Regulation of C. elegans life-span by insulinlike signaling in the nervous system.

Authors: Wolkow, C A; Kimura, K D; Lee, M S; Ruvkun, G

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.

Keywords: Aging/genetics/*physiology; Animals; Caenorhabditis elegans/genetics/*physiology; *Caenorhabditis elegans Proteins; Catalase/genetics/metabolism; Gene Expression Regulation; Genes, Helminth; Helminth Proteins/genetics/metabolism; Intestines/cytology/physiology; Larva/physiology; Longevity; Muscles/cytology/physiology; Nervous System Physiological Phenomena; Neurons/*physiology; Phenotype; *Phosphatidylinositol 3-Kinases; Promoter Regions, Genetic; Receptor, Insulin/genetics/*metabolism; Recombinant Fusion Proteins/metabolism; *Signal Transduction; Superoxide Dismutase/genetics/metabolism
Journal: Science
Volume: 290
Issue: 5489
Pages: 147-50
Date: Oct. 6, 2000
PMID: 11021802
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Citation:

Wolkow, C A, Kimura, K D, Lee, M S, Ruvkun, G (2000) Regulation of C. elegans life-span by insulinlike signaling in the nervous system. Science 290: 147-50.


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