Single Skeletal Muscle Fiber Mechanics and Myosin Kinetics in Human Aging

人类衰老过程中的单骨骼肌纤维力学和肌球蛋白动力学

• 批准号: 7917212
• 负责人: Mark Stuart Miller
• 金额: $ 12.27万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7917212
• 关键词: Actins; Address; Affect; Age; Aging; Basic Science; Binding; Biochemical; Clinical Research; Defect; Depressed mood; Disease; Elderly; Elderly man; Engineering; Environment; Exhibits; Fiber; Functional disorder; Goals; Head; Human; Kinetics; Laboratories; Life Style; Mechanics; Mentored Research Scientist Development Award; Molecular; Muscle; Muscle Fibers; Myofibrils; Myosin ATPase; Myosin Heavy Chains; Performance; Physiology; Postdoctoral Fellow; Production; Proteins; Research; Research Personnel; Research Project Grants; Research Training; Skeletal Muscle; Skin; Techniques; Testing; Thick; Thin Filament; Time; Training Programs; Universities; Vermont; Woman; age effect; age related; base; density; novel; programs; protein expression; research study; sarcopenia; single molecule; skills; volunteer

DESCRIPTION (provided by applicant): Project Summary This application for a Mentored Research Scientist Development Award (K01) describes a training program and research project that provides the candidate with the necessary skills and laboratory-based techniques to conduct clinical research studies and to make the transition to an independent researcher. Candidate: The candidate's long term goal is to develop his own research program focusing on the structural and functional alterations in human skeletal muscle that result from aging, disuse and disease. The candidate is a Research Associate at the University of Vermont with a background in engineering. He has, for the first time, applied the novel technique of sinusoidal analysis to single human skeletal muscle fibers; thereby allowing the first examinations of the molecular determinants of contractile function in humans. Environment: The University of Vermont is ideally suited to the candidate's proposed research and training. It includes a cohesive group of clinicians and basic science researchers engaged in clinical research and muscle physiology that examines function at the whole body, whole muscle, single fiber and single molecule levels. Research: The objective of the proposed research study is to characterize the molecular mechanisms underlying age-related changes in single human skeletal muscle fiber function. We hypothesize that aging impairs single fiber function by: 1) altering myosin kinetics (increasing myosin attachment time and decreasing myosin rate of force production) and 2) decreasing myosin heavy chain content. To test these hypotheses, contractile performance and myofibrillar protein expression from single skeletal muscle fibers will be obtained from young (21-35 yrs old) and elderly (65-75 yrs old) volunteers. The proposed studies will represent the first comprehensive examination of the mechanisms underlying human skeletal muscle contractile dysfunction with aging at the molecular level. Relevance: Understanding age-related skeletal muscle contractile dysfunction at the level of the myosin- actin cross-bridge is a necessary step towards developing more effective pharmacological and lifestyle countermeasures to correct sarcopenia that are directed specifically at molecular defects.

描述（由申请人提供）：项目摘要此申请指导研究科学家发展奖（K01）描述了一个培训计划和研究项目，该计划为候选人提供了必要的技能和基于实验室的技术，以进行临床研究并进行临床研究过渡到独立研究人员。候选人：候选人的长期目标是制定自己的研究计划，重点是衰老，废药和疾病导致人类骨骼肌的结构和功能改变。候选人是佛蒙特大学的研究助理，具有工程背景。他首次将正弦分析的新技术应用于单个人体骨骼肌纤维。从而允许对人类收缩功能的分子决定因素进行首次检查。环境：佛蒙特大学非常适合候选人的拟议研究和培训。它包括一组具有临床研究和肌肉生理学的临床医生和基础科学研究人员，这些研究人员检查了整个身体，全肌，单纤维和单分子水平的功能。研究：拟议的研究的目的是表征单个人类骨骼肌纤维功能中与年龄相关的分子机制。我们假设衰老会损害单纤维功能：1）改变肌球蛋白动力学（增加肌球蛋白的附着时间并降低肌球蛋白的力产生速率）和2）降低肌球蛋白重链含量。为了检验这些假设，将从单个骨骼肌纤维的收缩性能和肌原纤维蛋白表达中获得年轻人（21 - 35岁）和老年人（65-75岁）志愿者。拟议的研究将是对人类骨骼肌收缩功能障碍和分子水平衰老的基础机制的首次全面检查。相关性：了解与年龄相关的骨骼肌收缩功能障碍在肌动蛋白杂交桥的水平上是开发更有效的药理学和生活方式对策的必要步骤，以纠正专门针对分子缺损的肌肉减少症。