TOR signaling couples oxygen sensing to lifespan in C.elegans

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 regulationof the nutrient-sensing kinase target of rapamycin(TOR) and its upstream activator, RHEB-1. The increase in lifespan during hypoxia requires theintestinal 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 isrequired for lifespan under hypoxia. These resultsindicate mitochondrial ROS-dependent TOR signaling integrates metabolic adaptations in order to confer survival under hypoxia.