Extended Life-Span Conferred by Cotransporter Gene Mutations in Drosophila

Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington CT 06030, USA.
Science (Impact Factor: 31.48). 01/2001; 290(5499):2137-40. DOI: 10.1126/science.290.5499.2137
Source: PubMed

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.

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