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

  • Tatar M
  • Kopelman A
  • Epstein D
 et al. 
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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.

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Authors

  • M. Tatar

  • A. Kopelman

  • D. Epstein

  • M. P. Tu

  • C. M. Yin

  • R. S. Garofalo

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