Nature Genetics33, 40 - 48 (2002)
Published online: 25 November 2002; | doi:10.1038/ng1056
A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity
Siu Sylvia Lee1, Raymond Y.N. Lee1, 3, Andrew G. Fraser2, Ravi S. Kamath2, Julie Ahringer2
& Gary Ruvkun1
1
Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
2
Wellcome Trust/Cancer Research UK Institute, University of Cambridge, Cambridge, UK.
3
Present address: WormBase, Division of Biology, California Institute of Technology, Pasadena, California, USA.
We report a systematic RNA interference (RNAi) screen of 5,690 Caenorhabditis elegans genes for gene inactivations that increase lifespan. We found that genes important for mitochondrial function stand out as a principal group of genes affecting C. elegans lifespan. A classical genetic screen identified a mutation in the mitochondrial leucyl-tRNA synthetase gene (lrs-2) that impaired mitochondrial function and was associated with longer-lifespan. The long-lived worms with impaired mitochondria had lower ATP content and oxygen consumption, but differential responses to free-radical and other stresses. These data suggest that the longer lifespan of C. elegans with compromised mitochrondria cannot simply be assigned to lower free radical production and suggest a more complex coupling of metabolism and longevity.
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