Wissler Gerdes Erin O, Zhu Yi, Tchkonia Tamar, Kirkland James L
Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
FEBS J. 2020 Jun;287(12):2418-2427. doi: 10.1111/febs.15264. Epub 2020 Mar 17.
Senescent cells accumulate with aging and at etiological sites of multiple diseases, including those accounting for most morbidity, mortality, and health costs. Senescent cells do not replicate, can release factors that cause tissue dysfunction, and yet remain viable. The discovery of senolytic drugs, agents that selectively eliminate senescent cells, created a new route for alleviating age-related dysfunction and diseases. As anticipated for agents targeting fundamental aging mechanisms that are 'root cause' contributors to multiple disorders, potential applications of senolytics are protean. We review the discovery of senolytics, strategies for translation into clinical application, and promising early signals from clinical trials.
衰老细胞随着年龄增长以及在多种疾病的病因部位积累，这些疾病包括导致大多数发病、死亡和医疗成本的疾病。衰老细胞不再复制，可释放导致组织功能障碍的因子，但仍保持存活。衰老细胞裂解药物（即选择性清除衰老细胞的药物）的发现，为缓解与年龄相关的功能障碍和疾病开辟了一条新途径。正如预期的那样，针对作为多种疾病“根本原因”的基本衰老机制的药物，衰老细胞裂解药物的潜在应用十分广泛。我们综述了衰老细胞裂解药物的发现、转化为临床应用的策略以及来自临床试验的有前景的早期信号。
