title: An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.
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.
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Demaria
authors.affiliation: Division of Cancer Biology, The Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ohtani
authors.affiliation: Department of Pathobiology, Dutch Molecular Pathology Center, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3509, the Netherlands.
authors.forename: Sameh A
authors.initials: SA
authors.lastname: Youssef
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Rodier
authors.affiliation: CGC Department of Genetics, Erasmus Medical Center, Rotterdam 12306, the Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Toussaint
authors.affiliation: CGC Department of Genetics, Erasmus Medical Center, Rotterdam 12306, the Netherlands.
authors.forename: James R
authors.initials: JR
authors.lastname: Mitchell
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors.forename: Remi-Martin
authors.initials: RM
authors.lastname: Laberge
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Vijg
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Leiden 2318 NN, the Netherlands; National Institute of Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, Bilthoven 3721 MA, the Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Van Steeg
authors.affiliation: National Institute of Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, Bilthoven 3721 MA, the Netherlands.
authors.forename: Martijn E T
authors.initials: ME
authors.lastname: Dollé
authors.affiliation: CGC Department of Genetics, Erasmus Medical Center, Rotterdam 12306, the Netherlands.
authors.forename: Jan H J
authors.initials: JH
authors.lastname: Hoeijmakers
authors.affiliation: Department of Pathobiology, Dutch Molecular Pathology Center, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3509, the Netherlands.
authors.forename: Alain
authors.initials: A
authors.lastname: de Bruin
authors.affiliation: Division of Cancer Biology, The Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Hara
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA; Lawrence Berkeley National Laboratory, Life Sciences Division, 1 Cyclotron Road, Berkeley, CA 94720, USA. Electronic address: jcampisi@lbl.gov.
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D016922:Cellular Senescence; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D049449:Luminescence; D008297:Male; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D058628:Myofibroblasts / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000378:metabolism*; D019076:Transgenes; D014945:Wound Healing
chemical_list: D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A