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.

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
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Lehrbach, Nicolas J; Ruvkun, Gary (2016) Proteasome dysfunction triggers activation of SKN-1A/Nrf1 by the aspartic protease DDI-1. Elife 5:
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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

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