| Summary: | Summary: Metazoans adapt to a low-oxygen environment (hypoxia) through activation of stress-response pathways. Here, we report that transient hypoxia exposure extends lifespan in C. elegans through mitochondrial reactive oxygen species (ROS)-dependent regulation of the nutrient-sensing kinase target of rapamycin (TOR) and its upstream activator, RHEB-1. The increase in lifespan during hypoxia requires the intestinal GATA-type transcription factor ELT-2 downstream of TOR signaling. Using RNA sequencing (RNA-seq), we describe an ELT-2-dependent hypoxia response that includes an intestinal glutathione S-transferase, GSTO-1, and uncover that GSTO-1 is required for lifespan under hypoxia. These results indicate mitochondrial ROS-dependent TOR signaling integrates metabolic adaptations in order to confer survival under hypoxia. : Metazoans adapt to low-oxygen environments (hypoxia) through activation of stress-response pathways. Schieber and Chandel now report on a hypoxia response that extends lifespan in C. elegans. Under hypoxia, increased levels of mitochondrial ROS upregulate the intestinal glutathione S-transferase GSTO-1 to extend lifespan. The nutrient-signaling kinase TOR and the intestinal GATA-type transcription factor ELT-2 are required for GSTO-1 induction. These results uncover a mechanism for adaptation to hypoxia and support a model whereby increased mitochondrial ROS prevent age-related pathologies.
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