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January 4, 2011

Genetic Timeclock

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Anti-Aging Gene (03.26.04) - Most of us think aging is inevitable, but one scientist has committed her career to proving us wrong.

Models of Health (2.04.03) - Geneticists are using new high-tech tools to study animals that live long lives, hoping to identify genes that may cause aging.


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Scientists are finding increasing evidence of a gene that plays a big role in how long you live. This ScienCentral News video has more.

Time Flies

"To lengthen thy life, lessen thy meals," Benjamin Franklin wrote in the June, 1733 Poor Richard's Almanack. It looks like he may have been onto something.

Scientists have known for years that cutting food intake, sometimes by as much as half, can lengthen life; this is known as caloric restriction, or CR, and it appears to be the only thing that slows the aging process in organisms from yeast to mammals. But little is understood about the cellular and molecular mechanisms behind how it works, and eating less can be a tough sell to people who love their food.

So Stephen Helfand, genetics researcher at the University of Connecticut Health Center, decided to study the phenomenon at the genetic level, wondering, "Can we find other ways of creating this same state as calorie restriction creates without having to calorie restrict?"

CR appears to trigger a gene called Sir (Silent Information Regulator) 2, which seems to be directly linked to prolonging lifespan in different organisms. What happens when researchers manipulate that gene? "What if we just altered the activity of Sir2?" asks Helfand. "Would altering the activity of Sir2 give us the same thing that calorie restriction might do?"

Other researchers have shown that activating the Sir2 gene in a single-cell organism, yeast, could lengthen life. They've also shown they could do it in a slightly more complex organism, a simple roundworm known as Caenorhabditis elegans. But would it work on more complex organisms?

fruit flies
The fruit fly Drosophila
To find out, Helfand studied the fruit fly Drosophila. He and his team created a mutant line of flies that over-expressed the Sir2 gene, and found that these flies lived up to 57 percent longer than flies in the control group. The team also disrupted the Sir2 gene in normal flies, put them on a calorie-restricted diet, and found no increase in lifespan.

"Our studies show that, in fact, when you increase Sir2, you live longer; when you block Sir2 from being able to be increased, you can block the calorie restriction response," explains Helfand, who reported his results in the journal Proceedings of the National Academy of Sciences. "When we increase the level of Sir2, either throughout the animal's lifespan as well as throughout all the cells, we get an extension of lifespan."

Other scientists studying the gene have found that Sir2 monitors the environment and sends signals to the body during lean periods. "Sir2 says, 'Let's just hunker down, let's slow down, let's not reproduce, let's slow down the aging process, and let's weather the storm, so let's survive longer," says Leonard Guarente, biology professor at the Massachusetts Institute of Technology who has been researching aging for over 12 years.

But merely surviving longer isn't the goal of this research—it's living healthier longer. "What we're trying to achieve is a longer lifespan while maintaining our healthy physiology longer," says Helfand.

Scientists who have studied the gene in yeast, worms, flies and mammals believe there's no reason to think the gene wouldn't function the same way in people. But more research needs to be done.

This research appeared in the November 9, 2004 issue of Proceedings of the National Academy of Sciences, and funded by the National Institutes of Health, the Ellison Medical Foundation, and the Donaghue Foundation.

       email to a friend by Karen Lurie

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