Nature Medicine ( IF 82.9 ) Pub Date : 2022-08-11 , DOI: 10.1038/s41591-022-01923-y Selim Chaib 1 , Tamar Tchkonia 1 , James L Kirkland 1, 2
Interlinked and fundamental aging processes appear to be a root-cause contributor to many disorders and diseases. One such process is cellular senescence, which entails a state of cell cycle arrest in response to damaging stimuli. Senescent cells can arise throughout the lifespan and, if persistent, can have deleterious effects on tissue function due to the many proteins they secrete. In preclinical models, interventions targeting those senescent cells that are persistent and cause tissue damage have been shown to delay, prevent or alleviate multiple disorders. In line with this, the discovery of small-molecule senolytic drugs that selectively clear senescent cells has led to promising strategies for preventing or treating multiple diseases and age-related conditions in humans. In this Review, we outline the rationale for senescent cells as a therapeutic target for disorders across the lifespan and discuss the most promising strategies—including recent and ongoing clinical trials—for translating small-molecule senolytics and other senescence-targeting interventions into clinical use.
中文翻译:
细胞衰老和senolytics:通往临床的道路
相互关联且基本的衰老过程似乎是许多疾病和疾病的根本原因。一个这样的过程是细胞衰老,它需要细胞周期停滞状态以响应破坏性刺激。衰老细胞可以在整个生命周期中出现,如果持续存在,由于它们分泌的许多蛋白质会对组织功能产生有害影响。在临床前模型中,针对那些持续存在并导致组织损伤的衰老细胞的干预措施已被证明可以延迟、预防或缓解多种疾病。与此一致,选择性清除衰老细胞的小分子抗衰老药物的发现为预防或治疗人类多种疾病和与年龄相关的疾病带来了有希望的策略。在这篇评论中,