Neuromuscular Healthspan Study: Sarcopenia Intervention

神经肌肉健康寿命研究：肌肉减少症干预

基本信息

批准号：
8457576
负责人：
Ted G Graber
金额：
$ 3.59万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-28 至 2015-02-27
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8457576
关键词：
70-kDa Ribosomal Protein S6 Kinases Activities of Daily Living Address Aftercare Age Aging Animals Appointment Area Attenuated Biochemistry Cell Differentiation process Cell Nucleus Cell Proliferation Cellular biology Collaborations Commit Contractile Proteins Core Facility Elderly Environment Exercise Exercise Physiology Fellowship Fiber Foundations Funding Future Glass Goals Gray unit of radiation dose Health Health Care Costs Healthcare Hypertrophy Immunohistochemistry In Vitro Insulin-Like Growth Factor I Intervention Laboratories Literature Long-Term Care Mass Spectrum Analysis Measurement Measures Mentors Mentorship Messenger RNA Minnesota Morphology Mus Muscle Muscle Fibers Muscle function Myoblasts National Research Service Awards PIK3CG gene Paper Pathway interactions Performance Phosphorylation Physical Function Physiological Physiology Population Positioning Attribute Postdoctoral Fellow Production Protein Biosynthesis Proteins Proteomics Protocols documentation Publishing Quality of life Rattus Recording of previous events Research Research Design Research Infrastructure Research Personnel Resistance Running Scientist Signal Pathway Signal Transduction Skeletal Muscle Societies Soleus Muscle System Technology Testing Training Training Programs Transgenic Animals Translational Research Translations Uncertainty Universities Up-Regulation Variant Weight Weight Lifting Western Blotting Work Writing age effect age related aged autocrine base career cohort cost expectation frailty functional decline grasp improved improved functioning interest medical schools meetings mortality mouse model muscle aging muscle form muscle hypertrophy muscle strength neuromuscular outcome forecast paracrine precursor cell prevent programs retinal rods sarcopenia satellite cell skills statistics strength training success successful intervention undergraduate student wasting

项目摘要

DESCRIPTION (provided by applicant): Sarcopenia, the age-related loss of muscle mass and strength, is a major health concern that contributes to the onset of frailty. Frailty and sarcopeni are major predictors of mortality, poor prognoses and loss of independence. Most importantly, the older adult with sarcopenia and/or frailty has a diminished quality of life. Identifying interventions that prevent, attenuate, and/or reverse the loss of muscle mass and strength will have a significant impact on improving the quality of life, both for basic activities of daily livig and recreational pursuits. The long-term goal of my research is to establish interventions for sarcopenia and frailty. The working hypothesis is that sarcopenia interventions will restore functional ability and extend healthspan. In preliminary work, using a cross-sectional cohort of mice to characterize age-related declines in functional and physiological ability, we developed a Neuromuscular Healthspan Scoring System to evaluate potential treatments. The next step is to test an intervention for sarcopenia. Resistance exercise is a well-accepted treatment for sarcopenia. Hence, the hypothesis for the proposed research is that resistance training will result in improved physical function, strength, and healthspan. This hypothesis will be tested with two Specific Aims: (1) Develop a resistance training model for mice and (2) Determine the effects of a resistance exercise training protocol on functional performance, muscle contractility, muscle remodeling and cellular mechanisms contributing to hypertrophy in adult, old, and aged mice. The main mechanisms to be examined include activation of the PI3k¿Akt¿mTORC1 pathway and satellite cell proliferation. The proposed studies use current technologies and approaches including mass spectrometry, single skeletal muscle fiber physiology, whole muscle physiology, and immunohistochemistry. Both mentors for this proposal, Drs. Thompson and Ferrington, are well-established scientists in the fields of aging, muscle, biochemistry and proteomics, have a strong history of successful mentorship, collaborations, funding and are well published. An advisory team, composed of experts in the fields of statistics, aging, proteomics, myogenic precursor cell biology, translational research and exercise physiology, will provide critical scientific guidance and career advice. The training program is tailored to meet my career goals by providing opportunities to enhance my scientific skill set, interact with established scientists, attend and present at national meetings, write and publish scientific papers, and mentor an undergraduate student. Lastly, the laboratories of my mentors and collaborators, the core facilities and Centers within the Medical School, and at the University of Minnesota will provide an exceptional environment for my training. I am firmly committed to studying aging in my career and will be seeking a post-doctoral position-- ultimately leading to a tenured academic appointment and becoming principle investigator of a lab at a research university. Receiving this F31 NRSA Fellowship will be a significant step towards my future success. PUBLIC HEALTH RELEVANCE: Sarcopenia, the age-related loss of skeletal muscle mass and strength, can ultimately cause the elderly to lose their independence and contribute to the onset of frailty-costing society multi- billions of dollars ($18.5 billion in direct healthcare costs in 000) and decreasing the quality of life of our senior citizens (Jannsen, et al. 2004). It is in the best interest of society, both financially and as a healthspan improvement issue, to find successful interventions for this muscle wasting condition. The overall research focus surrounding this training program is to investigate the effects of aging on skeletal muscle and to develop strategies to mitigate the effects of sarcopenia.

描述（由适用提供）：与年龄相关的肌肉质量和力量损失的肌肉减少症是有助于脆弱发作的主要健康问题。脆弱和肌肉组织是死亡率，预后差和独立丧失的主要预测指标。最重要的是，患有肌肉减少症和/或脆弱的老年人的生活质量降低。确定预防，减弱和/或扭转肌肉质量和力量损失的干预措施将对改善生活质量产生重大影响，包括日常工作和娱乐活动的基本活动。我的研究的长期目标是建立干预肌肉减少症和脆弱的干预措施。工作假设是肌肉减少症干预措施将恢复功能能力并扩展健康范围。在初步工作中，使用小鼠的横截面队列来表征与年龄相关的功能和身体能力下降，我们开发了一种神经肌肉健康范围的评分系统来评估潜在的治疗方法。下一步是测试肌肉减少症的干预措施。耐药性运动是肌肉减少症的良好治疗方法。因此，拟议的研究的假设是，耐药训练将改善身体机能，力量和健康状态。该假设将以两个具体的目的进行检验：（1）为小鼠开发电阻训练模型，（2）确定阻力运动训练方案对功能性能，肌肉收缩性，肌肉的重塑和细胞机制，导致成年，旧小鼠肥大。要研究的主要机制包括激活PI3K¿AKT¿MTORC1途径和卫星细胞增殖。拟议的研究使用当前的技术和方法，包括质谱，单个骨骼肌纤维生理学，整个肌肉生理学和免疫组织化学。该提议的两位导师，博士。汤普森（Thompson）和费林顿（Ferrington）是衰老，肌肉，生物化学和蛋白质组学领域的知名科学家，拥有成功的心态，合作，资助，并发表的悠久历史。一个由统计学，衰老，蛋白质组学，肌原性细胞生物学，翻译研究和运动生理学领域的专家组成的咨询团队将提供关键的科学指导和职业建议。该培训计划是为了实现我的职业目标而量身定制的，这是通过提供机会来增强我的科学技能集，与知名科学家互动，参加并在国家会议上互动，撰写和发表科学论文以及心理专业的本科生。最后，我的导师和合作者，医学院内的核心设施和中心的实验室以及明尼苏达大学的实验室将为我的培训提供杰出的环境。我首先致力于研究职业衰老，并将寻求博士后职位 - 最终导致终身任职任命，并成为一所研究大学实验室的主要调查员。接受此F31 NRSA奖学金将是迈向我未来成功的重要一步。公共卫生相关性：与年龄相关的骨骼肌肉质量和力量损失，最终可能导致老年人失去独立性，并有助于成千上万美元的脆弱社会（185亿美元的直接医疗费用）的成本（000美元以000的直接医疗费用），并降低了我们的老年人的质量，并降低了我们的老年人（Jannsensensense）。最好社会的兴趣在财务上和作为健康范围的改善问题，以寻找肌肉浪费条件的成功干预措施。围绕该培训计划的总体研究重点是研究衰老对骨骼肌的影响，并制定减轻肌肉减少症影响的策略。