Muscle Regrowth during Physical Rehabilitation and Amino Acid Supplementation

描述（由申请人提供）：本提案的目的是促进候选人在转化和临床研究方面的科学发展，并使其成为康复领域的独立转化科学家。德克萨斯大学医学分支在加尔维斯顿提供了一个优秀的学术和研究环境和基础设施，以促进候选人的教育和培训进行转化研究。 职业目标：该奖项将通过提供一系列正式和非正式的职业发展活动，以及在特殊指导团队的监督下进行动手学习和获取基本初步数据的研究项目，支持候选人从初级研究员成功过渡到中级独立调查员。具体的短期职业目标将包括肌肉代谢、稳定同位素技术和康复研究方面的培训;负责任地开展研究和其他标准科学技能方面的培训;开展研究，以获得实用的临床研究技能和康复科学未来研究应用的初步数据。长期的科学目标是使候选人成为骨骼肌代谢和康复方面的专家，并持续资助医学研究。 研究计划：一般的假设是，在老年人肌肉再生后，急性肌肉骨骼应力将受到积极的影响，传统的物理康复，并进一步加强营养补充。使用最先进的稳定同位素方法研究肌肉代谢和测量细胞信号传导的方法，候选人将测试以下特定假设：（1）全膝关节置换术（TKA）主要通过减少肌肉蛋白质合成诱导急性净蛋白catalysis;（2）TKA诱导catalysis通过摄入必需氨基酸（EAA）减弱;（3）与物理治疗（PT）相结合的EAA补充剂将比安慰剂PT更大程度地刺激肌肉蛋白质合成和mTOR信号传导;（4）TKA PT康复期间的EAA补充剂将比安慰剂PT更大程度地改善肌肉力量、肌肉体积和功能结局。 公益：这项研究将把康复工作的重点放在具体的和目前尚未解决的机制，负责在老年人全膝关节置换术后的肌肉损失。虽然膝关节置换术后骨关节炎引起的膝关节疼痛通常会减轻，但很难完全恢复身体功能和独立性。这项研究将有助于恢复快速增长的膝关节炎老年人的身体功能和独立性。

DESCRIPTION (provided by applicant): The purpose of this proposal is to further the candidate's scientific development in translational and clinical research and to make possible his transition to become an independent translational scientist in rehabilitation. The University of Texas Medical Branch at Galveston provides an outstanding academic and research environment and infrastructure to facilitate the candidate's education and training in the conduct of translational research. Career Goals: This award will support the candidate's successful transition from a junior researcher into a mid level independent investigator by providing an array of formal and informal career development activities, and a research project for hands-on learning and acquisition of essential preliminary data under the supervision of an exceptional mentoring team. The specific short-term career goals will include training in muscle metabolism, stable isotope techniques and rehabilitation research; training in the responsible conduct of research and other standard scientific skills; performance of a research study for the acquisition of practical clinical research skills and of preliminary data for future research applications in rehabilitation science. The long term scientific goal is for the candidate to become an expert in skeletal muscle metabolism and rehabilitation with continuous funding for medical research. Research Plan: The general hypothesis is that in older adults muscle regrowth after an acute musculoskeletal stress will be positively influenced by traditional physical rehabilitation, and further enhanced by nutritional supplementation. Using state-of-the-art stable isotope methodologies for the study of muscle metabolism and methodologies for the measurement of cell signaling, the candidate will test the following specific hypotheses: (1) Total knee arthroplasty (TKA) induces an acute net protein catabolism mainly by reducing muscle protein synthesis; (2) TKA induced catabolism is attenuated by the ingestion of essential amino acids (EAA); (3) EAA supplementation in combination with physical therapy (PT) will stimulate muscle protein synthesis and mTOR signaling to a greater extent than PT with placebo; and (4) EAA supplementation during TKA PT rehabilitation will improve muscle strength, muscle volume and functional outcomes to a greater extent than PT with placebo. Public Benefit: This research will focus rehabilitation efforts on specific and currently unresolved mechanisms responsible for muscle loss following total knee replacement in older adults. While knee pain due to bone arthritis is often alleviated after knee replacement, complete return of physical function and independence is difficult to achieve. This research will help to restore physical function and independence in the rapidly growing population of older adults with knee arthritis.