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Science 292 (5514): 107-110

Copyright © 2001 by the American Association for the Advancement of Science

A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function

M. Tatar,1* A. Kopelman,1 D. Epstein,1 M.-P. Tu,12 C.-M. Yin,2 R. S. Garofalo3

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.

1 Brown University, Providence, RI 02912, USA.
2 University of Massachusetts, Amherst, MA 01003, USA.
3 Pfizer Global Research and Development, Groton, CT 06340, USA.
*   To whom correspondence should be addressed. E-mail: Marc_Tatar{at}Brown.edu

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Decreased Lifespan in the Absence of Expression of the Mitochondrial Small Heat Shock Protein Hsp22 in Drosophila.
G. Morrow, S. Battistini, P. Zhang, and R. M. Tanguay (2004)
J. Biol. Chem. 279, 43382-43385
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The effect of age on encounters between male crab spiders.
H. H. Hu and D. H. Morse (2004)
Behav. Ecol. 15, 883-888
   Abstract »    Full Text »    PDF »

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