Department of Pathology, University of Verona, Verona, Italy.
Transl Res. 2013 Sep;162(3):156-73. doi: 10.1016/j.trsl.2013.06.004. Epub 2013 Jul 2.
Different anatomic and physiological changes occur in the lung of aging people that can affect pulmonary functions, and different pulmonary diseases, including deadly diseases such as chronic obstructive pulmonary disease (COPD)/emphysema and idiopathic pulmonary fibrosis (IPF), can be related to an acceleration of the aging process. The individual genetic background, as well as exposure to a variety of toxic substances (cigarette smoke in primis) can contribute significantly to accelerating pulmonary senescence. Premature aging can impair lung function by different ways: by interfering specifically with tissue repair mechanisms after damage, thus perturbing the correct crosstalk between mesenchymal and epithelial components; by inducing systemic and/or local alteration of the immune system, thus impairing the complex mechanisms of lung defense against infections; and by stimulating a local and/or systemic inflammatory condition (inflammaging). According to recently proposed pathogenic models in COPD and IPF, premature cellular senescence likely affects distinct progenitors cells (mesenchymal stem cells in COPD, alveolar epithelial precursors in IPF), leading to stem cell exhaustion. In this review, the large amount of data supporting this pathogenic view are discussed, with emphasis on the possible molecular and cellular mechanisms leading to the severe parenchymal remodeling that characterizes, in different ways, these deadly diseases.
衰老人群的肺部会发生不同的解剖和生理变化，这可能会影响肺部功能，并且不同的肺部疾病，包括慢性阻塞性肺疾病（COPD）/肺气肿和特发性肺纤维化（IPF）等致命疾病，都可能与衰老过程的加速有关。个体遗传背景以及接触各种有毒物质（尤其是香烟烟雾）可能会极大地促进肺部衰老。过早衰老会通过不同的方式损害肺功能：通过特异性地干扰损伤后的组织修复机制，从而破坏间质和上皮成分之间的正确串扰；通过诱导全身和/或局部免疫系统的改变，从而损害肺对感染的复杂防御机制；并通过刺激局部和/或全身炎症状态（炎症衰老）。根据 COPD 和 IPF 中最近提出的发病模型，过早的细胞衰老可能会影响不同的祖细胞（COPD 中的间充质干细胞，IPF 中的肺泡上皮前体），导致干细胞耗竭。在这篇综述中，讨论了支持这种发病观点的大量数据，并重点介绍了导致这些致命疾病以不同方式特征性的严重实质重塑的可能分子和细胞机制。
