OSTEOCYTE REGULATION OF BONE/MUSCLE WITH AGING

骨细胞对骨骼/肌肉衰老的调节

• 批准号: 10166739
• 负责人: Lynda F Bonewald
• 金额: $ 208.1万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10166739
• 关键词: Affect; Age; Aging; Attenuated; Brain; Cell Death; Cell Line; Cell Survival; Cell physiology; Cells; Contracts; Data; Dendrites; Dinoprostone; Disease; Disease Progression; Distant; Endocrine; Engineering; Estrogens; Exercise; Functional disorder; Goals; Health; Health Care Costs; Heart; Immobilization; Individual; Intervention; Kidney; Lead; Maintenance; Messenger RNA; Metabolism; MicroRNAs; Mitochondria; Molecular; Molecular Weight; Movement; Muscle; Muscle Cells; Muscle Contraction; Muscle Fibers; Muscle function; Muscular Atrophy; Musculoskeletal Diseases; Musculoskeletal System; Organ; Organism; Osteoblasts; Osteocytes; Osteoporosis; Oxidative Stress; Pathway interactions; Physiological; Play; Production; Proteins; Regulation; Resources; Role; Signal Pathway; Signal Transduction; Skeleton; Societies; Structure; System; Testing; Therapeutic; Time; Tissues; Transgenic Mice; Twin Multiple Birth; United States; age effect; aging population; beta catenin; bone; bone cell; bone loss; bone mass; cost; extracellular vesicles; heart function; imaging capabilities; innovation; interdisciplinary approach; intravital imaging; lipidomics; live cell imaging; mechanical load; metabolomics; mouse model; muscle form; myogenesis; preservation; prevent; programs; protective factors; response; sarcopenia; sedentary; success; tool

Abstract: Our society is becoming more and more sedentary, thereby worsening and accelerating the effects of aging. The central system that is responsible for the beneficial effects of mobility on brain function, cardiac function, metabolism, and other organs is the musculoskeletal system. Without muscle contraction and bone movement, there is no exercise and therefore no beneficial effects on the organism. Exercise appears to delay the negative effects of aging and can ameliorate negative effects of diseases associated with aging. Exercise maintains both muscle and bone mass and it is most likely the maintenance of the health of the musculoskeletal system that is responsible for the health of the organism. The hypothesis to be tested includes: Crosstalk occurs between muscle and bone through systemic factors. The osteocyte is regulated by both mechanical loading and by factors secreted by contracted muscle. In turn, the osteocyte regulates muscle myogenesis and function. Exercise targets the osteocyte and muscle by reducing the negative effects of aging. The specific aims of this program project renewal are 1). Determine how young and old osteocytes regulate myogenesis, muscle mass and function, 2). Determine how muscle protects and maintains osteoblast/osteocyte viability and function, 3). Examine the role of extracellular vesicles in bone-muscle crosstalk, 4). Determine the role of estrogen/β-catenin in muscle-bone crosstalk with aging and 5). Determine if exercise can rescue or reduce the negative effects of aging on bone-muscle crosstalk. These specific aims will be accomplished through a multidisciplinary approach where bone and muscle biologists interact along with engineers and biochemists. This program project focuses on bone-muscle crosstalk utilizing muscle and bone transgenic mouse models, unique bone and muscle cell lines, live cell imaging and intravital imaging capabilities and integration of metabolomics and lipidomics. The projects and their supporting cores are highly integrative and will lead to synergistic interactions where the potential for progress and success is greater than the individual components. Identification of the mechanisms used by muscle and bone to communicate and regulate the musculoskeletal system as a whole and how these are regulated by exercise should lead to interventions for musculoskeletal disease, dysfunction, and disorders and prevent the negative effects of immobilization and aging, not only on the musculoskeletal system, but on the overall health of the individual.

摘要： 我们的社会正变得越来越久坐不动，从而加剧和加速了老龄化的影响。的 中枢系统，负责对脑功能，心脏功能， 代谢和其他器官是肌肉骨骼系统。如果没有肌肉收缩和骨骼运动， 没有锻炼，因此对机体没有有益的影响。运动似乎可以延缓消极的 并且可以改善与衰老相关的疾病的负面影响。运动既能维持 肌肉和骨骼质量，最有可能的是维持肌肉骨骼系统的健康， 对生物体的健康负责。待检验的假设包括： 肌肉和骨骼通过系统因素。骨细胞受机械负荷和某些因素的调节 由收缩的肌肉分泌的。反过来，骨细胞调节肌肉的肌生成和功能。行使 针对骨细胞和肌肉，减少老化的负面影响。该计划的具体目标 项目更新是1）。确定年轻和老年骨细胞如何调节肌生成，肌肉质量和 函数，2）.确定肌肉如何保护和维持成骨细胞/骨细胞的活力和功能， 3）。检查细胞外囊泡在骨-肌肉串扰中的作用，4）。确定的作用 雌激素/β-连环蛋白在肌肉-骨骼串扰中与衰老的关系; 5）.确定运动是否可以拯救或 减少老化对骨骼-肌肉串扰的负面影响。这些具体目标将得到实现 通过多学科的方法，骨骼和肌肉生物学家与工程师沿着互动， 生物化学家本项目主要研究利用肌肉和骨骼的转基因技术， 小鼠模型，独特的骨和肌肉细胞系，活细胞成像和活体成像能力， 代谢组学和脂质组学的整合。项目及其支撑核心高度融合， 将导致协同互动，其中进步和成功的潜力大于个人 件.确定肌肉和骨骼用于沟通和调节肌肉和骨骼的机制。 肌肉骨骼系统作为一个整体，以及如何通过运动调节这些应该导致干预， 肌肉骨骼疾病，功能障碍和障碍，并防止固定的负面影响， 衰老，不仅对肌肉骨骼系统，但对个人的整体健康。