Division of Endocrinology and Metabolism and Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota 55905.
J Clin Endocrinol Metab. 2018 Apr 1;103(4):1282-1290. doi: 10.1210/jc.2017-02694.
With the aging of the population and projected increase in osteoporotic fractures coupled with the declining use of osteoporosis medications, there is a compelling need for new approaches to treat osteoporosis. Given that age-related osteoporosis generally coexists with multiple other comorbidities (e.g., atherosclerosis, diabetes, frailty) that share aging as the leading risk factor, there is growing interest in the "Geroscience Hypothesis," which posits that manipulation of fundamental aging mechanisms will delay the appearance or severity of multiple chronic diseases because these diseases share aging as the underlying risk factor. In this context, one fundamental aging mechanism that has received considerable attention recently as contributing to multiple age-related morbidities is cellular senescence. This mini-review provides an overview on cellular senescence with a focus on its role in mediating age-related bone loss.
This summary is based on the authors' knowledge of the field supplemented by a PubMed search using the terms "senescence," "aging," and "bone."
There is compelling evidence from preclinical models and supportive human data demonstrating an increase in senescent cells in the bone microenvironment with aging. These cells produce a proinflammatory secretome that leads to increased bone resorption and decreased bone formation, and approaches that either eliminate senescent cells or impair the production of their proinflammatory secretome have been shown to prevent age-related bone loss in mice.
Targeting cellular senescence represents a novel therapeutic strategy to prevent not only bone loss but potentially multiple age-related diseases simultaneously.
随着人口老龄化以及预计骨质疏松性骨折的增加，再加上骨质疏松症药物的使用不断减少，因此迫切需要新的方法来治疗骨质疏松症。鉴于与年龄相关的骨质疏松症通常与多种其他合并症（例如动脉粥样硬化、糖尿病、虚弱）共存，这些合并症都以衰老为主要危险因素，因此人们对“衰老科学假说”越来越感兴趣，该假说假设操纵基本的衰老机制将延缓多种慢性疾病的出现或严重程度，因为这些疾病都以衰老为潜在的危险因素。在这种情况下，最近作为导致多种与年龄相关的疾病的一个基本衰老机制，细胞衰老受到了相当多的关注。这篇小型综述概述了细胞衰老，并重点介绍了其在介导与年龄相关的骨丢失中的作用。
本综述是基于作者对该领域的了解，并辅以使用“衰老”、“老化”和“骨骼”等术语在 PubMed 上进行的搜索。
有大量来自临床前模型和支持性人类数据的证据表明，随着年龄的增长，骨微环境中的衰老细胞增加。这些细胞产生促炎的分泌组，导致骨吸收增加和骨形成减少，并且已经证明消除衰老细胞或损害其促炎分泌组的产生的方法可预防小鼠的与年龄相关的骨丢失。
靶向细胞衰老代表了一种预防不仅是骨丢失而且潜在的多种与年龄相关的疾病的新的治疗策略。
