Chen Jia, Li Hongyu, Huang Yongyin, Tang Qiang
Heilongjiang University of Chinese Medicine, Harbin, China.
Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.
Front Aging. 2024 Oct 23;5:1486281. doi: 10.3389/fragi.2024.1486281. eCollection 2024.
Aging is a universal physiological phenomenon, and chronic age-related diseases have become one of the leading causes of human mortality, accounting for nearly half of all deaths. Studies have shown that reducing the incidence of these diseases can not only extend lifespan but also promote healthy aging. In recent years, the potential role of non-histone high-mobility group proteins (HMGs) in the regulation of aging and lifespan has attracted widespread attention. HMGs play critical roles in cellular senescence and associated diseases through various pathways, encompassing multi-layered mechanisms involving protein interactions, molecular regulation, and chromatin dynamics. This review provides a comprehensive analysis of the interactions between HMG family proteins and senescence-associated secretory phenotype (SASP), chromatin structure, and histone modifications, offering a deeper exploration of the pivotal functions and impacts of HMGs in the aging process. Furthermore, we summarize recent findings on the contributions of HMG proteins to aging and age-related diseases. HMG proteins not only regulate senescence-associated inflammation through modulating the SASP but also influence genomic stability and cell fate decisions via interactions with chromatin and histones. Targeting HMG proteins holds great potential in delaying the progression of aging and its associated diseases. This review aims to provide a systematic overview of HMG proteins' roles in aging and to lay a solid foundation for future anti-aging drug development and therapeutic strategies. With the advancing understanding of the mechanisms by which HMGs regulate aging, developing therapeutic interventions targeting HMGs may emerge as a promising approach to extending lifespan and enhancing healthspan.
衰老 是一种普遍的生理现象，与年龄相关的慢性疾病已成为人类死亡的主要原因之一，占所有死亡人数的近一半。研究表明，降低这些疾病的发病率不仅可以延长寿命，还能促进健康衰老。近年来，非组蛋白高迁移率族蛋白（HMGs）在衰老和寿命调节中的潜在作用引起了广泛关注。HMGs 通过多种途径在细胞衰老及相关疾病中发挥关键作用，涉及蛋白质相互作用、分子调控和染色质动态变化等多层次机制。本综述全面分析了 HMG 家族蛋白与衰老相关分泌表型（SASP）、染色质结构和组蛋白修饰之间的相互作用，深入探讨了 HMGs 在衰老过程中的关键功能和影响。此外，我们总结了 HMG 蛋白对衰老和年龄相关疾病影响的最新研究结果。HMG 蛋白不仅通过调节 SASP 来调控衰老相关炎症，还通过与染色质和组蛋白的相互作用影响基因组稳定性和细胞命运决定。靶向 HMG 蛋白在延缓衰老及其相关疾病进展方面具有巨大潜力。本综述旨在系统概述 HMG 蛋白在衰老中的作用，为未来抗衰老药物开发和治疗策略奠定坚实基础。随着对 HMGs 调节衰老机制认识的不断深入，开发靶向 HMGs 的治疗干预措施可能成为延长寿命和提高健康寿命的一种有前景的方法。
