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A systematic RNAi screen for longevity genes in C. elegans

2005; Cold Spring Harbor Laboratory Press; Volume: 19; Issue: 13 Linguagem: Inglês

10.1101/gad.1308205

1549-5477

B. Wade Hamilton, Yuqing Dong, Mami Shindo, Wenyu Liu, Ian D. Odell, Gary Ruvkun, Siu Sylvia Lee,

Genomics, phytochemicals, and oxidative stress

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.