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Proc Natl Acad Sci U S A. 2016 May 17;113(20):E2832-41. doi: 10.1073/pnas.1524727113. Epub 2016 May 2.

Roles for ROS and hydrogen sulfide in the longevity response to germline loss in Caenorhabditis elegans.

Author information

1
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158.
2
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158 cynthia@calicolabs.com.

Abstract

In Caenorhabditis elegans, removing germ cells slows aging and extends life. Here we show that transcription factors that extend life and confer protection to age-related protein-aggregation toxicity are activated early in adulthood in response to a burst of reactive oxygen species (ROS) and a shift in sulfur metabolism. Germline loss triggers H2S production, mitochondrial biogenesis, and a dynamic pattern of ROS in specific somatic tissues. A cytoskeletal protein, KRI-1, plays a key role in the generation of H2S and ROS. These kri-1-dependent redox species, in turn, promote life extension by activating SKN-1/Nrf2 and the mitochondrial unfolded-protein response, respectively. Both H2S and, remarkably, kri-1-dependent ROS are required for the life extension produced by low levels of the superoxide-generator paraquat and by a mutation that inhibits respiration. Together our findings link reproductive signaling to mitochondria and define an inducible, kri-1-dependent redox-signaling module that can be invoked in different contexts to extend life and counteract proteotoxicity.

KEYWORDS:

Aβ; KRIT1; Nrf2; SKN-1; hormesis

PMID:
27140632
PMCID:
PMC4878494
DOI:
10.1073/pnas.1524727113
[Indexed for MEDLINE]
Free PMC Article

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