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

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.