Authors:
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
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.
Source:
Developmental Cell; Vol. 31, Issue 6, 722-733 (12/22/14)