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.

摘要： 我们的项目集中在衰老过程中骨质量的调节，我们假设这是 由骨细胞控制。我们的研究旨在确定“完整的” 衰老和衰老骨骼中的躯体机能障碍，并确定所涉及的细胞机制。 细胞和分子分析旨在将骨细胞连接、线粒体功能 和代谢对骨组织组成的影响。这些研究利用了一种独特的老鼠 年龄诱导的躯体停搏模型，基于使用他莫昔芬诱导（i） 普遍表达的Cre与GHR floxed基因（iGHRKO）结合， 验证模型（PMID：27732088）。迄今为止完成的研究表明， iGHRKO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 要求提供一份行政补充材料，用于补充研究，作为《公约》所有目标的一部分。 家长补助总体目标是测试已知的干预措施如何改变GH/IGF轴 并对寿命有有益的影响，会影响骨骼的老化。