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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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