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

Karla Valdivieso, Tomaz Rozmaric, Stella Victorelli, Vaibhav Jadhav, Nadja Anneliese Ruth Ring, Sylwia Machcińska-Zielińska, Barbara Schädl, Helene Dworak, Eirini Klinaki, Ines Fischer, Agnieszka Gadecka, Iryna Moskalevska, Sara Kostrebic, Michaela Kienberger, Edyta Marzec, Christina Efraimoglou, Alessia Zanchetta, Julien Cherfils-Vicini, Oleh Lushchak, Andreas Löscher, Thomas Kolbe, Maik Dahlhoff, Nicholas E Pirius, Aniko Gutasi, Sarolta Takacs, James Ferguson, Bruno K Podesser, Paul Slezak, David Monroe, Bin Zhou, Sundeep Khosla, Johannes Grillari, Heinz Redl, Diana Jurk, Mikolaj Ogrodnik

Ludwig Boltzmann Research Group Senescence and Healing of Wounds, Vienna, Austria. · pubmed

Paper

Abstract

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.

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Research summary

The paper claims that rapid-onset senescence is essential for efficient tissue regeneration following injury. This research is relevant as it explores a mechanism that could influence aging processes and tissue repair, potentially addressing root causes of age-related decline in regenerative capacity.

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