Division of Endocrinology, Mayo Clinic, Rochester, MN, USA.
Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
Nat Rev Endocrinol. 2020 May;16(5):263-275. doi: 10.1038/s41574-020-0335-y. Epub 2020 Mar 11.
With the ageing of the global population, interest is growing in the 'geroscience hypothesis', which posits that manipulation of fundamental ageing mechanisms will delay (in parallel) the appearance or severity of multiple chronic, non-communicable diseases, as these diseases share the same underlying risk factor - namely, ageing. In this context, cellular senescence has received considerable attention as a potential target in preventing or treating multiple age-related diseases and increasing healthspan. Here we review mechanisms of cellular senescence and approaches to target this pathway therapeutically using 'senolytic' drugs that kill senescent cells or inhibitors of the senescence-associated secretory phenotype (SASP). Furthermore, we highlight the evidence that cellular senescence has a causative role in multiple diseases associated with ageing. Finally, we focus on the role of cellular senescence in a number of endocrine diseases, including osteoporosis, metabolic syndrome and type 2 diabetes mellitus, as well as other endocrine conditions. Although much remains to be done, considerable preclinical evidence is now leading to the initiation of proof-of-concept clinical trials using senolytics for several endocrine and non-endocrine diseases.
随着全球人口老龄化，人们对“衰老科学假说”越来越感兴趣，该假说认为，操纵基本衰老机制将（平行地）延缓多种慢性非传染性疾病的出现或严重程度，因为这些疾病具有相同的潜在风险因素——即衰老。在这种情况下，细胞衰老作为预防或治疗多种与年龄相关疾病和增加健康寿命的潜在靶点受到了相当大的关注。在这里，我们回顾了细胞衰老的机制，并讨论了使用“衰老细胞清除剂”药物靶向该途径的方法，这些药物可以杀死衰老细胞或抑制衰老相关分泌表型 (SASP)。此外，我们强调了细胞衰老在与衰老相关的多种疾病中起因果作用的证据。最后，我们关注细胞衰老在许多内分泌疾病中的作用，包括骨质疏松症、代谢综合征和 2 型糖尿病，以及其他内分泌疾病。尽管还有很多工作要做，但大量的临床前证据正促使人们开始使用衰老细胞清除剂治疗几种内分泌和非内分泌疾病的概念验证临床试验。
