Airway epithelium senescence as a driving mechanism in COPD pathogenesis

Georgia Bateman, Hong Guo-Parke, Aoife M. Rodgers, Dermot Linden, Melanie Bailey, Sinéad Weldon, Joseph C. Kidney, Clifford C. Taggart*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)
80 Downloads (Pure)

Abstract

Cellular senescence is a state of permanent cell cycle arrest triggered by various intrinsic and extrinsic stressors. Cellular senescence results in impaired tissue repair and remodeling, loss of physiological integrity, organ dysfunction, and changes in the secretome. The systemic accumulation of senescence cells has been observed in many age-related diseases. Likewise, cellular senescence has been implicated as a risk factor and driving mechanism in chronic obstructive pulmonary disease (COPD) pathogenesis. Airway epithelium exhibits hallmark features of senescence in COPD including activation of the p53/p21WAF1/CIP1 and p16INK4A/RB pathways, leading to cell cycle arrest. Airway epithelial senescent cells secrete an array of inflammatory mediators, the so-called senescence-associated secretory phenotype (SASP), leading to a persistent low-grade chronic inflammation in COPD. SASP further promotes senescence in an autocrine and paracrine manner, potentially contributing to the onset and progression of COPD. In addition, cellular senescence in COPD airway epithelium is associated with telomere dysfunction, DNA damage, and oxidative stress. This review discusses the potential mechanisms of airway epithelial cell senescence in COPD, the impact of cellular senescence on the development and severity of the disease, and highlights potential targets for modulating cellular senescence in airway epithelium as a potential therapeutic approach in COPD.

Original languageEnglish
Article number2072
Number of pages14
JournalBiomedicines
Volume11
Issue number7
DOIs
Publication statusPublished - 23 Jul 2023

Bibliographical note

Funding Information:
This work was funded by the Medical Research Council (MR/X001504/1) (CT), Northern Ireland chest heart and stoke (NICHS 2021_C02) (JK), Mater Hospital Young Philanthropist (YP) trustees (JK), Pfizer UK (CT/JK), Chiesi Farmaceutici (CT/JK) and the Department for the Economy PhD studentship (GB/CT).

Publisher Copyright:
© 2023 by the authors.

Keywords

  • airway epithelial cells
  • cellular senescence
  • COPD
  • pathogenesis
  • SASP

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology

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