Department of Pulmonology, ICR, Hospital Clinic, 08036 Barcelona, Spain.
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.
Int J Mol Sci. 2021 Jun 29;22(13):7012. doi: 10.3390/ijms22137012.
Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung parenchyma. Over the past years, significant progress has been made in our incomplete understanding of the pathobiology underlying fibrosing ILDs, in particular in relation to diverse age-related processes and cell perturbations that seem to lead to maladaptation to stress and susceptibility to lung fibrosis. Growing evidence suggests that a specific biological phenomenon known as cellular senescence plays an important role in the initiation and progression of pulmonary fibrosis. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. However, recent evidence strengthens the idea that it also drives degenerative processes such as lung fibrosis, most likely by promoting molecular and cellular changes in chronic fibrosing processes. Here, we review how cellular senescence may contribute to lung fibrosis pathobiology, and we highlight current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence.
纤维性间质性肺疾病（ILDs）是一种慢性的、最终致命的与年龄相关的肺部疾病，其特征是肺实质中进行性和不可逆转的瘢痕组织积累。在过去的几年中，我们对纤维性ILDs 基础病理生物学的认识取得了重大进展，特别是在与各种与年龄相关的过程和细胞扰动有关的方面，这些似乎导致了对压力的适应不良和易患肺纤维化。越来越多的证据表明，一种称为细胞衰老的特定生物学现象在肺纤维化的发生和进展中起着重要作用。细胞衰老被定义为由于不可修复的细胞损伤积累而导致的细胞命运决定，其特征是丰富的促炎和促纤维化的分泌组。衰老反应已被广泛认为是发育过程中和肿瘤抑制中的一种有益的生理机制。然而，最近的证据加强了这样一种观点，即它也可能通过促进慢性纤维化过程中的分子和细胞变化来驱动退行性过程，如肺纤维化。在这里，我们回顾了细胞衰老如何可能导致肺纤维化的病理生物学，并强调了当前和新兴的通过靶向细胞衰老来治疗纤维性间质性肺疾病的治疗方法。
