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Dev Cell. 2014 Dec 22;31(6):722-33. doi: 10.1016/j.devcel.2014.11.012. Epub 2014 Dec 11.

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

Author information

1
Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
2
Division of Cancer Biology, The Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
3
Department of Pathobiology, Dutch Molecular Pathology Center, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3509, the Netherlands.
4
CGC Department of Genetics, Erasmus Medical Center, Rotterdam 12306, the Netherlands.
5
Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
6
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.
7
National Institute of Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, Bilthoven 3721 MA, the Netherlands.
8
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.

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.

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PMID:
25499914
PMCID:
PMC4349629
DOI:
10.1016/j.devcel.2014.11.012
[Indexed for MEDLINE]
Free PMC Article

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