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衰老和 SASP:多种治疗途径。

Senescence and the SASP: many therapeutic avenues.

机构信息

MRC London Institute of Medical Sciences (LMS), London W12 0NN, United Kingdom.

Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.

出版信息

Genes Dev. 2020 Dec 1;34(23-24):1565-1576. doi: 10.1101/gad.343129.120.

Abstract

Cellular senescence is a stress response that elicits a permanent cell cycle arrest and triggers profound phenotypic changes such as the production of a bioactive secretome, referred to as the senescence-associated secretory phenotype (SASP). Acute senescence induction protects against cancer and limits fibrosis, but lingering senescent cells drive age-related disorders. Thus, targeting senescent cells to delay aging and limit dysfunction, known as "senotherapy," is gaining momentum. While drugs that selectively kill senescent cells, termed "senolytics" are a major focus, SASP-centered approaches are emerging as alternatives to target senescence-associated diseases. Here, we summarize the regulation and functions of the SASP and highlight the therapeutic potential of SASP modulation as complimentary or an alternative to current senolytic approaches.

摘要

细胞衰老(Cellular senescence)是一种应激反应,会引发细胞周期的永久停滞,并引发深刻的表型变化,例如产生生物活性分泌组,称为衰老相关分泌表型(SASP)。急性衰老诱导可预防癌症并限制纤维化,但持续存在的衰老细胞会导致与年龄相关的疾病。因此,靶向衰老细胞以延缓衰老和限制功能障碍,即“衰老治疗(senotherapy)”,正在兴起。虽然选择性杀死衰老细胞的药物,称为“衰老细胞清除剂(senolytics)”是主要关注点,但以 SASP 为中心的方法作为靶向衰老相关疾病的替代方法正在出现。在这里,我们总结了 SASP 的调控和功能,并强调了 SASP 调节作为现有衰老细胞清除剂方法的补充或替代的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f2e/7706700/3dd9f4bd84ea/1565f01.jpg

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