Nakano Yasuhiro, Johmura Yoshikazu
Division of Cancer and Senescence Biology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192 Japan.
Integrated Systems of Aging Research Unit, Institute for Frontier Science Initiative, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192 Japan.
J Biochem. 2025 Mar 4;177(3):189-195. doi: 10.1093/jb/mvae098.
As the global population continues to age, understanding the complex role of cellular senescence and its implications in healthy lifespans has gained increasing prominence. Cellular senescence is defined as the irreversible cessation of cell proliferation, accompanied by the secretion of a range of pro-inflammatory factors, collectively termed the senescence-associated secretory phenotype (SASP), in response to various cellular stresses. While the accumulation of senescent cells has been strongly implicated in the ageing process and the pathogenesis of age-related diseases owing to their pro-inflammatory properties, recent research has also highlighted their essential roles in processes such as tumour suppression, tissue development and repair. This review provides a comprehensive examination of the dual nature of senescent cells, evaluating their deleterious contributions to chronic inflammation, tissue dysfunction and disease, as well as their beneficial roles in maintaining physiological homeostasis. Additionally, we explored the therapeutic potential of senolytic agents designed to selectively eliminate detrimental senescent cells while considering the delicate balance between transient and beneficial senescence and the persistence of pathological senescence. A deeper understanding of these dynamics is critical to develop novel interventions aimed at mitigating age-related dysfunctions and enhancing healthy life expectancies.
随着全球人口持续老龄化，了解细胞衰老的复杂作用及其对健康寿命的影响变得越来越重要。细胞衰老被定义为细胞增殖的不可逆停止，伴随着一系列促炎因子的分泌，这些因子统称为衰老相关分泌表型（SASP），以应对各种细胞应激。虽然衰老细胞的积累因其促炎特性而与衰老过程和年龄相关疾病的发病机制密切相关，但最近的研究也强调了它们在肿瘤抑制、组织发育和修复等过程中的重要作用。本综述全面审视了衰老细胞的双重性质，评估了它们对慢性炎症、组织功能障碍和疾病的有害影响，以及它们在维持生理稳态中的有益作用。此外，我们探讨了溶衰老剂的治疗潜力，旨在选择性地消除有害的衰老细胞，同时考虑短暂性和有益性衰老之间的微妙平衡以及病理性衰老的持续性。深入了解这些动态对于开发旨在减轻与年龄相关的功能障碍和延长健康预期寿命的新型干预措施至关重要。
