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Gene alteration points to longevity, thinness

Imagine that by altering the function of a single gene, you could live longer, be thinner and have lower cholesterol and fat levels in your blood.

Medical College of Georgia researchers are using a tiny worm called C. elegans to transform that vision into reality.

Researchers You-Jun Fei and Vadivel Ganapathy have found the Indy gene is critical in providing cells with energy, producing a transporter that helps deliver key ingredients of the fuel that drives cells. Indy delivers metabolic substrates such as citrate and succinate to cells where they enter the powerhouse called the mitochondria. Inside the powerhouse, oxygen also is critical to the biochemical reaction that occurs to produce ATP, the fuel for cells, says Dr. Fei, molecular biologist.

An unfortunate byproduct of this oxygen metabolism is reactive oxygen species, a sort of cellular trash that ages cells and may contribute to diseases from Parkinson's to Alzheimer's. "This is why people think we age; these byproducts of oxygen metabolism cause cells to degenerate," says Dr. Ganapathy, biochemist who becomes chair of the MCG Department of Biochemistry and Molecular Biology July 1.

That also is why decreased activity of the Indy transporter seems to make animal models at least live longer, healthier lives.

The MCG researchers have identified this longevity gene in humans, mice, rats and zebrafish as well as C. elegans.

Armed with a new $605,000, three-year grant from the National Institutes of Health's Institute on Aging, the researchers want to know the activity level that optimizes longevity and find compounds to control that level.

"The human lifespan is a phenotype determined by multiple genes," says Dr. Fei, principal investigator on the grant. "Our Indy gene is only one of the life-determinant genes. But I can say that when the function of this single gene is knocked down, the animal can extend its lifespan."

University of Connecticut r
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
30-Jun-2004


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