Extended life-span conferred by cotransporter gene mutations in Drosophila

Science. 2000 Dec 15;290(5499):2137-40. doi: 10.1126/science.290.5499.2137.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / genetics*
  • Amino Acid Sequence
  • Animals
  • Behavior, Animal
  • Biological Transport
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Crosses, Genetic
  • DNA Transposable Elements
  • Dicarboxylic Acid Transporters*
  • Digestive System / metabolism
  • Drosophila Proteins*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / physiology
  • Energy Intake
  • Energy Metabolism
  • Fat Body / metabolism
  • Female
  • Fertility
  • Gene Expression
  • Genes, Insect*
  • Longevity / genetics*
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Mutagenesis, Site-Directed
  • Organic Anion Transporters, Sodium-Dependent*
  • Sense Organs / cytology
  • Sense Organs / metabolism
  • Sequence Homology, Amino Acid
  • Symporters*

Substances

  • Carrier Proteins
  • DNA Transposable Elements
  • Dicarboxylic Acid Transporters
  • Drosophila Proteins
  • Indy protein, Drosophila
  • Membrane Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • SLC13A2 protein, human
  • Symporters

Associated data

  • GENBANK/AE003519
  • GENBANK/AE003728