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

M Demaria, N Ohtani, SA Youssef, F Rodier… - Developmental cell, 2014 - cell.com
M Demaria, N Ohtani, SA Youssef, F Rodier, W Toussaint, JR Mitchell, RM Laberge, J Vijg…
Developmental cell, 2014cell.com
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 …
Summary
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.
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