The context-dependent effect of cellular senescence: From embryogenesis and wound healing to aging

IF 12.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2025-05-01 DOI:10.1016/j.arr.2025.102760

Rupa Lavarti , Tatiana Alvarez-Diaz , Kyarangelie Marti , Parmita Kar , Raghavan Pillai Raju

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引用次数: 0

Abstract

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.

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细胞衰老的环境依赖效应：从胚胎发生和伤口愈合到衰老

衰老的特征是生理完整性的不断丧失，导致功能受损和对死亡的脆弱性增加。细胞衰老是一个随着年龄增长而发展的生物学过程，被认为是年龄相关疾病的关键驱动因素。衰老是衰老的一个标志，也显示了其有益的生理方面，如抗癌、促进再生、体内平衡和发育机制。衰老细胞迅速形成和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的分泌表型可能具有破坏性的影响。衰老细胞与其周围环境之间的相互作用是非常依赖于环境的，这一事实也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的一个经常被忽视的标志，并在诱导和维持衰老表型的多个反馈回路中发挥着重要作用。本文就细胞衰老的机制及急性衰老的意义作一综述。我们简要介绍了衰老细胞和SASP的环境依赖性作用，衰老细胞中线粒体生物学的改变，以及它们对衰老表型的影响。最后，我们总结了最近针对细胞衰老的治疗进展，重点是急性损伤和年龄相关疾病。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的路线图。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.