Extended Life-Span Conferred by Cotransporter Gene Mutations in Drosophila

• Published in: Science (American Association for the Advancement of Science) 2000-12, Vol.290 (5499), p.2137-2140
• Main Authors: Rogina, Blanka, Reenan, Robert A., Nilsen, Steven P., Helfand, Stephen L.
• Format: Article
• Language: English
• Subjects: Ageing, cell death; Aging; Aging - genetics; Amino Acid Sequence; Animals; Behavior, Animal; Biological and medical sciences; Biological Transport; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell physiology; Crosses, Genetic; Dicarboxylic Acid Transporters; Digestive System - metabolism; DNA Transposable Elements; Drosophila; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila melanogaster - physiology; Drosophila Proteins; Energy Intake; Energy Metabolism; Fat Body - metabolism; Female; Female animals; Females; Fertility; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene mutation; Gene mutations; Genes; Genes, Insect; Genetic engineering; Genetic mutation; Genetics; Heterozygotes; Indy gene; Insects; Laboratories; Life expectancy; Lipid metabolism; Longevity - genetics; Male; Male animals; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membranes; Metabolism; Molecular and cellular biology; Molecular Sequence Data; Mutagenesis; Mutagenesis, Insertional; Mutagenesis, Site-Directed; Mutation; oenocytes; Organic Anion Transporters, Sodium-Dependent; Protein metabolism; Proteins; Sense Organs - cytology; Sense Organs - metabolism; Sequence Homology, Amino Acid; sodium dicarboxylate cotransporter; Storage; Symporters; transposon P; Transposons
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.290.5499.2137

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.