From a combination of genetic analyses and RNAi screening, we have discovered hundreds of gene inactivations and mutations that regulate C. elegans lifespan. We propose to GFP tag these genes to discern their molecular identity as well as to delineate from their expression pattern which cells mediate the regulation of aging. We will determine the cellular focus of gene activity for aging and whether any of the genes encode proteins that mediate the signaling cellular stress in those cells. C. elegans is amenable to large scale genetic and functional genomic screens which is not feasible in mice. Our worm genomics highlights scores of human genes which are homologues of the worm genes we have identified. In some cases, the genes encode proteins that are attractive for the development of drugs. Therefore, identification of aging pathway genes in C. elegans provides targets for intervention of human aging.
We have discovered hundreds of gene inactivations and mutations that regulate C. elegans lifespan. We will delineate from their expression pattern which cells mediate the regulation of aging. We will determine which of these gene inactivations affect stress signaling pathways. Identification of aging pathway genes in C. elegans provides targets for intervention of human aging.
| Lehrbach, Nicolas J; Ji, Fei; Sadreyev, Ruslan (2017) Next-Generation Sequencing for Identification of EMS-Induced Mutations in Caenorhabditis elegans. Curr Protoc Mol Biol 117:7.29.1-7.29.12 |
| Lehrbach, Nicolas J; Ruvkun, Gary (2016) Proteasome dysfunction triggers activation of SKN-1A/Nrf1 by the aspartic protease DDI-1. Elife 5: |
| Samuel, Buck S; Rowedder, Holli; Braendle, Christian et al. (2016) Caenorhabditis elegans responses to bacteria from its natural habitats. Proc Natl Acad Sci U S A 113:E3941-9 |
| Govindan, J Amaranath; Jayamani, Elamparithi; Zhang, Xinrui et al. (2015) Lipid signalling couples translational surveillance to systemic detoxification in Caenorhabditis elegans. Nat Cell Biol 17:1294-303 |
| Kirienko, Natalia V; Ausubel, Frederick M; Ruvkun, Gary (2015) Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 112:1821-6 |
| Wang, Meng C; Oakley, Holly D; Carr, Christopher E et al. (2014) Gene pathways that delay Caenorhabditis elegans reproductive senescence. PLoS Genet 10:e1004752 |
| Riedel, Christian G; Dowen, Robert H; Lourenco, Guinevere F et al. (2013) DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity. Nat Cell Biol 15:491-501 |
| Shore, David E; Ruvkun, Gary (2013) A cytoprotective perspective on longevity regulation. Trends Cell Biol 23:409-20 |
| Tacutu, Robi; Shore, David E; Budovsky, Arie et al. (2012) Prediction of C. elegans longevity genes by human and worm longevity networks. PLoS One 7:e48282 |
| Shore, David E; Carr, Christopher E; Ruvkun, Gary (2012) Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways. PLoS Genet 8:e1002792 |
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