National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom; email:
Annu Rev Physiol. 2017 Feb 10;79:517-539. doi: 10.1146/annurev-physiol-022516-034314. Epub 2016 Dec 9.
Chronic obstructive pulmonary disease (COPD) is regarded as a disease of accelerated lung aging. This affliction shows all of the hallmarks of aging, including telomere shortening, cellular senescence, activation of PI3 kinase-mTOR signaling, impaired autophagy, mitochondrial dysfunction, stem cell exhaustion, epigenetic changes, abnormal microRNA profiles, immunosenescence, and a low-grade chronic inflammation (inflammaging). Many of these pathways are driven by chronic exogenous and endogenous oxidative stress. There is also a reduction in antiaging molecules, such as sirtuins and Klotho, which further accelerate the aging process. COPD is associated with several comorbidities (multimorbidity), such as cardiovascular and metabolic diseases, that share the same pathways of accelerated aging. Understanding these mechanisms has helped identify several novel therapeutic targets, and several drugs and dietary interventions are now in development to treat multimorbidity.
慢性阻塞性肺疾病（COPD）被认为是一种加速肺部衰老的疾病。这种疾病表现出所有与衰老相关的特征，包括端粒缩短、细胞衰老、PI3K-mTOR 信号通路激活、自噬受损、线粒体功能障碍、干细胞衰竭、表观遗传改变、异常 microRNA 谱、免疫衰老和低度慢性炎症（炎症衰老）。这些途径中的许多都受到慢性外源性和内源性氧化应激的驱动。抗衰分子（如 Sirtuins 和 Klotho）的减少也进一步加速了衰老过程。COPD 与多种合并症（多种疾病）相关，如心血管和代谢疾病，这些疾病具有相同的加速衰老途径。了解这些机制有助于确定几个新的治疗靶点，目前正在开发几种药物和饮食干预措施来治疗多种疾病。
