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热休克蛋白 90 抑制剂作为衰老细胞清除剂以延长健康衰老。

Hsp90 inhibitors as senolytic drugs to extend healthy aging.

机构信息

a Department of Molecular Medicine and The Center on Aging , The Scripps Research Institute , Jupiter , FL , USA.

出版信息

Cell Cycle. 2018;17(9):1048-1055. doi: 10.1080/15384101.2018.1475828. Epub 2018 Jul 23.

Abstract

Aging is characterized by progressive decay of biological systems and although it is not considered a disease, it is one of the main risk factors for chronic diseases and many types of cancers. The accumulation of senescent cells in various tissues is thought to be a major factor contributing to aging and age-related diseases. Removal of senescent cells during aging by either genetic or therapeutic methods have led to an improvement of several age related disease in mice. In this preview, we highlight the significance of developing senotherapeutic approaches to specifically kill senescent cells (senolytics) or suppress the senescence-associated secretory phenotype (SASP) that drives sterile inflammation (senomorphics) associated with aging to extend healthspan and potentially lifespan. Also, we provide an overview of the senotherapeutic drugs identified to date. In particular, we discuss and expand upon the recent identification of inhibitors of the HSP90 co-chaperone as a new class of senolytics.

摘要

衰老是生物系统进行性衰退的特征,尽管它不被认为是一种疾病,但它是慢性疾病和许多类型癌症的主要危险因素之一。各种组织中衰老细胞的积累被认为是导致衰老和与年龄相关疾病的主要因素之一。通过遗传或治疗方法在衰老过程中去除衰老细胞,导致小鼠的几种与年龄相关的疾病得到改善。在这篇预览中,我们强调了开发专门杀死衰老细胞的治疗方法(衰老细胞清除剂)或抑制驱动与衰老相关的无菌性炎症(衰老模拟物)的衰老相关分泌表型(SASP)的重要性,以延长健康寿命并可能延长寿命。此外,我们还概述了迄今为止确定的衰老治疗药物。特别是,我们讨论并扩展了最近发现的 HSP90 共伴侣抑制剂作为一种新的衰老细胞清除剂。

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