Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein.

Authors: Clancy DJ; Gems D; Harshman LG; Oldham S; Stocker H; Hafen E; Leevers SJ; Partridge L

Abstract: The Drosophila melanogaster gene chico encodes an insulin receptor substrate that functions in an insulin/insulin-like growth factor (IGF) signaling pathway. In the nematode Caenorhabditis elegans, insulin/IGF signaling regulates adult longevity. We found that mutation of chico extends fruit fly median life-span by up to 48% in homozygotes and 36% in heterozygotes. Extension of life-span was not a result of impaired oogenesis in chico females, nor was it consistently correlated with increased stress resistance. The dwarf phenotype of chico homozygotes was also unnecessary for extension of life-span. The role of insulin/IGF signaling in regulating animal aging is therefore evolutionarily conserved.

Keywords: Aging/*physiology; Alleles; Animals; Body Constitution; Carrier Proteins/genetics/metabolism; Crosses, Genetic; *Drosophila Proteins; Drosophila melanogaster/genetics/*physiology; Female; Fertility; Genes, Insect; Heterozygote; Hot Temperature; Insect Proteins/*genetics/*metabolism; Insulin/metabolism; *Intracellular Signaling Peptides and Proteins; Longevity/*physiology; Male; Mutation; Oxidative Stress; Protein-Tyrosine Kinases/genetics/metabolism; *Receptor Protein-Tyrosine Kinases; Receptor, Insulin/*metabolism; Reproduction; Signal Transduction; Somatomedins/metabolism; Starvation; Superoxide Dismutase
Journal: Science (New York, N.Y.)
Volume: 292
Issue: 5514
Pages: 104-6
Date: April 9, 2001
PMID: 11292874
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Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science (New York, N.Y.) 292: 104-6.

Study Lifespan Factors:
  • InR Insulin-like 1 receptor
  • Pi3K92E Phosphatidylinositol-3-kinase

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