Basic Biology of Skeletal Aging: Role of Stress Response Pathways
Basic Biology of Skeletal Aging: Role of Stress Response Pathways
复制标题
DOI：
10.1093/gerona/glt079
复制
发表时间：
2013-10-01
影响因子：
5.1
通讯作者：
OBrien, Charles A.
中科院分区：
文献类型：
--
作者：
Almeida, Maria;OBrien, Charles A.
尽管骨形成下降和骨量丢失是人类衰老的常见特征，但介导这些效应的分子机制仍不清楚。来自小鼠药理学和遗传学研究的证据为骨中氧化应激的有害作用提供了支持，并加强了以下观点：随着年龄的增长，活性氧（ROS）的增加代表了年龄相关性骨丢失的病理生理机制。间充质干细胞和骨细胞是长寿细胞，因此比其他类型的骨细胞更容易受到衰老引起的分子变化的影响，包括ROS水平增加和自噬减少。然而，短寿命的细胞，如成骨细胞祖细胞和成熟的成骨细胞和破骨细胞也受到改变的老化环境的影响，其特征在于较低水平的性类固醇，增加的内源性糖皮质激素和较高的氧化脂质。本文综述了目前的知识对骨的老化过程中的影响，特别强调在小鼠成骨细胞谱系细胞中的ROS和自噬的作用。
Although a decline in bone formation and loss of bone mass are common features of human aging, the molecular mechanisms mediating these effects have remained unclear. Evidence from pharmacological and genetic studies in mice has provided support for a deleterious effect of oxidative stress in bone and has strengthened the idea that an increase in reactive oxygen species (ROS) with advancing age represents a pathophysiological mechanism underlying age-related bone loss. Mesenchymal stem cells and osteocytes are long-lived cells and, therefore, are more susceptible than other types of bone cells to the molecular changes caused by aging, including increased levels of ROS and decreased autophagy. However, short-lived cells like osteoblast progenitors and mature osteoblasts and osteoclasts are also affected by the altered aged environment characterized by lower levels of sex steroids, increased endogenous glucocorticoids, and higher oxidized lipids. This article reviews current knowledge on the effects of the aging process on bone, with particular emphasis on the role of ROS and autophagy in cells of the osteoblast lineage in mice.