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 VanSteeg, Martijn E.T. Dollé, Jan H.J. Hoeijmakers, Alain deBruin, Eiji Hara, Judith Campisi

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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 amouse model in which senescent cells can be visualized and eliminated in living animals. We show thatsenescent 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). Intwo 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 (US)
Pages (from-to)722-733
Number of pages12
JournalDevelopmental cell
Volume31
Issue number6
DOIs
StatePublished - Dec 22 2014

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ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R. M., Vijg, J., VanSteeg, H., Dollé, M. E. T., Hoeijmakers, J. H. J., deBruin, A., Hara, E., & Campisi, J. (2014). An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Developmental cell, 31(6), 722-733. https://doi.org/10.1016/j.devcel.2014.11.012