Devulder Justine V
National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
Chin Med J Pulm Crit Care Med. 2024 Sep 17;2(3):133-141. doi: 10.1016/j.pccm.2024.08.007. eCollection 2024 Sep.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by airflow limitation and changes in airway structures that can lead to chronic bronchitis, small airway diseases, and emphysema. COPD is the 3 leading cause of death worldwide and despite current research, there are no curative disease treatments for COPD. As the prevalence of COPD is higher in people over 60 years old than in younger age groups, COPD is considered a condition of accelerated lung aging. Natural lung aging is associated with molecular, cellular, and physiological changes that cause alteration in lung structure, in lung function and regeneration, and decreased immune system response that could lead to lung disease like COPD. Mechanisms of accelerated lung aging are complex and composed by increased oxidative stress induced by exposure to cigarette smoke, by chronic inflammatory processes, and increased number of senescent cells within the airways. Cellular senescence is the cessation of cell division after a finite number of proliferation cycles or in response to cell stressors, such as oxidative stress. Senescent cells show activation of the cell cycle regulators p21 (cyclin-dependent kinase inhibitor-1), p16 (cyclin-dependent kinase inhibitor-2A), and p53 (cellular tumor antigen p53) that lead to cell cycle arrest. Senescent cells exhibit a change in their phenotype and their metabolic activity, along with the production of proinflammatory proteins collectively known as senescence-associated secretory phenotype (SASP). This review aims to describe recent developments in our understanding of aging mechanisms and how the acceleration of lung aging participates in COPD pathophysiology and comorbidities. Understanding and targeting aging mechanisms may result in the development of new therapeutics that could be effective for COPD and also for other age-related diseases.
慢性阻塞性肺疾病（COPD）是一种慢性炎症性肺部疾病，其特征为气流受限以及气道结构改变，可导致慢性支气管炎、小气道疾病和肺气肿。COPD是全球第三大致死原因，尽管目前有相关研究，但尚无治愈COPD的疾病治疗方法。由于60岁以上人群中COPD的患病率高于年轻人群体，COPD被认为是一种加速肺衰老的病症。自然肺衰老与分子、细胞和生理变化相关，这些变化会导致肺结构、肺功能和再生的改变，以及免疫系统反应降低，进而可能引发如COPD等肺部疾病。加速肺衰老的机制复杂，由接触香烟烟雾诱导的氧化应激增加、慢性炎症过程以及气道内衰老细胞数量增加所构成。细胞衰老指的是在有限数量的增殖周期后或对细胞应激源（如氧化应激）作出反应时细胞分裂的停止。衰老细胞表现出细胞周期调节因子p21（细胞周期蛋白依赖性激酶抑制剂-1）、p16（细胞周期蛋白依赖性激酶抑制剂-2A）和p53（细胞肿瘤抗原p53）的激活，从而导致细胞周期停滞。衰老细胞的表型和代谢活性发生变化，同时还会产生统称为衰老相关分泌表型（SASP）的促炎蛋白。本综述旨在描述我们对衰老机制的最新认识进展，以及肺衰老加速如何参与COPD的病理生理学和合并症。理解并针对衰老机制可能会促成新治疗方法的开发，这些方法可能对COPD以及其他与年龄相关的疾病有效。
