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The role of cellular senescence in ageing and endocrine disease.
Nature Reviews Endocrinology ( IF 31.0 ) Pub Date : 2020-03-11 , DOI: 10.1038/s41574-020-0335-y Sundeep Khosla 1, 2 , Joshua N Farr 1, 2 , Tamara Tchkonia 1, 2 , James L Kirkland 1, 2
Nature Reviews Endocrinology ( IF 31.0 ) Pub Date : 2020-03-11 , DOI: 10.1038/s41574-020-0335-y Sundeep Khosla 1, 2 , Joshua N Farr 1, 2 , Tamara Tchkonia 1, 2 , James L Kirkland 1, 2
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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.
中文翻译：
细胞衰老在衰老和内分泌疾病中的作用。
随着全球人口的老龄化，人们对“老年科学假说”的兴趣日益浓厚，该假说认为，操纵基本的衰老机制将延迟（同时）多种慢性非传染性疾病的出现或严重程度，因为这些疾病具有共同的特征同样的潜在风险因素——即衰老。在这种背景下，细胞衰老作为预防或治疗多种与年龄相关的疾病和延长健康寿命的潜在目标受到了相当多的关注。在这里，我们回顾了细胞衰老的机制以及使用杀死衰老细胞的“衰老”药物或衰老相关分泌表型（SASP）抑制剂来靶向该途径的治疗方法。此外，我们强调了细胞衰老在多种与衰老相关的疾病中起致病作用的证据。最后，我们重点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现在正在启动使用 senolytics 治疗多种内分泌和非内分泌疾病的概念验证临床试验。
更新日期：2020-03-11
中文翻译：
细胞衰老在衰老和内分泌疾病中的作用。
随着全球人口的老龄化，人们对“老年科学假说”的兴趣日益浓厚，该假说认为，操纵基本的衰老机制将延迟（同时）多种慢性非传染性疾病的出现或严重程度，因为这些疾病具有共同的特征同样的潜在风险因素——即衰老。在这种背景下，细胞衰老作为预防或治疗多种与年龄相关的疾病和延长健康寿命的潜在目标受到了相当多的关注。在这里，我们回顾了细胞衰老的机制以及使用杀死衰老细胞的“衰老”药物或衰老相关分泌表型（SASP）抑制剂来靶向该途径的治疗方法。此外，我们强调了细胞衰老在多种与衰老相关的疾病中起致病作用的证据。最后，我们重点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现在正在启动使用 senolytics 治疗多种内分泌和非内分泌疾病的概念验证临床试验。
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