OSTEOCYTE REGULATION OF BONE/MUSCLE WITH AGING

摘要： 我们的社会变得越来越久坐不动，从而恶化和加速了老龄化的影响。这个 负责活动对大脑功能、心脏功能、 新陈代谢等器官是肌肉骨骼系统。如果没有肌肉收缩和骨骼运动， 没有运动，因此对机体没有任何有益的影响。锻炼似乎可以延缓负面情绪 对衰老的影响，可以减轻与衰老相关的疾病的负面影响。锻炼既能保持健康，又能保持健康 肌肉和骨量，很可能是维持肌肉骨骼系统的健康 对生物体的健康负责。需要检验的假设包括：串扰发生在 肌肉和骨骼通过全身因素。骨细胞受机械负荷和因子的调节。 由收缩的肌肉分泌。反过来，骨细胞调节肌肉的生成和功能。锻炼 通过减少衰老的负面影响，作用于骨细胞和肌肉。这个项目的具体目标是 项目续期为1)。确定年轻和老年骨细胞如何调节肌肉生成、肌肉质量和 功能，2)。确定肌肉如何保护和维持成骨细胞/骨细胞的活性和功能， 3)。检查细胞外小泡在骨-肌肉串扰中的作用，4)。确定的角色 雌激素/β-连环蛋白在肌肉-骨链中的作用随年龄增长而增加。确定锻炼是否可以挽救或 减少老化对骨骼-肌肉串扰的负面影响。这些具体目标将会实现 通过多学科的方法，骨骼和肌肉生物学家与工程师和 生物化学家。这个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能力以及 代谢组学和脂类组学的整合。这些项目及其支持核心是高度一体化的， 将导致协同互动，在这种互动中，进步和成功的潜力大于个人 组件。确定肌肉和骨骼用于沟通和调节的机制 作为一个整体的肌肉骨骼系统以及这些系统是如何被运动调节的应该导致对 肌肉骨骼疾病、功能障碍和紊乱，并防止制动和 衰老，不仅对肌肉骨骼系统，而且对个人的整体健康。

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.