Extended life-span conferred by cotransporter gene mutations in Drosophila.
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.
Rogina
B
B
Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington CT 06030, USA.
Reenan
R A
RA
Nilsen
S P
SP
Helfand
S L
SL
D000375:Aging / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003433:Crosses, Genetic; D004251:DNA Transposable Elements; D029382:Dicarboxylic Acid Transporters; D004064:Digestive System / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002149:Energy Intake; D004734:Energy Metabolism; D005216:Fat Body / Q000378:metabolism; D005260:Female; D005298:Fertility; D015870:Gene Expression; D017344:Genes, Insect; D008136:Longevity / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016297:Mutagenesis, Site-Directed; D029363:Organic Anion Transporters, Sodium-Dependent; D012679:Sense Organs / Q000166:cytology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D027981:Symporters
D002352:Carrier Proteins; D004251:DNA Transposable Elements; D029382:Dicarboxylic Acid Transporters; D029721:Drosophila Proteins; C417606:Indy protein, Drosophila; D008565:Membrane Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; C092524:SLC13A2 protein, human; D027981:Symporters