Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang 453007, China.
State Key Laboratory Cell Differentiation and Regulation, Henan Normal University, Xinxiang 453007, China.
Int J Mol Sci. 2023 Nov 16;24(22):16410. doi: 10.3390/ijms242216410.
Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by myofibroblast abnormal activation and extracellular matrix deposition. However, the pathogenesis of PF remains unclear, and treatment options are limited. Epidemiological studies have shown that the average age of PF patients is estimated to be over 65 years, and the incidence of the disease increases with age. Therefore, PF is considered an age-related disease. A preliminary study on PF patients demonstrated that the combination therapy of the anti-senescence drugs dasatinib and quercetin improved physical functional indicators. Given the global aging population and the role of cellular senescence in tissue and organ aging, understanding the impact of cellular senescence on PF is of growing interest. This article systematically summarizes the causes and signaling pathways of cellular senescence in PF. It also objectively analyzes the impact of senescence in AECs and fibroblasts on PF development. Furthermore, potential intervention methods targeting cellular senescence in PF treatment are discussed. This review not only provides a strong theoretical foundation for understanding and manipulating cellular senescence, developing new therapies to improve age-related diseases, and extending a healthy lifespan but also offers hope for reversing the toxicity caused by the massive accumulation of senescence cells in humans.
肺纤维化(PF)是一种以肌成纤维细胞异常激活和细胞外基质沉积为特征的慢性间质性肺疾病。然而,PF 的发病机制仍不清楚,治疗选择有限。流行病学研究表明,PF 患者的平均年龄估计在 65 岁以上,且发病率随年龄增长而增加。因此,PF 被认为是一种与年龄相关的疾病。一项针对 PF 患者的初步研究表明,抗衰老药物达沙替尼和槲皮素的联合治疗改善了患者的身体功能指标。鉴于全球人口老龄化以及细胞衰老在组织和器官老化中的作用,了解细胞衰老对 PF 的影响越来越受到关注。本文系统总结了 PF 中细胞衰老的原因和信号通路。还客观分析了 AEC 和成纤维细胞衰老对 PF 发展的影响。此外,还讨论了针对 PF 治疗中细胞衰老的潜在干预方法。这篇综述不仅为理解和操纵细胞衰老、开发改善与年龄相关疾病的新疗法以及延长健康寿命提供了强有力的理论基础,也为逆转衰老细胞在人体内大量堆积所造成的毒性带来了希望。