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

Marco Demaria; Naoko Ohtani; Sameh A. Youssef; Francis Rodier; Wendy Toussaint; James R. Mitchell; Remi Martin Laberge; Jan Vijg; Harry VanSteeg; Martijn E.T. Dollé; Jan H.J. Hoeijmakers; Alain deBruin; Eiji Hara; Judith Campisi

doi:10.1016/j.devcel.2014.11.012

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

Marco Demaria, Naoko Ohtani, Sameh A. Youssef, Francis Rodier, Wendy Toussaint, James R. Mitchell, Remi Martin Laberge, Jan Vijg, Harry VanSteeg, Martijn E.T. Dollé, Jan H.J. Hoeijmakers, Alain deBruin, Eiji Hara, Judith Campisi

Genetics

Research output: Contribution to journal › Article › peer-review

1242 Scopus citations

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 amouse model in which senescent cells can be visualized and eliminated in living animals. We show thatsenescent 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). Intwo 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.

Original language	English (US)
Pages (from-to)	722-733
Number of pages	12
Journal	Developmental cell
Volume	31
Issue number	6
DOIs	https://doi.org/10.1016/j.devcel.2014.11.012
State	Published - Dec 22 2014

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.devcel.2014.11.012

Cite this

Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R. M., Vijg, J., VanSteeg, H., Dollé, M. E. T., Hoeijmakers, J. H. J., deBruin, A., Hara, E., & Campisi, J. (2014). An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Developmental cell, 31(6), 722-733. https://doi.org/10.1016/j.devcel.2014.11.012

@article{c515fac6690c4c9e8528802695752fc2,

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 amouse model in which senescent cells can be visualized and eliminated in living animals. We show thatsenescent 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). Intwo 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.",

author = "Marco Demaria and Naoko Ohtani and Youssef, {Sameh A.} and Francis Rodier and Wendy Toussaint and Mitchell, {James R.} and Laberge, {Remi Martin} and Jan Vijg and Harry VanSteeg and Doll{\'e}, {Martijn E.T.} and Hoeijmakers, {Jan H.J.} and Alain deBruin and Eiji Hara and Judith Campisi",

note = "Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",

year = "2014",

month = dec,

day = "22",

doi = "10.1016/j.devcel.2014.11.012",

language = "English (US)",

volume = "31",

pages = "722--733",

journal = "Developmental cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA

AU - Demaria, Marco

AU - Ohtani, Naoko

AU - Youssef, Sameh A.

AU - Rodier, Francis

AU - Toussaint, Wendy

AU - Mitchell, James R.

AU - Laberge, Remi Martin

AU - Vijg, Jan

AU - VanSteeg, Harry

AU - Dollé, Martijn E.T.

AU - Hoeijmakers, Jan H.J.

AU - deBruin, Alain

AU - Hara, Eiji

AU - Campisi, Judith

PY - 2014/12/22

Y1 - 2014/12/22

N2 - 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 amouse model in which senescent cells can be visualized and eliminated in living animals. We show thatsenescent 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). Intwo 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.

AB - 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 amouse model in which senescent cells can be visualized and eliminated in living animals. We show thatsenescent 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). Intwo 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.

UR - http://www.scopus.com/inward/record.url?scp=84919480323&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919480323&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2014.11.012

DO - 10.1016/j.devcel.2014.11.012

M3 - Article

C2 - 25499914

AN - SCOPUS:84919480323

SN - 1534-5807

VL - 31

SP - 722

EP - 733

JO - Developmental cell

JF - Developmental cell

IS - 6

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this