A systematic RNAi screen for longevity genes in C. elegans.
We report here the first genome-wide functional genomic screen for longevity genes. We systematically surveyed Caenorhabditis elegans genes using large-scale RNA interference (RNAi), and found that RNAi inactivation of 89 genes extend C. elegans lifespan. Components of the daf-2/insulin-like signaling pathway are recovered, as well as genes that regulate metabolism, signal transduction, protein turnover, and gene expression. Many of these candidate longevity genes are conserved across animal phylogeny. Genetic interaction analyses with the new longevity genes indicate that some act upstream of the daf-16/FOXO transcription factor or the sir2.1 protein deacetylase, and others function independently of daf-16/FOXO and sir2.1, and might define new pathways to regulate lifespan.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA.
Benjamin
B
Hamilton
Yuqing
Y
Dong
Mami
M
Shindo
Wenyu
W
Liu
Ian
I
Odell
Gary
G
Ruvkun
Siu Sylvia
SS
Lee
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D008136:Longevity / Q000235:genetics*; D034622:RNA Interference