Publication

An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA

Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., Hoeijmakers, J. H. J., de Bruin, A., Hara, E. & Campisi, J., 22-Dec-2014, In : Developmental Cell. 31, 6, p. 722-33 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Marco Demaria
  • Naoko Ohtani
  • Sameh A Youssef
  • Francis Rodier
  • Wendy Toussaint
  • James R Mitchell
  • Remi-Martin Laberge
  • Jan Vijg
  • Harry Van Steeg
  • Martijn E T Dollé
  • Jan H J Hoeijmakers
  • Alain de Bruin
  • Eiji Hara
  • Judith Campisi

Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s) of the complex senescent phenotype, we generated a mouse model in which senescent cells can be visualized and eliminated in living animals. We show that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In two mouse models, topical treatment of senescence-free wounds with recombinant PDGF-AA rescued the delayed wound closure and lack of myofibroblast differentiation. These findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP evolved.

Original languageEnglish
Pages (from-to)722-33
Number of pages12
JournalDevelopmental Cell
Volume31
Issue number6
Publication statusPublished - 22-Dec-2014

    Keywords

  • Animals, Apoptosis, Cell Aging, Cell Differentiation, Endothelial Cells, Female, Fibroblasts, Luminescence, Male, Mesoderm, Mice, Mice, Transgenic, Myofibroblasts, Platelet-Derived Growth Factor, Transgenes, Wound Healing

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