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Lifespan Gene (video)
June 07, 2002

Interviewee: Lenny Guarente, Massachusetts Institute of Technology.

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Produced by Sanjanthi Velu

Copyright © Center for Science and the Media, with footage from AARP, National Institute of Aging and Cynthia Kenyons (UCSF).

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Longer Life Mouse (video) - Some unusually long-living mice may reveal the secret to a long healthy life. (12/6/01)

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We all know that diet and exercise can help us live longer and healthier. For many of us that’s easier said than done.

Will there ever be a drug that can help us stay young longer?

This ScienCentral News video reports that there is hope, and some scientists say the key to a long life may be a single gene.

Staying Alive

Given the chance to live up to 150 years, most of us would readily grab it. Genetic research is beginning to indicate that some day it may cease to be chance and become more of a choice.

While there are many reasons we age, some scientists say that the mechanisms of one gene may hold the key to a long life. The gene in question is called SIR2, for Silent Information Regulator. SIR2 seems to be directly linked to prolonging the lifespan in different organisms, including man. Lenny Guarente, professor of biology at Massachusetts Institute of Technology, is studying how SIR2 is connected to calorie restriction, metabolism and aging in various organisms.

Calorie restriction and SIR2

Caloric restriction, a radical diet by which you cut a third of your caloric intake per day has long been known to increase lifespan in a variety of organisms.

Guarente says while calorie restriction is, thus far, the only proven way to increase lifespan, SIR2 plays an important role in this mediation. He’s shown that SIR2 monitors the environment and sends signals to the body during lean periods. "I think what SIR2 is doing is it’s telling the animalÖ if conditions are poor and for example nutrients are scarce, SIR2 says let’s hunker down, let’s slow down, let’s not reproduce, let’s slow down the aging process and let’s weather the storm," he says. "So let’s survive longer, so that when things get better weíre still standing and we can resume what we were doing."

The Youthful Worm

C. elegans or Caenorhabditis elegans, a small nematode, has been scientistsí best friend for quite some time. This 1 millimeter long roundworm has an average life span of just two or three weeks and hence is an ideal subject for scientists to study lifespan in a short span of time. This tiny organism also shares 74 percent of our genes.

Dr. Guarente and his collaborator Dr. Cynthia Kenyons at the Department of Biochemistry and Biophysics, University of California San Francisco, have been tinkering with the SIR2 gene in yeast cells (which we use to make bread and wine) and in the roundworm. It turned out that the manipulated SIR2 gene controls lifespan in both species.

"They could add one extra copy of the gene and the yeast cells lived longer and the most amazing thing was that exactly the same thing was true in roundworms," says Guarente "Its important to us because the evolutionary difference between yeast and roundworms is vast. So if this same gene is regulating the longevity in these two very different organisms, chances are that it is universal and its effects would include us."

The P53 gene

The scientists have also found "a relationship between the mouse SIR2 gene, that is most similar to the yeast SIR2 gene and another gene known as the P53 gene." P53 is a well-known cancer suppressor gene. When cells get damaged, rather than develop into mutations and become tumors, P53 simply calls these cells to commit suicide.

The problem, Guarente says, is that P53 activity remains turned on later in life and it is possible that unwanted cell death later in life causes the degeneration of organs. But if SIR2 modulates and fine-tunes that cell death as we age, " it’s possible that SIR2 will be able to ultra-regulate the survivability of organs and the whole animal," he says.

By manipulating SIR2 to modulate the activities of P53, could cancer cells end up living and mutating when they would normally die? Guarente says there need not be a trade-off. He is hopeful that they can develop a drug that can slow down aging and yet not promote cancer.

by Sanjanthi Velu

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