Abstract

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.

Public Health Relevance

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG016636-15
Application #
8514458
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Guo, Max
Project Start
1999-04-01
Project End
2016-05-31
Budget Start
2013-09-01
Budget End
2014-05-31
Support Year
15
Fiscal Year
2013
Total Cost
$501,742
Indirect Cost
$213,384

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

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
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
Wu, Xiaoyun; Shi, Zhen; Cui, Mingxue et al. (2012) Repression of germline RNAi pathways in somatic cells by retinoblastoma pathway chromatin complexes. PLoS Genet 8:e1002542

Showing the most recent 10 out of 19 publications