Authors: Rogina B; Reenan RA; Nilsen SP; Helfand SL
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.Keywords: Aging/*genetics; Amino Acid Sequence; Animals; Behavior, Animal; Biological Transport; Carrier Proteins/chemistry/*genetics/metabolism; Crosses, Genetic; DNA Transposable Elements; *Dicarboxylic Acid Transporters; Digestive System/metabolism; *Drosophila Proteins; Drosophila melanogaster/*genetics/metabolism/physiology; Energy Intake; Energy Metabolism; Fat Body/metabolism; Female; Fertility; Gene Expression; *Genes, Insect; Longevity/*genetics; Male; Membrane Proteins/chemistry/metabolism; Molecular Sequence Data; Mutagenesis, Insertional; Mutagenesis, Site-Directed; *Organic Anion Transporters, Sodium-Dependent; Sense Organs/cytology/metabolism; Sequence Homology, Amino Acid; *Symporters
Journal: Science (New York, N.Y.)
Date: Dec. 16, 2000
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Rogina B, Reenan RA, Nilsen SP, Helfand SL (2000) Extended life-span conferred by cotransporter gene mutations in Drosophila. Science (New York, N.Y.) 290: 2137-40.