M. Tatar et al., A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function, SCIENCE, 292(5514), 2001, pp. 107-110
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 mal
es with reduced Late age-specific mortality. Treatment of the Long-lived In
R dwarfs with a juvenile hormone analog restores Life expectancy toward tha
t of wild-type controls. We conclude that juvenile hormone deficiency, whic
h results from InR signal pathway mutation, is sufficient to extend life-sp
an, and that in flies, insulin-like Ligands nonautonomously mediate aging t
hrough retardation of growth or activation of specific endocrine tissue.