Longevity in the Lab

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BY KAREN HOPKIN
 

January 12, 2002 | AROUND THE WORLD, laboratories are teeming with creatures that have cheated death — or at least ducked it for a while. In Leonard Guarente's lab at MIT, yeast and worms with extra copies of the SIR2 gene live at least 50 percent longer than their wild-type counterparts. Worms in Cynthia Kenyon's lab at University of California at San Francisco remain spry two to four times longer than expected, thanks to mutations that disable a gene called DAF2. Meanwhile, in France, Inserm's Martin Holzenberger has found that mice missing one copy of the mammalian equivalent of DAF2 live, on average, 26 percent longer than normal lab mice.

The DAF2 gene and its rodent counterpart are part of a molecular pathway that controls how cells respond to a hormone called insulin-like growth factor (IGF-1). The pathway regulates resistance to various types of stress. The mutant worms and mice are better able to survive exposure to chemicals that generate reactive molecules that damage vital cellular components.

SIR2, it seems, feeds into the same pathway. It encodes a protein that regulates the expression of other genes — including those in the insulin-like signaling pathway. These discoveries, made over the past decade, did not only lead scientists closer to an understanding of the basic biology of aging. They've provided targets for pharmaceuticals that could be used to manipulate these pathways — and perhaps aging itself.


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