Dept of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Program in Immunology, University of Michigan, Ann Arbor, MI, USA.
Eur Respir J. 2020 Dec 24;56(6). doi: 10.1183/13993003.02708-2020. Print 2020 Dec.
Cellular senescence permanently arrests the replication of various cell types and contributes to age-associated diseases. In particular, cellular senescence may enhance chronic lung diseases including COPD and idiopathic pulmonary fibrosis. However, the role cellular senescence plays in the pathophysiology of acute inflammatory diseases, especially viral infections, is less well understood. There is evidence that cellular senescence prevents viral replication by increasing antiviral cytokines, but other evidence shows that senescence may enhance viral replication by downregulating antiviral signalling. Furthermore, cellular senescence leads to the secretion of inflammatory mediators, which may either promote host defence or exacerbate immune pathology during viral infections. In this Perspective article, we summarise how senescence contributes to physiology and disease, the role of senescence in chronic lung diseases, and how senescence impacts acute respiratory viral infections. Finally, we develop a potential framework for how senescence may contribute, both positively and negatively, to the pathophysiology of viral respiratory infections, including severe acute respiratory syndrome due to the coronavirus SARS-CoV-2.
细胞衰老会永久性地阻止各种细胞类型的复制，并导致与年龄相关的疾病。特别是，细胞衰老可能会加重慢性肺部疾病，包括 COPD 和特发性肺纤维化。然而，细胞衰老在急性炎症性疾病（特别是病毒感染）的病理生理学中的作用还不太清楚。有证据表明，细胞衰老通过增加抗病毒细胞因子来阻止病毒复制，但其他证据表明，衰老可能通过下调抗病毒信号来增强病毒复制。此外，细胞衰老会导致炎症介质的分泌，这可能在病毒感染过程中促进宿主防御或加重免疫病理。在这篇观点文章中，我们总结了衰老如何促进生理和疾病、衰老在慢性肺部疾病中的作用，以及衰老如何影响急性呼吸道病毒感染。最后，我们提出了一个潜在的框架，说明衰老如何积极和消极地影响病毒呼吸道感染的病理生理学，包括由冠状病毒 SARS-CoV-2 引起的严重急性呼吸综合征。
