Regulation of C. elegans Life-Span by Insulinlike Signaling in the Nervous System

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Science  06 Oct 2000:
Vol. 290, Issue 5489, pp. 147-150
DOI: 10.1126/science.290.5489.147

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An insulinlike signaling pathway controlsCaenorhabditis 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-2pathway 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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed: E-mail: ruvkun{at}

  • Present address: Department of Pathology, Harvard Medical School, Boston, MA 02114, USA.

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