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Extended Life-Span Conferred by Cotransporter Gene Mutations in Drosophila

Science  15 Dec 2000:
Vol. 290, Issue 5499, pp. 2137-2140
DOI: 10.1126/science.290.5499.2137

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Abstract

Aging is genetically determined and environmentally modulated. In a study of longevity in the adult fruit fly,Drosophila melanogaster, we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter—a membrane protein that transports Krebs cycle intermediates. Indy was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life-span. These mutations may create a metabolic state that mimics caloric restriction, which has been shown to extend life-span.

  • * To whom correspondence should be addressed. E-mail: shelfand{at}neuron.uchc.edu

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