Lavarti Rupa, Alvarez-Diaz Tatiana, Marti Kyarangelie, Kar Parmita, Raju Raghavan Pillai
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA, United States.
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA, United States; Charlie Norwood VA Medical Center, Augusta, GA, United States.
Ageing Res Rev. 2025 Jul;109:102760. doi: 10.1016/j.arr.2025.102760. Epub 2025 May 1.
Aging is characterized by a steady loss of physiological integrity, leading to impaired function and increased vulnerability to death. Cell senescence is a biological process that progresses with aging and is believed to be a key driver of age-related diseases. Senescence, a hallmark of aging, also demonstrates its beneficial physiological aspects as an anti-cancer, pro-regenerative, homeostatic, and developmental mechanism. A transitory response in which the senescent cells are quickly formed and cleared may promote tissue regeneration and organismal fitness. At the same time, senescence-related secretory phenotypes associated with extended senescence can have devastating effects. The fact that the interaction between senescent cells and their surroundings is very context-dependent may also help to explain this seemingly opposing pleiotropic function. Further, mitochondrial dysfunction is an often-unappreciated hallmark of cellular senescence and figures prominently in multiple feedback loops that induce and maintain the senescent phenotype. This review summarizes the mechanism of cellular senescence and the significance of acute senescence. We concisely introduced the context-dependent role of senescent cells and SASP, aspects of mitochondrial biology altered in the senescent cells, and their impact on the senescent phenotype. Finally, we conclude with recent therapeutic advancements targeting cellular senescence, focusing on acute injuries and age-associated diseases. Collectively, these insights provide a future roadmap for the role of senescence in organismal fitness and life span extension.
衰老的特征是生理完整性不断丧失，导致功能受损和死亡易感性增加。细胞衰老 是一个随着衰老而进展的生物学过程，被认为是与年龄相关疾病的关键驱动因素。衰老作为衰老的一个标志，也展现出其作为抗癌、促再生、体内平衡和发育机制的有益生理方面。衰老细胞快速形成并清除的短暂反应可能促进组织再生和机体健康。与此同时，与延长衰老相关的衰老相关分泌表型可能具有毁灭性影响。衰老细胞与其周围环境之间的相互作用非常依赖于环境这一事实，也可能有助于解释这种看似相反的多效性功能。此外，线粒体功能障碍是细胞衰老一个常被忽视的标志，在诱导和维持衰老表型的多个反馈回路中起着重要作用。本综述总结了细胞衰老的机制以及急性衰老的意义。我们简要介绍了衰老细胞和衰老相关分泌表型依赖于环境的作用、衰老细胞中线粒体生物学改变的方面及其对衰老表型的影响。最后，我们总结了针对细胞衰老的最新治疗进展，重点关注急性损伤和与年龄相关的疾病。总的来说，这些见解为衰老在机体健康和寿命延长中的作用提供了未来路线图。
