Oxygen sensing governs tissue regeneration, degeneration, and ageing.

Hypoxia is not simply harmful or protective. Recent studies suggest that hypoxia-inducible factor 1-alpha (HIF-1α) acts as a time- and context-sensitive regulator of tissue-state transitions. We propose that transient HIF-1α activity enables regenerative entry, whereas persistent or unresolved signalling promotes maladaptive remodelling, degeneration, and ageing.