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Science 290 (5489): 147-150

Copyright © 2000 by the American Association for the Advancement of Science

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

Catherine A. Wolkow,1* Koutarou D. Kimura,2* Ming-Sum Lee,1 † Gary Ruvkun1ddagger

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.

1 Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
2 Division of Biological Science, Nagoya University, Nagoya 464-8602, Japan
*   These authors contributed equally to this work.

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

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