A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function

• Published in: Science (American Association for the Advancement of Science) Vol. 292; no. 5514; pp. 107 - 110
• Main Authors: Tatar, M., Kopelman, A., Epstein, D., M.-P. Tu, C.-M. Yin, Garofalo, R. S.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 06-04-2001; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Adults; Aging - physiology; Alleles; Animals; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - physiology; Cell physiology; Corpora Allata - metabolism; Diapause; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - physiology; Drosophila Proteins; Eclosion; Female; Female animals; Fertility; Fruit-flies; Fundamental and applied biological sciences. Psychology; Genes; Genes, Insect; Genotype; Genotypes; Growth; Histones; Hormones; Insects; Insulin; Insulin - pharmacology; Juvenile Hormones - metabolism; Life expectancy; Life sciences; Longevity; Longevity - physiology; Male; Methoprene - pharmacology; Molecular and cellular biology; Mutation; Physiological aspects; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - physiology; Receptor Protein-Tyrosine Kinases; Receptor, Insulin - genetics; Receptor, Insulin - physiology; Receptors; Reproduction; Signal Transduction; Superoxide Dismutase - metabolism; Triglycerides - metabolism; Vitellogenesis - drug effects; Worms; United States; Insecta; Homology; Longevity; Insulin; Drosophilidae; Signal transduction; Gene; Arthropoda; Mutation; Invertebrata; Drosophila melanogaster; Diptera; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1057987

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.