Aubrey de Grey and Cynthia Kenyon on NPR
By Reason (re-posted from FightAging.org)
NPR recently ran a show interviewing a number of people who have given TED talks relating to aging, among them Aubrey de Grey, co-founder of the SENS Research Foundation and coordinator of rejuvenation research programs, and Cynthia Kenyon, whose work on single gene manipulations that extend nematode longevity back in the 1990s arguably kicked off the modern wave of interest in slowing aging. It makes for interesting listening; you should certainly take a little time and at least look at the transcripts.
In these short interviews you can see illustrated the most important division in the modern work aimed at intervention into the aging process: on the one hand the mainstream approach of altering the operation of metabolism so as to slow down aging, based on traditional drug discovery methodologies, and on the other hand the radical, disruptive approach of repairing the damage caused by the normal operation of metabolism, requiring the development of new biotechnologies. The strategy here is to avoid changing the operation of metabolism, because that is very hard and far too little is known of the important details, but rather periodically clean up the consequences of normal metabolic activity in order to prevent that damage from overwhelming and altering biological systems so as to cause degenerative aging.
As I'm sure all of you know by now, I'm greatly in favor of the latter approach because all the signs suggest it should be far more efficient and effective at extending healthy life spans, not to mention producing actual rejuvenation in the old. You can't greatly help the old by slowing down aging: better technologies are needed. Rejuvenation is needed. You can't bring aging under medical control by working on metabolic alteration to slow aging. Repair is needed, not merely dialing down the pace of new damage.How Do You Make An Elderly Worm Feel Young Again?
GUY RAZ, HOST:
So forget science-fiction, forget 20 years from now, Cynthia Kenyon is already there.
CYNTHIA KENYON: It was absolutely thrilling. I mean, unbelievable. I mean, it still makes my hair stand up just thinking about it.
RAZ: Cynthia's a molecular geneticist. She studies the biology of aging.
KENYON: It's something that you did not think would ever be possible. You would just get this feeling like you're looking into something that who knew was there? And I still feel that way. It's an amazing feeling.
RAZ: She's talking about a breakthrough in her lab, something she found in an unlikely specimen, a breakthrough that could change how long we humans live. Here's how Cynthia Kenyon explained it in her TED Talk.
(SOUNDBITE OF TED TALK)
KENYON: Have you ever wanted to stay young a little longer and put off aging? This is a dream of the ages, but scientists have for a long time thought this was just never going to be possible. They thought, you know, you just wear out - there's nothing you can do about it, kind of like an old shoe. But if you look at nature, you see that different kinds of animals can have really different life spans. Now, these animals are different from one another because they have different genes. So that suggests that somewhere in these genes, somewhere in the DNA, are genes for aging, genes that allow them to have different life spans. So if there are genes like that then you can imagine that if you could change one of the genes in an experiment, an aging gene, maybe you could slow down aging and extend life span. And if you could do that then you could find the genes for aging, and if they exist, and you can find them then maybe one could eventually do something about it.
RAZ: So Cynthia decided to try. And of all the species to answer these questions, she started with worms - a very strange sounding worm.
KENYON: Caenorhabditis elegans, or C. elegans. And they're beautiful, they're shaped like little horses' tails, but they're tiny. They're about the size of a comma.
RAZ: A comma.
KENYON: A comma, in a sentence, yeah. Very, very small. But they're really neat. They're cheap. You can grow lots of them. They have a very short life span. They only live a few weeks, but they get old, so that makes them very, very practical for scientific studies of aging.
RAZ: And what Cynthia and other researchers did with these worms is nothing short of amazing because by changing a single gene that's called the DAF-2, the C. elegans ended up living twice as long, and that was just the beginning.
KENYON: First, we doubled their life span. Then we extended it by six-fold, and then another lab was able to extend the life span for 10 times as long. The normal average life span of a worm is 18 days and these worms were 144 days old.
KENYON: OK so they were more - just almost 10 times as long as the average life span of a normal worm.
(SOUNDBITE OF TED TALK)
KENYON: In just two weeks, the normal worms are old. You can see the little head moving down at the bottom there. But everything else is just lying there. The animal's clearly in the nursing home. And if you look at the tissues of the animal, they're starting to deteriorate. You know, even if you've never see one of these little C. elegans - which, probably most of you haven't seen one - you can tell they're old. Isn't that interesting? So there's something about aging that's kind of universal. And now here is the DAF-2 mutants. One gene is changed out of 20,000. It's the same age, but it's not in the nursing home. It's going skiing.
KENYON: So it's aging, actually - this is what's really cool - it's aging more slowly. It takes this worm two days to age as much as the normal worm ages in one day. And when I tell people about this, they tend to think of maybe a 90 or 80 or 90-year-old person who looks really good for being 90 or 80, but it's really more like this - suppose you're - let's say you're a 30-year-old guy or 30 - in your 30s. And you're a bachelor and you're dating people, and you meet someone that you really like. You get to know her and you're in a restaurant and you say, well, how old are you? She says, I'm 60. That's what it's like. You would never know. You never know till she told you.
You would think to extend the life span of an animal for such a long time, you know, you'd have to kind of go around in a way and fix things or shore them up. You'd have to do something for the skin and something for the intestine, something for the nervous system. You'd have to - it would be really hard because old tissues all look old, but they all have their own separate problems. But what's the big surprise is that there are these systemic or system-wide control circuits that you can tap into. And what happens is that there are circulating factors, factors in the blood that can move through the animal and tell all the tissues to slow down their aging. Not to slow down their movement, but to slow down their aging. The great secret of all this is that, you know, all animals are much more similar to one another than they are different. Worms have muscles, they have nerve cells, they have serotonin, they have acetylcholine, they have all the neurotransmitters we have, the very same ones. So what that means is, you can easily interrogate the genome by making mutations to find genes that control things, things that you didn't even know were controlled, like aging. And there are actually hints that gene changes in humans that mimic the effects of these changes in animals may contribute to exceptional longevity to becoming a centenarian, in a human.
(SOUNDBITE OF TED TALK)
KENYON: So after we found - made our discoveries with little C. elegans, people who worked on other kinds of animals started asking, if we make the same DAF-2 mutation in other animals, will they live longer? And that is the case in flies. If you change those hormone pathway in flies, they live longer. And also in mice, and mice are mammals like us. So it's an ancient pathway because it must've arisen a long time ago in evolution so that it still works in all these animals and they also - the common precursor - also gave rise to people. So maybe it's working in people the same way. So for example, there is one study that was done in a population of Ashkenazi Jews in New York City. And just like any population, most of the people, you know, will live to about 70 or 80, but some live to be 90 or 100. And what they found was that there were - people who live to 90 or 100 were more likely to have DAF-2 mutations.
RAZ: It's so interesting because, you know, the whole idea of a fountain of youth is so steeped in human mythology, like, you know, these mythical fountains that people would go and drink from. But it actually seems like, I don't know, like, we might actually be getting closer to that.
KENYON: I think so, and I think to great benefit, I think so particularly because of this link between natural aging, which is a way bigger risk factor for, for example, cancer, than smoking is. I mean, it's huge. Aging is such a risk factor. If we could, you know, slow it down, then we should be able to counteract all these diseases. And those - I mean, those worms did have a terrifically wonderful health span, as well as life span. So we see it, so we know it can happen in these animals. Whether it can happen in people, we just don't know. But what I do think is that we can harness our bodies' own abilities that are kind of kept under wraps to allow the aging process to be slowed down. And that's the hope, is that we can do it in a way that counteracts lots of diseases and keeps us healthy right until the end.
RAZ: Cynthia Kenyon studies the biology of aging. You can see her entire talk at ted.npr.org
. In a moment - could we evolve into a disease-free species? I'm Guy Raz, and this is the TED Radio Hour from NPR.Can Aging Be Cured?
UY RAZ, HOST:
It's the TED Radio Hour from NPR. I'm Guy Raz. And on the show today, The Fountain Of Youth - the science and the ideas behind the quest to keep us living long and youthful lives. And we just heard from Dan Buettner. He's an explorer and a researcher who studies Blue Zones. These are the areas of the world where people live much longer than anywhere in the...
AUBREY DE GREY: Well, let me stop you right there. How much? How much? It's very important to look at the numbers here.
RAZ: Aubrey de Grey would argue the handful of extra years you can get from, say, a Blue-Zone lifestyle is really pretty minor.
DE GREY: People often laugh at the U.S.A. on this kind of thing because the U.S.A. spends far more money per capita on healthcare than any other country in the world.
DE GREY: And yet, if you look at the league table of life expectancy, it comes down in the 40s somewhere - like, 45 or whatever. But then if you look at the actual absolute numbers, the difference in lifespan between the U.S.A. and the number-one country, Japan, guess what it is? Just guess. Go on.
RAZ: I don't know - four years, five years.
DE GREY: Indeed, only four years. So you know - and these Blue Zones, you know, they might get another couple of years, but you know, the numbers are so small that we've got to do something that nobody has today.
RAZ: Aubrey is an Evangelist, probably one of the loudest voices for what might be described as the anti-aging movement. He's one of the leaders of a group called the SENS Foundation. It funds research into what he calls rejuvenation biotechnologies.
DE GREY: Which means new medicines that don't yet exist that will be able to repair the various types of molecular and cellular damage that the body does to itself throughout life and that eventually contribute to the ill health of old age.
RAZ: Aubrey basically looks at the human body in the same way he sees any other machine. You keep it oiled. You replace parts. You do preventative maintenance, and the machine can keep going a lot longer than it was ever meant to. So instead of just focusing on, say, a cure for cancer, he wants researchers to channel their energy into finding ways to prevent cancer and other diseases from ever developing in the human body in the first place. And he thinks if we could do that...
DE GREY: Basically, the types of things you could die of at the age of a hundred or 200 would be exactly the same as the types of things that you might die of at the age of 20 or 30.
RAZ: An accident, for example.
DE GREY: Exactly.
RAZ: Aubrey de Grey is a Cambridge-educated biologist. And we should just say at the outset that he does have a fair number of critics in the scientific community, many of whom say the science he's pushing is a little out there. But the idea behind that science is worth considering. It's the idea that we should see aging less as a fact of life and more like a chronic disease, one that we could do a lot more to manage.
DE GREY: I mean, I'm not saying that it's not good to live a good lifestyle and to maximize what we can do today. Of course it's good, but it's really only a tiny increase that one can get.
RAZ: Here's more from Aubrey de Grey speaking on the TED stage.
(SOUNDBITE OF TED TALK)
DE GREY: Please raise your hand if you want to get Alzheimer's disease. Please raise your hand if you think there is some age at which you will want to get Alzheimer's disease. Pretty much nobody wants to get sick, however long ago they happen to have been born. And therefore, it's really pretty bizarre that we don't put more effort into stopping people from getting sick, into trying to figure out how, medically, to alleviate the risk of getting sick as we get older.
But that's how things are. And yet, what we have here now is - since we've pretty much got rid of the infectious diseases as a cause of death in the industrialized world, about 90 percent of all medical care and all death is caused by the diseases of old age. These are universal, these diseases. Some people think, well, some people get Alzheimer's; some people get tuberculosis. It's all much the same thing. Nonsense - everybody gets Alzheimer's if they don't get anything else. It's not something that you can just avoid by being careful.
(SOUNDBITE OF MUSIC)
RAZ: Alzheimer's, dementia, cancer - these diseases occur because as you age, your body gets damaged. Molecules get damaged. Cells mutate. Junk accumulates in your body. All of this is natural. It happens to everyone. And Aubrey believes that that damage can be grouped into seven different categories, all of which could be prevented or at least slowed down.
DE GREY: So for illustration, let me just talk about one category.
DE GREY: Cell loss - what is cell loss? It's simply cells in a particular organ or tissue dying and not being automatically replaced by the division of other cells. Now, it turns out that that is actually an important contributor to certain aspects of aging - Parkinson's disease, for example.
Now, the thing is, we know what the fix for that one is. We know that the right way to repair that kind of damage is stem cell therapy. Now, progress in that area has been patchy over the past 20 years that people have been thinking about this. But now, it's going really well. There are a couple of clinical trials going on. And I'm really optimistic. I think most people are very optimistic. I would say that we've got a very good chance of actually totally curing Parkinson's disease with stem cells in the next 10 years, even.
DE GREY: That's one of the easier ones. A lot of the aspects of aging that we need to fix, however, are a lot harder. And I think, you know, we might be talking 20 or 25 years, and that's largely because they're less well-understood.
RAZ: I mean, you're saying that within 20 or 25 years, we can solve significant parts of the aging process. We can actually...
DE GREY: I would go a bit further than that. I would say that we can probably bring aging under comprehensive medical control within 20 or 25 years.
RAZ: I mean, if...
DE GREY: And of course, I do want to - I don't want to introduce - before you go on, I do want to make sure that I get my caveats in. First of all, I'm only saying probably. I'm saying we have at least a 50-50 chance of getting there in that time. I recognize that any prediction one makes about timeframes for anything that's more than even a couple of years away is extremely speculative. The other caveat that I definitely want to get in right now is, at the moment, we're probably going three times more slowly than what we could be going just because there's so little funding available for this critical work.
(SOUNDBITE OF TED TALK)
DE GREY: So I think it's all about this. I think it's that aging is so horrible, so scary that we have found it necessary to put it out of our minds and pretend that it's not horrible at all. And it doesn't matter how we do that so long as we can, so long as we succeed in tricking ourselves into the idea that aging is a good thing even though it doesn't look like a good thing. That made perfect sense. It was a rational thing to do until very recently because until very recently, nobody had any idea what to do about aging, but now we do. Now we are within a reasonable distance, within striking distance, of developing medicine that really brings aging under the same level of medical control that we have already today for most infectious diseases like, you know, tuberculosis or whatever.
It's like this. People will refuse to think about whether it's actually a good idea to defeat aging because they say, well, it doesn't really matter whether it's a good idea or not - does it? - because we're never going to do it. But the same people at the same time will also say - they will refuse to think about whether it's actually likely that we could do anything about aging anytime soon because who cares, because it's a bad idea, right? So the pessimism about the desirability and the pessimism about the feasibility join together to perpetuate each other.
(SOUNDBITE OF MUSIC)
RAZ: Aubrey's foundation, SENS, has a yearly budget of about $4 million, which is not a lot of money in the world of medical research, and it's why you can find so many talks and interviews with Aubrey online. He is nothing if not tenacious. But what's interesting is that for a 52-year-old guy who spends so much of his time talking about extending life, he says he really doesn't think about the end of his own.
DE GREY: I really don't. I'm too busy.
RAZ: This doesn't - it's not something that you're worried about.
DE GREY: I'm not a worrier.
DE GREY: I'm just not that kind of guy.
DE GREY: I'm a practical guy. I like to get things done. I like to make a difference.
RAZ: Do you think that, I mean, if in a world where people didn't die or didn't die as quickly that, you know, the sort of - the - I don't know - like...
DE GREY: That without, there'd be some kind of cultural ossification.
DE GREY: Well, I - well, I mean, it's a fair question. But honestly, it's not the kind of question that keeps me up at night.
DE GREY: 'Cause really, you know, first of all, even if we did have a problem right there, that's the kind of problem we'd like to have.
DE GREY: Can one really seriously say that it's as serious as this horrible curse that generally is preceded by this long period of decrepitude and disease and decline and dependence and general misery? You know, it's crazy to think that way. People have just got to get their heads together and have a sense of proportion.
RAZ: But you're arguing that the right investment in certain scientific research couldn't just get us to a hundred or 110, but it could get us to 110, playing tennis.
DE GREY: That's exactly right - in fact, keeping up with your granddaughter on the dance floor.
RAZ: Is that going to happen?
DE GREY: Well, I've just told you it would. You sound as though you don't quite believe me.
RAZ: I do, but you can understand why it still, today, in 2015, sounds like science fiction, right?
DE GREY: Things that are only - have only a 50 percent chance of happening in 20 years from now are supposed to sound like science fiction.
(SOUNDBITE OF MUSIC)
RAZ: Aubrey de Grey - you can learn more about his SENS Research Foundation or see several of his talks at ted.com