Abstract
An insulinlike signaling pathway controls Caenorhabditis elegans aging, metabolism, and development. Mutations in the daf-2 insulin receptor-like gene or the downstream age-1 phosphoinositide 3-kinase gene extend adult life-span by two- to threefold. To identify tissues where this pathway regulates aging and metabolism, we restored daf-2 pathway signaling to only neurons, muscle, or intestine. Insulinlike signaling in neurons alone was sufficient to specify wild-type life-span, but muscle or intestinal signaling was not. However, restoring daf-2 pathway signaling to muscle rescued metabolic defects, thus decoupling regulation of life-span and metabolism. These findings point to the nervous system as a central regulator of animal longevity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / genetics
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Aging / physiology*
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Animals
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins*
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Catalase / genetics
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Catalase / metabolism
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Gene Expression Regulation
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Genes, Helminth
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Helminth Proteins / genetics
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Helminth Proteins / metabolism
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Intestines / cytology
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Intestines / physiology
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Larva / physiology
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Longevity
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Muscles / cytology
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Muscles / physiology
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Nervous System Physiological Phenomena
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Neurons / physiology*
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Phenotype
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Phosphatidylinositol 3-Kinases*
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Promoter Regions, Genetic
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Receptor, Insulin / genetics
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Receptor, Insulin / metabolism*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction*
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism
Substances
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Caenorhabditis elegans Proteins
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Helminth Proteins
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Recombinant Fusion Proteins
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Catalase
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Superoxide Dismutase
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Phosphatidylinositol 3-Kinases
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AGE-1 protein, C elegans
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DAF-2 protein, C elegans
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Receptor, Insulin