A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function.

Authors: Tatar M; Kopelman A; Epstein D; Tu MP; Yin CM; Garofalo RS

Abstract: The Drosophila melanogaster gene insulin-like receptor (InR) is homologous to mammalian insulin receptors as well as to Caenorhabditis elegans daf-2, a signal transducer regulating worm dauer formation and adult longevity. We describe a heteroallelic, hypomorphic genotype of mutant InR, which yields dwarf females with up to an 85% extension of adult longevity and dwarf males with reduced late age-specific mortality. Treatment of the long-lived InR dwarfs with a juvenile hormone analog restores life expectancy toward that of wild-type controls. We conclude that juvenile hormone deficiency, which results from InR signal pathway mutation, is sufficient to extend life-span, and that in flies, insulin-like ligands nonautonomously mediate aging through retardation of growth or activation of specific endocrine tissue.

Keywords: Aging/*physiology; Alleles; Animals; Carrier Proteins/*genetics/*physiology; Corpora Allata/*metabolism; *Drosophila Proteins; Drosophila melanogaster/genetics/*physiology; Female; Fertility; Genes, Insect; Genotype; Insulin/pharmacology; Juvenile Hormones/metabolism; Longevity/*physiology; Male; Methoprene/pharmacology; Mutation; Protein-Tyrosine Kinases/*genetics/*physiology; *Receptor Protein-Tyrosine Kinases; Receptor, Insulin/genetics/physiology; Reproduction; Signal Transduction; Superoxide Dismutase/metabolism; Triglycerides/metabolism; Vitellogenesis/drug effects
Journal: Science (New York, N.Y.)
Volume: 292
Issue: 5514
Pages: 107-10
Date: April 9, 2001
PMID: 11292875
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Citation:

Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science (New York, N.Y.) 292: 107-10.


Study Lifespan Factors:
  • InR Insulin-like 1 receptor


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