Diverse effects of somatopause and aging on the skeleton

躯体更年期和衰老对骨骼的多种影响

• 批准号: 10409076
• 负责人: MITCHELL B SCHAFFLER
• 金额: $ 15.85万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10409076
• 关键词: Administrative Supplement; Affect; Age; Aging; Bone Tissue; Cell Death; Cessation of life; Energy Metabolism; Funding; Genes; Goals; Homeostasis; Impairment; Insulin-Like Growth Factor I; Intervention; Link; Longevity; LoxP-flanked allele; Metabolic; Metabolism; Mitochondria; Modeling; Molecular Analysis; Morphology; Nutrient; Osteocytes; Oxidation-Reduction; Production; Reactive Oxygen Species; Signal Transduction; Skeleton; Tamoxifen; Testing; age related; base; bone; bone quality; design; flexibility; mouse model; parent grant; response; sensor

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.

抽象的： 我们的项目着重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`完整之间的相互作用 衰老骨骼中的衰老和体积，并确定所涉及的细胞机制。 细胞和分子分析旨在连接骨细胞连接性，线粒体功能 和骨组织组成的代谢。这些研究资本使用独特的鼠标 年龄诱导的体系模型，该模型基于使用他莫昔芬诱导（i）的使用 与GHR Floxed Gene（Ighrko）结合使用的普遍表达的CRE，以前 经过验证的模型（PMID：27732088）。到目前为止完成的研究表明 IGHRKO会损害骨形态，骨组织质量，骨细胞连接性和骨细胞 线粒体功能。 作为所有目标的一部分，要求进行行政补充进行互补研究 父母赠款。总体目标是测试已知如何修改GH/IGF轴的干预措施 并对寿命具有有益作用会影响衰老的骨骼。