CGC Bibliography Paper 5659

A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity.

Lee SS, Lee RYN, Fraser AG, Kamath RS, Ahringer J, Ruvkun G

Medline:

12447374

Citation:

Nature Genetics 33: 40-48 2003

Type:

ARTICLE

Genes:

age-1 clk-1daf-2 daf-16 lrs-2 unc-29

Abstract:

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.