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Originally published in Science Express on 5 December 2002
Science 20 December 2002:
Vol. 298. no. 5602, pp. 2398 - 2401
DOI: 10.1126/science.1077780
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Reports

Rates of Behavior and Aging Specified by Mitochondrial Function During Development

Andrew Dillin,1* Ao-Lin Hsu,1 Nuno Arantes-Oliveira,1dagger Joshua Lehrer-Graiwer,1 Honor Hsin,1ddagger Andrew G. Fraser,2 Ravi S. Kamath,2 Julie Ahringer,2 Cynthia Kenyon1§

To explore the role of mitochondrial activity in the aging process, we have lowered the activity of the electron transport chain and adenosine 5'-triphosphate (ATP) synthase with RNA interference (RNAi) in Caenorhabditis elegans. These perturbations reduced body size and behavioral rates and extended adult life-span. Restoring messenger RNA to near-normal levels during adulthood did not elevate ATP levels and did not correct any of these phenotypes. Conversely, inhibiting respiratory-chain components during adulthood only did not reset behavioral rates and did not affect life-span. Thus, the developing animal appears to contain a regulatory system that monitors mitochondrial activity early in life and, in response, establishes rates of respiration, behavior, and aging that persist during adulthood.

1 Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0448, USA.
2 Wellcome/CRC Institute, University of Cambridge, Tennis Court Road, Cambridge CB21QR,  UK.
*   Present address: The Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, La Jolla, CA 92037, USA.

dagger    Present address: IN+ Center for Innovation, Technology and Policy Research Instituto Superior Técnico, Technical University of Lisbon 1049-001, Lisbon, Portugal.

ddagger    Present address: Harvard University, Cambridge, MA 02115, USA.

§   To whom correspondence should be addressed. E-mail: ckenyon{at}biochem.ucsf.edu

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