The nematode C. elegans has been a discovery engine for regulation of animal lifespan. We propose to follow up our surprising discovery that decreases in insulin-like signaling induce a dramatic increase in lifespan in C. elegans that is intimately associated with expression of germline-specific pathways in the somatic cells. We will dissect how these genes are regulated by insulin-like signaling and how the somatic expression of germline genes contributes to the increase in longevity. Because essentially all of the genes proposed to be studied in this proposal are conserved in humans, and because the insulin pathway has already been shown to act in human longevity, the pathways we dissect are likely to be applicable to human longevity.
The nematode C. elegans has been a discovery engine for regulation of animal lifespan. Because essentially all of the genes proposed to be studied in this proposal are conserved in humans, and because the insulin pathway has already been shown to act in human longevity, the pathways we dissect are likely to be applicable to human longevity.
| 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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