Transcription-independent induction of rapid-onset senescence is integral to healing

Cellular senescence plays key roles in tissue repair, tumour suppression and ageing. Here we identify a rapid, transcription‑independent senescence response in skin following injury. Within minutes to hours after wounding, skin cells at the edge of injury display hallmark features of senescence. This response involves the utilization of pre‑existing Cdkn1a mRNA through the removal of nuclear export inhibitors, which enables Cdkn1a transcript translation and rapid p21 protein accumulation. These cells enter stable cell‑cycle arrest and secrete pro‑migratory and pro‑inflammatory factors that promote tissue repair, including re‑epithelialization. Experimental suppression of this rapid senescence, either genetically or pharmacologically, markedly delays wound closure, whereas inhibition during later phases of repair has no effect. Our findings establish rapid‑onset senescence as a mechanistic requirement for efficient tissue regeneration.