An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA

• p16-3MR transgenic mice are a model to study the role of senescence in vivo
• Endothelial and mesenchymal cells undergo senescence during skin wound healing
• Depletion of senescent cells impairs the kinetics of wound closure
• PDGF-AA is a senescence-associated factor essential for optimal wound healing

SummaryCellular 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.

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