3rd Respiratory Medicine Department, Sismanogleio General Hospital, Athens, Greece.
Curr Drug Targets. 2013 Feb;14(2):149-57. doi: 10.2174/1389450111314020003.
Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging. The prevalence of COPD is age-dependent suggesting an intimate relationship between the pathogenesis of COPD and aging. Lung function decline, the hallmark feature of COPD evolution, is more prominent with increasing age and this decline is greater in smoking individuals. One of the major goals of COPD pharmacotherapy is the development of drugs that would be able to result in a decrease of the decline in lung function over years. However, till nowadays smoking cessation is the only known intervention which is able to decelerate lung function decline. Several mechanisms of aging, including oxidative stress, inflammation and telomere shortening have been shown to be implicated in COPD. Furthermore, numerous anti-aging molecules, including sirtuins and Nrf-2 are reduced, and pathways such as mTOR and genes such as Klotho have also been shown to be abnormal in the lungs of COPD patients. The above mechanisms have been associated with the accelerated lung aging in COPD patients. Numerous therapeutic interventions have been studied in an attempt to reverse accelerated lung aging, and some of them have already been tested in clinical trials. The aim of the present review is to summarize the mechanisms associated with the accelerated lung aging in COPD and to provide information about the possible therapeutic implications targeting those mechanisms.
慢性阻塞性肺疾病（COPD）最近被描述为一种加速肺衰老的疾病。COPD 的患病率与年龄有关，这表明 COPD 的发病机制与衰老之间存在密切关系。肺功能下降是 COPD 演变的标志性特征，随着年龄的增长，肺功能下降更为明显，而在吸烟人群中更为明显。COPD 药物治疗的主要目标之一是开发能够降低多年来肺功能下降的药物。然而，到目前为止，戒烟是唯一已知的能够减缓肺功能下降的干预措施。包括氧化应激、炎症和端粒缩短在内的几种衰老机制已被证明与 COPD 有关。此外，许多抗衰老分子，包括沉默调节蛋白和 Nrf-2 减少，以及 mTOR 途径和 Klotho 等基因也被证明在 COPD 患者的肺部异常。上述机制与 COPD 患者的加速肺衰老有关。已经研究了许多治疗干预措施，试图逆转加速的肺衰老，其中一些已经在临床试验中进行了测试。本综述的目的是总结与 COPD 加速肺衰老相关的机制，并提供有关针对这些机制的可能治疗意义的信息。
