Peer-reviewedCC BYNature Cell Biology
Transcription-independent induction of rapid-onset senescence is integral to healing
18 affiliations
- 1Austrian Cluster for Tissue Regeneration, Vienna, Austria
- 2Institute of Molecular Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria
- 3Ludwig Boltzmann Institute for Traumatology in AUVA Research Center, Vienna, Austria
- 4Ludwig Boltzmann Research Group Senescence and Healing of Wounds, Vienna, Austria
- 5Department of Physiology and Biomedical Engineering and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA
- 6InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Regenerative Biology Team, Olsztyn, Poland
- 7University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
- 8Institut Hospitalo-Universitaire (IHU) RESPIRera and FHU OncoAge, CHU, Nice, France
- 9Université Côte d'Azur, Centre National de la Recherche Scientifique (CNRS) UMR7284, Institut National de la Santé et de la Recherche Médicale (INSERM) U1081, Adipo-Cible Research Study Group, Institute for Research on Cancer and Aging, Nice (IRCAN), Nice, France
- 10Kyiv School of Economics, Kyiv, Ukraine
- 11Research and Development University, Ivano-Frankivsk, Ukraine
- 12Department of Agricultural Sciences, University of Natural Resources and Life Sciences, Vienna, Austria
- 13Institute of In Vivo and In Vitro Models, University of Veterinary Medicine Vienna, Vienna, Austria
- 14Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Vienna, Austria
- 15New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
- 16Austrian Cluster for Tissue Regeneration, Vienna, Austria. [email protected]
- 17Ludwig Boltzmann Institute for Traumatology in AUVA Research Center, Vienna, Austria. [email protected]
- 18Ludwig Boltzmann Research Group Senescence and Healing of Wounds, Vienna, Austria. [email protected]
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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BibTeX
@article{valdivieso2026transcriptionindependent,
title = {{Transcription-independent induction of rapid-onset senescence is integral to healing}},
author = {Karla Valdivieso and Tomaz Rozmaric and Stella G. Victorelli and Vaibhav Jadhav and Nadja Ring and Sylwia Machcińska-Zielińska and Barbara Schädl and Helene Dworak and Eirini Klinaki and Ines Fischer and Agnieszka Gadecka and Iryna Moskalevska and Sara Kostrebic and Michaela Kienberger and Edyta Marzec and Christina Efraimoglou and Alessia Zanchetta and Julien Cherfils‐Vicini and Oleh V. Lushchak and Andreas Löscher and Thomas Kolbe and Maik Dahlhoff and Nicholas Pirius and Aniko Gutasi and Sarolta Takacs and James Ferguson and Bruno K. Podesser and Paul Slezak and David G. Monroe and Bin Zhou and Sundeep Khosla and Johannes Grillari and Heinz R. Redl and Diana Jurk and Mikolaj B. Ogrodnik},
journal = {Nature Cell Biology},
year = {2026},
month = may,
doi = {10.1038/s41556-026-01948-2},
url = {https://doi.org/10.1038/s41556-026-01948-2},
note = {CC BY},
}
RIS
TY - JOUR
TI - Transcription-independent induction of rapid-onset senescence is integral to healing
AU - Karla Valdivieso
AU - Tomaz Rozmaric
AU - Stella G. Victorelli
AU - Vaibhav Jadhav
AU - Nadja Ring
AU - Sylwia Machcińska-Zielińska
AU - Barbara Schädl
AU - Helene Dworak
AU - Eirini Klinaki
AU - Ines Fischer
AU - Agnieszka Gadecka
AU - Iryna Moskalevska
AU - Sara Kostrebic
AU - Michaela Kienberger
AU - Edyta Marzec
AU - Christina Efraimoglou
AU - Alessia Zanchetta
AU - Julien Cherfils‐Vicini
AU - Oleh V. Lushchak
AU - Andreas Löscher
AU - Thomas Kolbe
AU - Maik Dahlhoff
AU - Nicholas Pirius
AU - Aniko Gutasi
AU - Sarolta Takacs
AU - James Ferguson
AU - Bruno K. Podesser
AU - Paul Slezak
AU - David G. Monroe
AU - Bin Zhou
AU - Sundeep Khosla
AU - Johannes Grillari
AU - Heinz R. Redl
AU - Diana Jurk
AU - Mikolaj B. Ogrodnik
PY - 2026
DA - 2026/05/28
JO - Nature Cell Biology
DO - 10.1038/s41556-026-01948-2
UR - https://doi.org/10.1038/s41556-026-01948-2
AB - 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.
SN - 1465-7392
SN - 1476-4679
ER -