Cellular Senescence in Acute and Chronic Wound Repair

Wilkinson, Holly N.; Hardman, Matthew J.

Abstract

Cellular senescence, once thought an artifact of in vitro culture or passive outcome of aging, has emerged as fundamental to tissue development and function. The senescence mechanism importantly halts cell cycle progression to protect against tumor formation, while transiently present senescent cells produce a complex secretome (or SASP) of inflammatory mediators, proteases, and growth factors that guide developmental remodeling and tissue regeneration. Transiently present senescence is important for skin repair, where it accelerates extracellular matrix formation, limits fibrosis, promotes reepithelialization, and modulates inflammation. Unfortunately, advanced age and diabetes drive pathological accumulation of senescent cells in chronic wounds, which is perpetuated by a proinflammatory SASP, advanced glycation end-products, and oxidative damage. Although the biology of wound senescence remains incompletely understood, drugs that selectively target senescent cells are showing promise in clinical trials for diverse pathological conditions. It may not be long before senescence-targeted therapies will be available for the management, or perhaps even prevention, of chronic wounds.

Citation

Wilkinson, H. N., & Hardman, M. J. (2022). Cellular Senescence in Acute and Chronic Wound Repair. Cold Spring Harbor Perspectives in Biology, 14(11), Article a041221. https://doi.org/10.1101/cshperspect.a041221

• Journal Article Type: Article
• Acceptance Date: Jan 6, 2022
• Online Publication Date: Jul 11, 2022
• Publication Date: Nov 1, 2022
• Deposit Date: Sep 2, 2024
• Publicly Available Date: Sep 27, 2024
• Journal: Cold Spring Harbor Perspectives in Biology
• Electronic ISSN: 1943-0264
• Publisher: Cold Spring Harbor Laboratory Press
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 11
• Article Number: a041221
• DOI: https://doi.org/10.1101/cshperspect.a041221
• Public URL: https://hull-repository.worktribe.com/output/4132708