| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2042270 | Cell Reports | 2014 | 7 Pages |
•Transient hypoxia extends lifespan in C. elegans through intestinal TOR signaling.•The intestinal transcription factor ELT-2 is required for lifespan extension.•TOR/ELT-2 upregulation of GSTO-1 confers longevity under transient hypoxia.•Mitochondrial ROS are required and sufficient for longevity through TOR and ELT-2.
SummaryMetazoans 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.
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