OSTEOCYTE REGULATION OF BONE/MUSCLE WITH AGING

骨细胞对骨骼/肌肉衰老的调节

• 批准号: 9789122
• 负责人: Lynda F Bonewald
• 金额: $ 207.7万
• 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/9789122
• 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; 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.

抽象的： 我们的社会变得越来越久坐，从而加剧和加速了老龄化的影响。 负责移动性对大脑功能、心脏功能、 新陈代谢，而其他器官是肌肉骨骼系统，没有肌肉收缩和骨骼运动， 没有锻炼，因此对身体没有有益的影响。锻炼似乎可以延缓负面影响。 运动可以减轻衰老的影响，并可以改善与衰老相关的疾病的负面影响。 肌肉和骨骼质量，很可能是维持肌肉骨骼系统的健康 要测试的假设包括： 串扰发生在之间。 骨细胞通过全身因素调节肌肉和骨骼。 反过来，骨细胞由收缩的肌肉分泌，调节肌肉的肌生成和功能。 该计划的具体目标是通过减少衰老的负面影响来针对骨细胞和肌肉。 项目更新是 1). 确定年轻和年老的骨细胞如何调节肌生成、肌肉质量和 功能，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)。 雌激素/β-连环蛋白与衰老相关的肌肉骨骼串扰，以及 5) 确定运动是否可以缓解或缓解。 减少衰老对骨-肌肉串扰的负面影响将得以实现。 通过多学科方法，骨骼和肌肉生物学家与工程师一起互动， 该项目的重点是利用肌肉和骨骼转基因进行骨-肌肉串扰。 小鼠模型、独特的骨骼和肌肉细胞系、活细胞成像和活体成像功能以及 代谢组学和脂质组学的整合 该项目及其支持核心具有高度的综合性和有效性。 将导致协同互动，其中进步和成功的潜力大于个人 识别肌肉和骨骼用于沟通和调节的机制。 整个肌肉骨骼系统以及如何通过运动调节这些系统应该导致干预措施 肌肉骨骼疾病、功能障碍和紊乱，并防止固定和运动带来的负面影响 衰老不仅影响肌肉骨骼系统，还影响个人的整体健康。