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.
Tatar
M
M
Brown University, Providence, RI 02912, USA., University of Massachusetts, Amherst, MA 01003, USA. Marc_Tatar@Brown.edu
Kopelman
A
A
Epstein
D
D
Tu
M P
MP
Yin
C M
CM
Garofalo
R S
RS
D000375:Aging / Q000502:physiology*; D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D003335:Corpora Allata / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005260:Female; D005298:Fertility; D017344:Genes, Insect; D005838:Genotype; D007328:Insulin / Q000494:pharmacology; D007605:Juvenile Hormones / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D008297:Male; D008726:Methoprene / Q000494:pharmacology; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology; D012098:Reproduction; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014818:Vitellogenesis / Q000187:drug effects
D002352:Carrier Proteins; D029721:Drosophila Proteins; D007328:Insulin; D007605:Juvenile Hormones; D014280:Triglycerides; D008726:Methoprene; D013482:Superoxide Dismutase; C094982:InR protein, Drosophila; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D011972:Receptor, Insulin