Chen Xing-Yi, Wang Dong-Mei, Zhou Ya, Liu Li, Zhu Tao, Ran Zhao, Lu Mei-Hong, Mu Ben-Rong
Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu, 611137, Sichuan, China.
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Mol Biol Rep. 2025 Jun 7;52(1):565. doi: 10.1007/s11033-025-10665-2.
Pulmonary fibrosis is often associated with aging, marked notably by the senescence of lung epithelial cells and the development of interstitial fibrosis. Mitophagy plays a crucial role in aging by degrading damaged mitochondria, thereby maintaining mitochondrial quality and cellular homeostasis. When mitophagy is disrupted or impaired, damaged mitochondria fail to be properly degraded by lysosomes. This results in the persistence of dysfunctional mitochondria, which can further damage cells, induce cell senescence and trigger inflammatory responses. These processes can worsen pulmonary fibrosis. Restoring proper mitophagy could be a promising strategy for managing pulmonary fibrosis and countering stress-induced premature cell senescence, potentially improving or even reversing lung function in aging lungs. This review will explore the complex relationship between cell senescence and pulmonary fibrosis, detailing the senescence characteristics in fibrotic lungs. It will also highlight recent advancements in understanding how mitophagy influences lung senescence and fibrosis and discuss potential therapeutic strategies to address mitophagy dysfunction in treating pulmonary fibrosis.
肺纤维化常与衰老相关，显著特征为肺上皮细胞衰老和间质纤维化的发展。线粒体自噬通过降解受损线粒体在衰老过程中发挥关键作用，从而维持线粒体质量和细胞稳态。当线粒体自噬被破坏或受损时，受损线粒体无法被溶酶体正常降解。这导致功能失调的线粒体持续存在，进而可进一步损伤细胞、诱导细胞衰老并引发炎症反应。这些过程会使肺纤维化恶化。恢复适当的线粒体自噬可能是控制肺纤维化和对抗应激诱导的细胞早衰的一种有前景的策略，有可能改善甚至逆转衰老肺脏的肺功能。本综述将探讨细胞衰老与肺纤维化之间的复杂关系，详细阐述纤维化肺脏中的衰老特征。还将重点介绍在理解线粒体自噬如何影响肺衰老和纤维化方面的最新进展，并讨论在治疗肺纤维化中解决线粒体自噬功能障碍的潜在治疗策略。
