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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / physiology*
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Alleles
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Animals
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Carrier Proteins / genetics*
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Carrier Proteins / physiology*
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Corpora Allata / metabolism*
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Drosophila Proteins*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / physiology*
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Female
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Fertility
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Genes, Insect
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Genotype
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Insulin / pharmacology
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Juvenile Hormones / metabolism
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Longevity / physiology*
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Male
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Methoprene / pharmacology
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Mutation
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Protein-Tyrosine Kinases / genetics*
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Protein-Tyrosine Kinases / physiology*
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Receptor Protein-Tyrosine Kinases*
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Receptor, Insulin / genetics
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Receptor, Insulin / physiology
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Reproduction
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Signal Transduction
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Superoxide Dismutase / metabolism
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Triglycerides / metabolism
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Vitellogenesis / drug effects
Substances
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Carrier Proteins
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Drosophila Proteins
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Insulin
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Juvenile Hormones
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Triglycerides
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Methoprene
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Superoxide Dismutase
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InR protein, Drosophila
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Protein-Tyrosine Kinases
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Receptor Protein-Tyrosine Kinases
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Receptor, Insulin