Fu Yichu, Wang Binhan, Alu Aqu, Hong Weiqi, Lei Hong, He Xuemei, Shi Huashan, Cheng Ping, Yang Xiangliang
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Signal Transduct Target Ther. 2025 Aug 6;10(1):250. doi: 10.1038/s41392-025-02371-z.
Immunosenescence refers to the abnormal activation or dysfunction of the immune system as people age. Inflammaging is a typical pathological inflammatory state associated with immunosenescence and is characterized by excessive expression of proinflammatory cytokines in aged immune cells. Chronic inflammation contributes to a variety of age-related diseases, such as neurodegenerative disease, cancer, infectious disease, and autoimmune diseases. Although not fully understood, recent studies contribute greatly to uncovering the underlying mechanisms of immunosenescence at the molecular and cellular levels. Immunosenescence is associated with dysregulated signaling pathways (e.g., overactivation of the NF-κB signaling pathway and downregulation of the melatonin signaling pathway) and abnormal immune cell responses with functional alterations and phenotypic shifts. These advances remarkably promote the development of countermeasures against immunosenescence for the treatment of age-related diseases. Some anti-immunosenescence treatments have already shown promising results in clinical trials. In this review, we discuss the molecular and cellular mechanisms of immunosenescence and summarize the critical role of immunosenescence in the pathogenesis of age-related diseases. Potential interventions to mitigate immunosenescence, including reshaping immune organs, targeting different immune cells or signaling pathways, and nutritional and lifestyle interventions, are summarized. Some treatment strategies have already launched into clinical trials. This study aims to provide a systematic and comprehensive introduction to the basic and clinical research progress of immunosenescence, thus accelerating research on immunosenescence in related diseases and promoting the development of targeted therapy.
免疫衰老指的是随着人们年龄增长，免疫系统出现异常激活或功能障碍。炎症衰老 是一种与免疫衰老相关的典型病理性炎症状态，其特征是老年免疫细胞中促炎细胞因子过度表达。慢性炎症会导致多种与年龄相关的疾病，如神经退行性疾病、癌症、传染病和自身免疫性疾病。尽管尚未完全了解，但最近的研究在揭示免疫衰老在分子和细胞水平上的潜在机制方面做出了巨大贡献。免疫衰老与信号通路失调（例如，NF-κB信号通路过度激活和褪黑素信号通路下调）以及具有功能改变和表型转变的异常免疫细胞反应有关。这些进展显著促进了针对免疫衰老的对策的发展，以治疗与年龄相关的疾病。一些抗免疫衰老治疗在临床试验中已经显示出有希望的结果。在这篇综述中，我们讨论了免疫衰老的分子和细胞机制，并总结了免疫衰老在与年龄相关疾病发病机制中的关键作用。总结了减轻免疫衰老的潜在干预措施，包括重塑免疫器官、靶向不同免疫细胞或信号通路以及营养和生活方式干预。一些治疗策略已经进入临床试验。本研究旨在对免疫衰老的基础和临床研究进展进行系统全面的介绍，从而加速相关疾病中免疫衰老的研究，促进靶向治疗的发展。
