Insights into targeting cellular senescence with senolytic therapy: The journey from preclinical trials to clinical practice

IF 5.3 3区 医学 Q2 CELL BIOLOGY Mechanisms of Ageing and Development Pub Date : 2024-02-23 DOI:10.1016/j.mad.2024.111918
Peng Chen , Yulai Wang , Benhong Zhou
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Abstract

Interconnected, fundamental aging processes are central to many illnesses and diseases. Cellular senescence is a mechanism that halts the cell cycle in response to harmful stimuli. Senescent cells (SnCs) can emerge at any point in life, and their persistence, along with the numerous proteins they secrete, can negatively affect tissue function. Interventions aimed at combating persistent SnCs, which can destroy tissues, have been used in preclinical models to delay, halt, or even reverse various diseases. Consequently, the development of small-molecule senolytic medicines designed to specifically eliminate SnCs has opened potential avenues for the prevention or treatment of multiple diseases and age-related issues in humans. In this review, we explore the most promising approaches for translating small-molecule senolytics and other interventions targeting senescence in clinical practice. This discussion highlights the rationale for considering SnCs as therapeutic targets for diseases affecting individuals of all ages.

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以细胞衰老为靶点的衰老疗法:从临床前试验到临床实践的历程。
相互关联的基本衰老过程是许多疾病的核心。细胞衰老是一种在有害刺激下停止细胞周期的机制。衰老细胞(SnCs)可在生命的任何阶段出现,它们的持续存在及其分泌的大量蛋白质会对组织功能产生负面影响。衰老细胞会破坏组织,旨在对抗衰老细胞的干预措施已被用于临床前模型,以延缓、阻止甚至逆转各种疾病。因此,专为消除 SnCs 而设计的小分子衰老分解药物的开发为预防或治疗人类多种疾病和与年龄相关的问题开辟了潜在的途径。在这篇综述中,我们探讨了将小分子衰老溶解剂和其他针对衰老的干预措施转化为临床实践的最有前景的方法。这一讨论强调了将SnCs作为影响所有年龄段人群的疾病治疗靶点的合理性。
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来源期刊
CiteScore
11.10
自引率
1.90%
发文量
79
审稿时长
32 days
期刊介绍: Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms. Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.
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