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
Nature genetics, 2003 volume 33 no. 1 pp 40 - 48
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.
