title: A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity.
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.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Siu Sylvia
authors.initials: SS
authors.lastname: Lee
authors.forename: Raymond Y N
authors.initials: RY
authors.lastname: Lee
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Fraser
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Kamath
authors.forename: Julie
authors.initials: J
authors.lastname: Ahringer
authors.forename: Gary
authors.initials: G
authors.lastname: Ruvkun
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D017238:Genes, Helminth / Q000235:genetics*; D005820:Genetic Testing; D007935:Leucine-tRNA Ligase / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption; D034622:RNA Interference; D013312:Stress, Physiological / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D007935:Leucine-tRNA Ligase