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Science 290 (5499): 2137-2140

Copyright © 2000 by the American Association for the Advancement of Science

Extended Life-Span Conferred by Cotransporter Gene Mutations in Drosophila

Blanka Rogina, Robert A. Reenan, Steven P. Nilsen, Stephen L. Helfand*

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.

Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington CT 06030, USA.
*   To whom correspondence should be addressed. E-mail: shelfand{at}neuron.uchc.edu



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