title: Roles for ROS and hydrogen sulfide in the longevity response to germline loss in Caenorhabditis elegans.
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.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158 cynthia@calicolabs.com.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kenyon
mesh_terms: D021581:Active Transport, Cell Nucleus; D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005854:Germ Cells / Q000502:physiology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008136:Longevity; D063154:Mitochondrial Dynamics; D001678:Organelle Biogenesis; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C517777:KRI-1 protein, C elegans; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C073702:skn-1 protein, C elegans; D006862:Hydrogen Sulfide
keywords: Aβ; KRIT1; Nrf2; SKN-1; hormesis