Diverse effects of somatopause and aging on the skeleton

摘要： 我们的项目专注于衰老过程中骨骼质量的调节，我们假设这是 由骨细胞控制。我们的研究旨在确定完整的 研究衰老骨骼中的衰老和躯体更年期，并确定相关的细胞机制。 细胞和分子分析的目的是将骨细胞连接、线粒体功能 代谢对骨组织成分的影响。这些研究利用了一种独特的鼠标 基于三苯氧胺诱导剂的年龄诱导性更年期模型(I) 与GHR FLOXED基因(IGHRKO)一起普遍表达的Cre，以前 经过验证的模型(PMID：27732088)。到目前为止已经完成的研究表明，躯体更年期在 IGHRKO损害骨形态、骨组织质量、骨细胞连通性和骨细胞 线粒体功能。 要求为补充研究提供行政补充资料，作为委员会所有目标的一部分 家长助学金。总体目标是测试已知的干预措施如何改变生长激素/胰岛素样生长因子轴 并对延年益寿有好处，会影响骨骼老化。

ABSTRACT: Our project focuses on the modulation of bone quality during aging, which we hypothesize is controlled by osteocytes. Our studies are designed to determine the interactions between `intact aging' and somatopause in the aging skeleton and to identify the cellular mechanisms involved. Cellular and molecular analyses are aimed at linking osteocyte connectivity, mitochondrial function and metabolism to bone tissue composition. These studies capitalize on using a unique mouse model of age-induced somatopause, which is based on the use of tamoxifen-inducible (i) ubiquitously-expressed Cre in conjunction with the GHR floxed gene (iGHRKO), a previously validated model (PMID:27732088). Studies accomplished so far have revealed that somatopause in the iGHRKO impairs bone morphology, bone tissue quality, osteocyte connectivity, and osteocyte mitochondrial function. An administrative supplement is requested for complementary studies as part of all aims of the parent grant. The overall goal is to test how interventions that are known to modify the GH/IGF axis and have beneficial effect on lifespan will affect the aging skeleton.