Fly Gene Stretches Life-Span

According to the Bible, Methuselah lived 969 years. Now, he has another claim on immortality: Geneticists have named a newly discovered fruit fly gene in his honor. The reason, reported in today's Science, is that fruit flies with a mutated methuselah gene live up to 35% longer than normal fruit flies.

This is not the first gene found to affect an organism's life-span. Researchers had previously identified a half-dozen in the worm Caenorhabditis elegans. But C. elegans can enter a dormant "dauer" stage, which enables the worm to survive long periods of adverse conditions, so some people had thought that genetic control of aging might only occur in worms. In most organisms, aging might be due to random mutations in individual cells.

To track down any aging-related genes in fruit flies, Yi-Jyun Lin of the California Institute of Technology in Pasadena and his colleagues generated scores of mutant strains. Then he tested how long the resulting mutant offspring lived and also how well they survived certain stressful conditions. One mutant yielded young that lived more than 100 days instead of the usual 60 to 80. The flies were also better able to resist stresses, such as hunger, heat, and paraquat--a herbicide that can damage cells by generating oxygen free radicals. That suggests, team member Seymour Benzer explains, that "if you can resist stresses or better repair damage, then you can increase life-span."

Still unclear is how the methuselah gene mutation makes flies more stress-resistant, but the amino acid sequence of the protein it makes may be part of a signaling pathway that controls how well cells resist or repair these stresses. If so, the function of the methuselah protein might resemble that of the protein produced by one of the worm's longevity genes, daf-2 (Science, 15 August 1997, pp. 897 and 942). The daf-2 gene is also part of a signaling pathway that influences how well cells age and cope with stress.

The finding means that "it's inescapable that aging is regulated deliberately by genes," says Cynthia Kenyon, a molecular geneticist at the University of California, San Francisco. And, she adds, because "it happens in both worms and fruit flies, you have to be crazy to think it won't happen in vertebrates."

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