Biomedical Research Center Seltersberg (BFS) and Dept of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany.
Member of the German Centre for Lung Research (DZL).
Eur Respir Rev. 2020 Jul 7;29(156). doi: 10.1183/16000617.0126-2020. Print 2020 Jun 30.
Healthy ageing of the lung involves structural changes but also numerous cell-intrinsic and cell-extrinsic alterations. Among them are the age-related decline in central cellular quality control mechanisms such as redox and protein homeostasis. In this review, we would like to provide a conceptual framework of how impaired stress responses in the ageing lung, as exemplified by dysfunctional redox and protein homeostasis, may contribute to onset and progression of COPD and idiopathic pulmonary fibrosis (IPF). We propose that age-related imbalanced redox and protein homeostasis acts, amongst others ( cellular senescence), as a "first hit" that challenges the adaptive stress-response pathways of the cell, increases the level of oxidative stress and renders the lung susceptible to subsequent injury and disease. In both COPD and IPF, additional environmental insults such as smoking, air pollution and/or infections then serve as "second hits" which contribute to persistently elevated oxidative stress that overwhelms the already weakened adaptive defence and repair pathways in the elderly towards non-adaptive, irremediable stress thereby promoting development and progression of respiratory diseases. COPD and IPF are thus distinct horns of the same devil, "lung ageing".
肺的健康衰老涉及结构变化，但也有许多内在细胞和外在细胞的改变。其中包括氧化还原和蛋白质动态平衡等中央细胞质量控制机制的年龄相关性下降。在这篇综述中，我们想提供一个概念框架，说明衰老肺中的应激反应受损（例如氧化还原和蛋白质动态平衡功能障碍）如何导致 COPD 和特发性肺纤维化（IPF）的发病和进展。我们提出，与其他因素（如细胞衰老）一样，与年龄相关的不平衡氧化还原和蛋白质动态平衡是一种“第一击”，它挑战了细胞的适应性应激反应途径，增加了氧化应激水平，使肺易受随后的损伤和疾病影响。在 COPD 和 IPF 中，吸烟、空气污染和/或感染等额外的环境损伤充当“第二击”，导致持续升高的氧化应激超过已经减弱的老年适应性防御和修复途径，从而促进呼吸疾病的发展和进展。因此，COPD 和 IPF 是同一个恶魔的不同方面，即“肺衰老”。
