Bateman Georgia, Guo-Parke Hong, Rodgers Aoife M, Linden Dermot, Bailey Melanie, Weldon Sinéad, Kidney Joseph C, Taggart Clifford C
Airway Innate Immunity Research Group, Wellcome Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast BT9 7AE, UK.
Department of Respiratory Medicine, Mater Hospital Belfast, Belfast BT14 6AB, UK.
Biomedicines. 2023 Jul 23;11(7):2072. doi: 10.3390/biomedicines11072072.
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.
细胞衰老 是一种由各种内在和外在应激源触发的永久性细胞周期停滞状态。细胞衰老导致组织修复和重塑受损、生理完整性丧失、器官功能障碍以及分泌组的变化。在许多与年龄相关的疾病中都观察到衰老细胞的系统性积累。同样，细胞衰老被认为是慢性阻塞性肺疾病（COPD）发病机制中的一个危险因素和驱动机制。在COPD中，气道上皮表现出衰老的标志性特征，包括p53/p21WAF1/CIP1和p16INK4A/RB通路的激活，导致细胞周期停滞。气道上皮衰老细胞分泌一系列炎症介质，即所谓的衰老相关分泌表型（SASP），导致COPD中持续的低度慢性炎症。SASP以自分泌和旁分泌方式进一步促进衰老，可能导致COPD的发生和进展。此外，COPD气道上皮中的细胞衰老与端粒功能障碍、DNA损伤和氧化应激有关。本综述讨论了COPD气道上皮细胞衰老的潜在机制、细胞衰老对疾病发展和严重程度的影响，并强调了调节气道上皮细胞衰老作为COPD潜在治疗方法的潜在靶点。
