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肺衰老在慢性呼吸系统疾病中的研究进展

周凯¹, 陈龙², 秦晓群¹, 向阳¹, 瞿湘萍¹, 刘惠君¹, 刘持^1,*

¹中南大学基础医学院生理学系，长沙 410078；²新疆医科大学基础医学院机能实验中心，乌鲁木齐 830017

摘要

细胞衰老是一个极其复杂的过程，其特征表现为线粒体结构功能障碍、端粒缩短、炎症微环境、蛋白稳态失衡、表观遗传改变、DNA损伤修复异常等，进而导致组织和器官的结构、功能损伤并诱发衰老相关疾病的发生和发展。衰老既包括增龄引起的生理性衰老，还包括多种因素所诱发的病理性衰老。值得注意的是，肺作为与外界空气直接接触的靶器官更易于遭受多种刺激而出现病理性早衰，即肺衰老。研究发现在大多数慢性呼吸系统疾病的肺内都存在一定比例的衰老细胞，但是这些衰老细胞诱导肺衰老及其在慢性呼吸系统疾病中作用的内在机制仍很不清楚。本文重点描述了肺衰老的诱因和分类、肺衰老参与慢性呼吸系统疾病的内在机制及抗衰老治疗在慢性呼吸系统疾病中的应用，有望为临床上慢性呼吸系统疾病的防治提供新的研究思路和理论依据。

关键词： 细胞衰老; 慢性呼吸系统疾病; 衰老相关分泌表型; Senolytic药物; CAR-T细胞疗法

Research progress of lung aging in chronic respiratory diseases

ZHOU Kai¹, CHEN Long², QIN Xiao-Qun¹, XIANG Yang¹, QU Xiang-Ping¹, LIU Hui-Jun¹, LIU Chi^1,*

¹Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410078, China；²Functional Experiment Center, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830017, China

Abstract

Cell aging is an extremely complex process, which is characterized by mitochondrial structural dysfunction, telomere shortening, inflammatory microenvironment, protein homeostasis imbalance, epigenetic changes, abnormal DNA damage and repair, etc. Aging is usually accompanied by structural and functional damage of tissues and organs which further induces the occurrence and development of aging-related diseases. Aging includes physiological aging caused by increased age and pathological aging induced by a variety of factors. Noteworthy, as a target organ directly contacting with the outside air, lung is more prone to various stimuli, causing pathological premature aging which is lung aging. Studies have found that there is a certain proportion of senescent cells in the lungs of most chronic respiratory diseases. However, the underlying mechanism by which these senescent cells induce lung senescence and their role in chronic respiratory diseases is still obscure. This paper focuses on the causes and classification of lung aging, the internal mechanism of lung aging involved in chronic respiratory diseases, and the application of anti-aging treatments in chronic respiratory diseases. We hope to provide new research ideas and theoretical basis for the clinical prevention and treatment in chronic respiratory diseases.

Key words: cell senescence; chronic respiratory disease; senescence-associated secretory phenotype (SASP); Senolytic drugs; chimeric antigen receptor (CAR)-T cell therapy

收稿日期：　　录用日期：

通讯作者：刘持　　E-mail: liu.chi@csu.edu.cn

DOI: 10.13294/j.aps.2022.0036

引用本文：

周凯, 陈龙, 秦晓群, 向阳, 瞿湘萍, 刘惠君, 刘持. 肺衰老在慢性呼吸系统疾病中的研究进展[J]. 生理学报 2022; 74 (3): 479-488.

ZHOU Kai, CHEN Long, QIN Xiao-Qun, XIANG Yang, QU Xiang-Ping, LIU Hui-Jun, LIU Chi. Research progress of lung aging in chronic respiratory diseases. Acta Physiol Sin 2022; 74 (3): 479-488 (in Chinese with English abstract).