is this going to happen? Right. I think I count 26 trillion. But there's a lot of cells.

Okay. But yeah, there's no question. I'm not going to try and refute the second law of thermodynamics. That would be a pretty hard argument to make. And I'm not making that point. But what I am saying is that you can reverse. the outcome of aging. I mean, we've proven it.

You can bring back eyesight to a mouse. And for that to happen, we have shown, and we must be recovering a lot of that information. It's similar to a scratch DVD being polished. You can now play the music. No one has said that all the scratches have gone perfectly. You can never restore it to an original state, but it functions just as well as it was new.

And that's what we've shown with this paper, with the mice. So I think where it's coming down to in this debate, and I appreciate Joanna's comments, where we're coming down to is, I'm saying aging is a reversible disease, and Joina is saying aging isn't a completely reversible disease. We're very close on that,

and I'm not here to say that we're going to live forever, or we could always maintain the information that we received from our parents, both genetic and epigenetic. But I do think that aging is far more reversible than we ever thought just a couple of years ago. And David, to what extent are you optimistic? And maybe could you give us a sense of the time frame that you can go beyond simply,

you know, a mouse's eyes. I mean, that is in itself a remarkable accomplishment, but into, you know, more complicated systems like the human brain, like cancer in large body organs. I mean, is this something that you think is imminent or is this something that's decades away? Well, it's always dangerous to predict the future, of course, especially in biotech. But what I can say is that other researchers, besides myself in Spain, in Salk Institute, they have already shown it as possible to reverse the age of muscle and the brain in rodents.

You might say, well, okay, well, that's just a rodent, but a rodent brain is pretty complicated, too. It's not that too far away from us. But it's always the devil's in the details. Having to show safety is a major issue, a challenge, etc. Where we're at, you know, I'm an innovator. I've started over 15 companies, not because I'm chasing some monetary thing. It's more that I want to see these technologies help people before I fade away. And to that end, this discovery a couple of years ago was spun out into a company that is called Life Biosciences.

and they're at the point of doing the safety studies to at least see and convince the regulatory authorities in the US to do a human study to reverse blindness in humans, which would probably be about realistically a couple of years away before we know if it works in humans. But for other tissues, yeah, I mean, we'll tick them off, we'll see. The good news is that there are dozens and soon to be hundreds of labs working in this area. So it's going to take off really quickly similar to the way CRISPR gene editing

took off about 10 years ago. So Joanna, to come back to you on a similar question, you're clearly saying in this debate that aging isn't reversible. You agree that it can be slowed. How optimistic are you about when these technologies will become widely available? And more importantly, when they'll move beyond testing simply on animals to actual therapies that could work on human beings? There are already things you can do to slow down aging,

quitting smoking definitely comes very high on the list, not, you know, getting sunburned and spending too much time, you know, in difficult extremes of environment. There are things, you know, not eating too much. I mean, we already have fairly straightforward things to slow aging down, staying in good physical shape without straining the body and so on. There will be high-tech things we can do too, and those are fantastic. and I am fairly optimistic that some of them will become available. But I really want to be cautious about some of them. Part of our finding of a double bind means that there's a close link

between senescence and cancer. So every time we have a promising new treatment, maybe it works in animals, maybe it works in the lab, maybe it even does well for very specific groups in a clinical trial. But if it is a treatment for a kind of senescence, there is a huge danger of a flip side that it will cause cancer. And sometimes that trade-off will be worth it and that individual will benefit from it. And other times it will be not that the costs in terms of cancer are worse than the

benefits in terms of reversing senescence. And I think it's always important to recognize that there will be trade-offs whichever away they go and those trade-offs might be different for different people. Fascinating. David, do you believe in that trade-off theory also or do you see that there could be some unamiliorated good here that could be realized through these technologies where you wouldn't be, let's say, sacrificing increased eyesight and renewal of your eyesight, but also possibly an increase of cancer of the optic nerve? I think it's okay to rely on mathematical models, but if they are refuted by the data then we have to revisit those ideas and those models.

And that's really what I like to do in my lab is to not have too many assumptions and let the organism or the cells tell me what's going on. And I used to have an assumption, for example, that when we extended the lifespan of whether it be a yeast cell or a worm, a fly or a mouse, that there would be a trade-off. And we used to think that fecundity, fertility would be a of or cancer. And that made a lot of sense. It was comforting, you know, that the world is in balance. But what we've seen, and by we, I mean, but dozens of labs around the world, not just my lab, is that in every one of these species that I've mentioned, it is possible and actually more typical when you extend the lifespan and slow down aging in one of those organisms that you have

accordingly increases, not decreases in fertility, and also a decrease in the amount of tumors in organisms that get tumors. And the way to think of this is that what often we don't realize is that our bodies have inbuilt survival mechanisms that are in part controlled by how much we eat, when we eat, how much we exercise. And our current lifestyle in the modern world basically tells them, don't worry, everything's good, we're not going to starve tomorrow, there's no saber-tooth cat chasing us, so shut down your survival and health providing longevity genes. And that actually means that if we can turn them on through changes in lifestyle or by medicines that I and others are working on, we can have our cake and eat it too. We can have the

body survive for longer. In the same way a turtle can go for two, three hundred years without getting cancer or a whale if you want a closer relative. And you get those health benefits, but that also includes extended fertility and the decreased amount of cancer. It's extremely difficult to cause cancer in an elephant, even though they have many, probably 50 times more cells than we do. And it's not a law of biology. It's just that they have more copies of P53, which is a tumor suppressor. And these very small tweaks, if we gave ourselves five copies of P53 instead of one, we might be able to go for 200 years without getting a tumor. I'm more of an empiricist than a modeler, as you can tell. Thank you, David. Before we go to closing statements,

I always liken these debates to just spend our last moment together to ask you each, which of your opponent's arguments would you give the greatest credence to? I think it's always fascinating to hear versatile thinkers like both of you kind of put yourself in the other person's shoes. So having Joanna, a listen to, to David in this debate, which of his kind of contentions, key points here, do you think is the most credible in making his case, as he has throughout this debate, that aging is indeed reversible? Which of his arguments should we pay the most attention to? I don't believe in arguments against mathematical laws giving credence. I can say which of his arguments

put the most credence that aging could look radically different for humans in the future. rather than the strong statement of being reversible. And I think the prevalence of what David called backup copies is some of the most striking evidence that aging could look radically different and significantly slower in the future. Well, thank you, Joanna, for playing along with me on that. So David, similar question to you,

which of Joanna's arguments, you know, that she's marshaled against our resolution, be it resolved, aging as reversible? Which one of those worries you the most? Which one of those kind of creates that possibly niggling seed of doubt? Well, I haven't argued against any mathematical laws. I said models, which I are always revisable. But Joanna makes a really good point bringing up cancer. That is the major issue with what we're working on, which is we may be able to keep the body young and even reverse its age, but once a tumor gets hold or takes hold and spreads, then it's not clear yet and may actually, it might not be possible to use these same technologies to address that particular disease of aging. And so that's a valid point. And we're

one that actually hasn't been raised in any debates I've been in, and it's going to, I think, require some extra thought about how to put that into the overall theme of reversibility of aging. But I will just make the final point that that's one disease out of dozens that we have to contend with. And if cancer is the only thing that we're left with, then I'll be a happy researcher. Sure. Thank you, David. Likewise, for playing along with me there. And thank you both for what's been a really terrific debate. I feel like despite my lack of any deep knowledge of this subject matter, you've kind of brought me along on a really fascinating kind of scientific journey here. So let's go to closing statements and wrap this debate up. Joanna, you're going to go first, two minutes on the clock for you to make your final points opposing our resolution, be it resolved, aging is a reversible disease. So just to repeat that I think there are these two fundamentally different kinds of diseases and this nescent style of disease which is reversible and the cancer style of disease which while individuals cancers are reversible the general tendency for cooperation to break down

is not reversible. Immortality is actually possible in biology but it requires natural selection And natural selection requires failures. Something has to fail to live or fail to reproduce. If all you're looking for is well-functioning cells, then it's enough for cells to fail or be destroyed by drugs or reprogrammed back to their backup copy or whatever. But to get well-functioning whole organisms, it needs to be whole organisms that are subject to natural selection,

whole organisms that either succeed or fail. So the way to be immortal is to have children and grandchildren. Obviously, ourselves are capable of immortality. Our germ cells give rise to those children and grandchildren. But the process that keeps them immortal, as opposed to them getting more and more mutations until eventually they're overloaded with them, is that not all of our children and grandchildren make it.

And that is part of what really is a mathematical law, which is you input, it's a deductive statement for evolution. It's variation plus selection plus inheritance gives you evolution. And while there are assumptions in this kind of deductive statement, those assumptions are so well accepted empirically that they're really not open to dispute. And the same is true for the double bind. It has assumptions like humans have a division between German somers cells. and generally speaking, mutations make things worse

and other assumptions like that that are definitely model assumptions, but they're not ones that are particularly open to dispute. So, souls compete or they don't compete, there's no middle ground, there's no way of squaring that circle, and given those trade-offs between cancer and senescence, I welcome medical advances,

but I think we have to be extremely careful that we're not accidentally doing more harm via cancer than good. Thank you, Joanna. Well, David, we're going to give you the last word in our debate today, be it resolved, aging is a reversible disease. Let's have your closing words. There are two main arguments that I've made. One is that based on evidence from experiments in biology

that it is possible to reverse aging in complex tissues, such as the eye and as my microcontracts, colleagues have shown in the brain and in the muscle, and we'll keep ticking off the tissues where it's possible. So that part, I don't think is debatable. On this, the second point about evolution where Joanna and I haven't really engaged directly. So evolution can also tell us why we age. The reason we age is that there's no adaptive benefit to a species sticking around for longer than it needs to to ensure the replacement of its gametes, its DNA. And so humans, over the last few million years,

haven't needed to live beyond about 50 years of age because they're going to die from war and famine, etc. Young men used to die at war pretty commonly. So there's no advantage to having a human that lived 200 years if it was never going to make it that far. But we live in a world where humans can live 200, 300, 300 years, but we cannot wait for evolution to catch up. So that's why we need to turn to species

that have been at the top of their game, at the top of the food chain for many millions of years, such as whales and elephants and tortoises and trees. And what they've shown is that there's no law of biology that says we cannot slow down aging, that we cannot live for hundreds of years. And as we're learning by deciphering the genomes and the epigenomes of those species, we can apply those advances to our own medicines and perhaps to our own bodies one day to give us the resistance to cancer and the other diseases that we currently, and typically, unfortunately, regard as simply just being part of life's natural process.

Thank you, David. And thank you, Joanna. This has been, again, a terrific debate, mind expanding. We've touched on, I think, all the key points that I wanted us to reflect on for the benefit of our audience. So on behalf of the Monk Debates community, thank you both for coming on the program today. Thanks for having us. Thanks for having me. Well, that wraps up today's debate.

I want to thank our participants, Joanna and David, for a terrific conversation. Giving me so much to think about. This is clearly a vital subject matter for all of us to dig in more. Go to our website to check out Joanna and David's bio. Look for their books. Lifespan by David, why we age and why we don't have to. And Joanna's bypass Wall Street, a biologist guide to the rat race. You can reach us at Podcast at Monk Debate.

com. While the monk debates is that special place for civil and substantive debate on the big issues of the day, thank you for lending your voice to helping us bring back the art of public debate one conversation at a time. I'm your host and moderator, Rudyard Griffith. The monk debates are produced by Antica Productions and supported by the Monk Foundation. Rudyard Griffith, Christina Campbell, and Nicole Edwards are the producers. Api Rahaja is the associate producer. The Monk Debate podcast is mixed by Kieran Lynch. The president of Antica Productions is Stuart Cox. Be sure to download and subscribe wherever you get your podcasts.

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