Biologist Cynthia Kenyon on Aging

The idea that aging is something that's not a given is a new paradigm

By David Ewing Duncan|Sunday, March 28, 2004

Cynthia Kenyon is a structural biologist who trained at MIT and at Cambridge University under the legendary Sydney Brenner, winner of the 2002 Nobel Prize in Medicine. In 1993 she stunned the world by announcing that her lab had suppressed a single gene in Caenorhabditis elegans worms—nematodes only a millimeter long favored by geneticists as model organisms—and doubled their normal life span. 

Recently, with a few more changes, she has extended their life span sixfold. Usually the worms live about 20 days. Her worms lived more than 125 days. More startling, the worms remained robust almost until they died. Kenyon is the Herbert Boyer Distinguished Professor of Biochemistry and Biophysics at the University of California at San Francisco. She is also the cofounder of Elixir Pharmaceuticals, a company that plans to apply her findings and those of other researchers to create a human antiaging pill.

I understand you wanted to be a writer when you entered the University of Georgia.

K: Yes, I was one of those kids who was always seeking the truth, and I first looked for truth by reading novels. It took quite a long time for me to realize there are better ways. My mother worked in the physics department as an admin, and one day she brought home a copy of James Watson’s Molecular Biology of the Gene. I looked at it, and I thought: This is really cool, you know, genes getting switched on and off. And I thought: I’ll study that. I loved the idea that biology was logical. A big tree seemed even more beautiful to me when I imagined thousands of tiny photosynthesis machines inside every leaf. So I went to MIT and worked on bacteria because that’s where people knew the most about these switches, how to control the genetics.

What you’re talking about is a whole new approach to disease, to health care.

CK: That’s exactly right. Age is the single largest risk factor for an enormous number of diseases. So if you can essentially postpone aging, then you can have beneficial effects on a whole wide range of disease. It’s radical. The whole idea that aging is plastic, and it’s something that’s not a given, it’s another variable, is a whole new paradigm.

But this seems too easy. Is there a catch?

CK: We’re so used to thinking that you can’t get something for nothing. But why would that be true? Humans live a lot longer than dogs, and we don’t suffer any penalty that I can see. We’re superior in almost every way—they can smell better. But really, they can’t drive cars, they can’t do half the things we can. I don’t understand why you can’t live longer and be really fit. Like our long-lived worms.

Can you make a worm immortal?

CK: I think that it might be possible. I’ll tell you why. You can think about the life span of a cell being the integral of two vectors in a sense: the force of destruction and the force of prevention, maintenance, and repair. In most animals the force of destruction has still got the edge. But why not bump up the genes just a little bit, the maintenance genes? All you have to do is set the maintenance level a little higher. It doesn’t have to be much higher. It just has to be a little higher, so that it counterbalances the force of destruction. And don’t forget, the germ lineage is immortal. So it’s possible at least in principle.

Is anyone trying to make an organism immortal, say, a short-lived organism such as a bacterium?

CK: One could try. I wouldn’t stake my life on it—though it is staked on it, in a way.

Many biologists don’t believe long life is possible in humans, much less immortality. Leonard Hayflick, the scientist who discovered that cells have a programmed moment of death, says that there is a natural age limit for organisms, that things wear out and die.

CK: When he heard about the worms, he apparently said that worms are just different, that it’s only true of worms but not mammals. But the fact is, it’s true of mammals now.

Would you want to live forever?

CK: Of course, if I’m young and healthy. Wouldn’t everyone? Here’s one answer to your question: How many high school kids really believe that they’re going to die? They think they’re immortal. They’re not disturbed that they think they’re immortal.

But that’s partly an evolutionary imperative. They need to go out and hunt, and be brave, and confront the world to provide food and a safe place to have children. If we were 80 but had the bodies of 20-year-olds, wouldn’t we be more cautious?

CK: I don’t know. You might be more cautious, or you might not be. I don’t know. That’s a really interesting question.

Wouldn’t you get tired of what you’re doing by the time you get to be 150?

CK: I might want to change jobs. In fact, wouldn’t that be fun? My hobby is finance, and I’d love to go into that world, or economics.

Is your company conducting mouse trials of an antiaging drug?

CK: We have animal data in the company, but it’s still in the early stages. We’re trying to make small molecules right now. We’re hopeful. We just got some preliminary information that looks great.

How would such a drug work in humans?

CK: Chances are, if it works, it works in incremental steps. At first, we are more interested in various diseases and making people feel better.

How would it be delivered?

CK: Our company right now is focused on a pill form. We’re working with compounds in mice, and they seem to have efficacy in mice, but we don’t know. It’s early. But it’s looking good.

At what age would one take this pill?

CK: We have studies in C. elegans showing that the daf-2 gene functions exclusively in the adult to control aging. So if you turn down this hormone system during development, and then you turn it back up in adulthood, there is no effect on aging. But at the beginning of adulthood, if you turn it down, you would live as long as you would if the gene were turned down your whole life. So it’s only the adult that matters, which is great. We don’t know yet whether you continue to get large effects if you turn down daf-2 late in adulthood.

So if you trick the body into thinking it’s young and it’s constantly replenishing everything, every cell. . . .

CK: It’s like building a ship where you could replace all the parts and keep it going forever. The catch, the big catch, is that there might be things you couldn’t do, you couldn’t replace. Who knows? 

There are people out there who object to the whole idea of extending life, such as Leon Kass, chairman of the President’s Council on Bioethics. He says we shouldn’t fool with these things.

CK: But we’re already fooling with it by treating disease. We’re extending life in many ways.

What about overpopulation?

CK: If everyone ages twice as slowly, you’ll still have the same percentage of old and young. So we’re not talking about filling the world up with elderly, infirm people. Overpopulation is a problem, but it’s already a problem. The best way to control population is to slow down the birthrate; in other words, to decrease the number of children and also raise the age at which parents have kids. My grandparents had many children when they were very young. If people have fewer children and they have them later, the birthrate will go down. This is already happening; it has to happen to sustain Earth. With a life-span-extending pill, the birthrate would have to come down just a little more.

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