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

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

Research output: Contribution to journalArticleAcademicpeer-review

676 Citations (Scopus)
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Abstract

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)722-733
Number of pages12
JournalDevelopmental Cell
Volume31
Issue number6
DOIs
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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