A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function |
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Authors: | Tatar M Kopelman A Epstein D Tu M P Yin C M Garofalo R S |
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Institution: | Brown University, Providence, RI 02912, USA., University of Massachusetts, Amherst, MA 01003, USA. Marc_Tatar@Brown.edu |
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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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