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靶向细胞衰老的细胞衰老疗法的研究进展:从临床前试验到临床实践。

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

机构信息

Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China.

Department of Pharmacy, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, P.R. China.

出版信息

Mech Ageing Dev. 2024 Apr;218:111918. doi: 10.1016/j.mad.2024.111918. Epub 2024 Feb 23.

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.

摘要

相互关联的基本衰老过程是许多疾病的核心。细胞衰老是一种响应有害刺激而停止细胞周期的机制。衰老细胞 (SnC) 可以在生命中的任何时候出现,它们的持续存在以及它们分泌的许多蛋白质会对组织功能产生负面影响。旨在对抗持续存在的 SnC 的干预措施已在临床前模型中使用,以延迟、阻止甚至逆转各种疾病。因此,开发旨在专门消除 SnC 的小分子衰老药物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途径。在这篇综述中,我们探讨了将小分子衰老药物和其他针对衰老的干预措施转化为临床实践的最有前途的方法。这一讨论强调了将 SnC 作为影响所有年龄段个体的疾病的治疗靶点的合理性。

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