Zhang Tingwei, Zhang Jinjin, Lv Changjun, Li Hongbo, Song Xiaodong
Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.
Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.
Front Pharmacol. 2022 Nov 15;13:1059434. doi: 10.3389/fphar.2022.1059434. eCollection 2022.
Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal lung disease with limited treatment options. The onset of IPF increases with age, indicating that aging is a major risk factor for IPF. Among the hallmarks of aging, cellular senescence is the primordial driver and primary etiological factor for tissue and organ aging, and an independent risk factor for the progression of IPF. In this review, we focus on the senescence of alveolar type II epithelial cells (AECIIs) and systematically summarize abnormal changes in signal pathways and biological process and implications of senescent AECIIs during IPF progression. Meanwhile, we objectively analyze current medications targeting the elimination of senescent cells or restoration of vitality such as senolytics, senomorphics, autophagy regulators, and stem cell therapy. Finally, we dialectically discuss the feasibility and limitation of targeting senescent AECIIs for IPF treatment. We hope that the understanding will provide new insights to the development of senescent AECII-based approaches for the prevention and mitigation of IPF.
特发性肺纤维化（IPF）是一种慢性致命性肺部疾病，治疗选择有限。IPF的发病率随年龄增长而增加，这表明衰老 是IPF的主要危险因素。在衰老的特征中，细胞衰老 是组织和器官衰老的主要驱动因素和主要病因，也是IPF进展的独立危险因素。在这篇综述中，我们聚焦于II型肺泡上皮细胞（AECIIs）的衰老，系统总结了IPF进展过程中信号通路和生物学过程的异常变化以及衰老AECIIs的影响。同时，我们客观分析了当前针对消除衰老细胞或恢复活力的药物，如衰老细胞溶解剂、衰老细胞形态调节剂、自噬调节剂和干细胞疗法。最后，我们辩证地讨论了针对衰老AECIIs治疗IPF的可行性和局限性。我们希望这一认识将为开发基于衰老AECIIs的预防和缓解IPF的方法提供新的见解。
