Muscle Fatigue and Mobility Function in Aging - MR-compatible ergometer

衰老过程中的肌肉疲劳和活动功能 - MR 兼容测力计

• 批准号: 10654212
• 负责人: JANE A KENT
• 金额: $ 3.95万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10654212
• 关键词: Accelerometer; Actins; Acute; Address; Adult; Aging; Anatomy; Basic Science; Behavioral; Bilateral; Biopsy; Calcium; Characteristics; Clinical; Data; Elderly; Equilibrium; Exertion; Exhibits; Extensor; Failure; Fatigue; Fiber; Frequencies; Functional disorder; Future; Gait; Goals; Hip region structure; Impairment; In Vitro; Joints; Kinetics; Knee; Knowledge; Lead; Lower Extremity; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Mechanics; Metabolic; Methods; Mission; Mitochondria; Molecular; Monitor; Morbidity - disease rate; Morphology; Movement; Muscle; Muscle Contraction; Muscle Fatigue; Muscle Fibers; Muscle function; Myosin ATPase; Outcome; Participant; Pathway interactions; Persons; Phosphorus; Physical activity; Population; Production; Property; Protocols documentation; Protons; Public Health; Quality of life; Rehabilitation therapy; Relaxation; Research; Risk; Role; Skeletal Muscle; Testing; Therapeutic Intervention; Time; Torque; Translations; United States National Institutes of Health; Walking; Work; age related; aged; aging population; base; behavior measurement; clinically relevant; cost; design; experience; healthspan; human old age (65+); improved; in vivo; innovation; inorganic phosphate; novel; prevent; relating to nervous system; secondary outcome; sedentary; sex; success; translational approach; young adult

PROJECT SUMMARY Compared with young adults, people over the age of 65 years experience greater muscle fatigue at high contraction velocities, such as those that occur during walking. Although fatigue, or the acute decrease in maximal force or power, is a fundamental characteristic of skeletal muscle, the pathway from impaired cellular energetics, contractile function and fatigue to age-related changes in mobility function remains unknown. Mobility reduction in older adults carries an increased risk for morbidities and a poor quality of life, which in turn creates tremendous personal and societal burdens. Mobility dysfunction in older adults is associated with decrements in knee extensor muscle (KE) function. Notably, the KE of older adults exhibit a deficit in oxidative energy production in vivo, as well as greater fatigue compared with young adults. A novel means to address the clinical problem of KE fatigue and its impact on mobility in aging is to determine the fundamental molecular and cellular deficits that contribute to greater fatigue in older adults, and how these fatigue mechanisms lead to mobility dysfunction. The overall goal of our research is to provide this new knowledge and mitigate decreased mobility in our aging population. Our central hypothesis is that the KE of older adults, particularly those with mobility dysfunction, will have deficits of in vivo mitochondrial energy production that exacerbate impaired contractile function and result in greater fatigue during energetically- demanding work, including walking. To test this hypothesis, data will be gathered before and after fatiguing high-velocity contractions in 30 healthy young (30-40 yr), 30 healthy older (70-80) and 30 older (70-80) adults with mobility impairment. All groups will be relatively sedentary, which will be verified quantitatively using accelerometry. We will use an integrated and translational approach to build from the molecular to the behavioral, by measuring: intracellular energetics using non-invasive magnetic resonance (MR) spectrosopy; muscle morphology by MR imaging; single muscle fiber calcium sensitivity and myosin-actin cross-bridge kinetics during fatigue conditions; force-velocity relationships of single fibers and intact muscle; lower extremity joint mechanics, the energy cost of walking, perceived exertion and mobility tasks (chair rises, balance) before and after fatigue. We will determine the role of deficits in both energy production (Aim 1) and contractile function (Aim 2) in the greater muscle fatigue of older adults, as well as the impact of fatigue on gait mechanics, the energy cost of transport, and mobility (Aim 3). Potential sex-based differences will be evaluated in each Aim. The problem to be addressed- the causes of greater fatigue and how it impacts mobility in older adults- tackles stated goals of the NIH and NIA. Our success will have a significant, positive impact by bridging an existing knowledge gap that currently limits our ability to keep our aging population physically active and healthy. Promising targets for mitigation (e.g., aspects of contractile function or mitochondrial energetics?) will be identified and pursued in future studies.

项目摘要 与年轻人相比，65岁以上的人在高肌肉疲劳时经历更大的肌肉疲劳 收缩速度，例如在步行过程中发生的速度。虽然疲劳或急性减少 最大力或力量是骨骼肌的基本特征，这是受损的途径 蜂窝能量学，收缩功能和疲劳与年龄相关的活动功能的变化仍然存在 未知。老年人的流动性降低会增加病毒性和生活质量差的风险， 反过来，这造成了巨大的个人和社会负担。老年人的移动功能障碍是 与膝盖伸肌（KE）功能的减小有关。值得注意的是，老年人的KE表现出 与年轻人相比，体内氧化能量产生的不足以及更大的疲劳。小说 解决KE疲劳的临床问题及其对衰老中流动性的影响的方法是确定 基本的分子和细胞缺陷，导致老年人更大的疲劳，以及如何 疲劳机制会导致活动障碍。我们研究的总体目标是提供这个新的 知识和减轻我们老龄化人口的流动性降低。我们的中心假设是 老年人，尤其是患有迁移障碍的老年人，会出现体内线粒体能量的缺陷 加剧收缩功能的生产会加剧，并在能量上导致更大的疲劳 苛刻的工作，包括步行。为了检验该假设，将在疲劳之前和之后收集数据 30名健康的年轻人（30 - 40年），30个健康年龄较大（70-80）和30岁（70-80）的高速收缩（70-80） 运动障碍的成年人。所有组将相对久坐，将进行定量验证 使用加速度计。我们将使用综合和翻译的方法从分子到 行为，通过测量：使用非侵入性磁共振（MR）光谱的细胞内能量； MR成像的肌肉形态；单肌纤维钙敏感性和肌球蛋白 - 肌动蛋白杂交桥 疲劳状况下的动力学；单纤维和完整肌肉的力关系；降低 肢体机制，步行，感知的劳纳和流动任务的能源成本（椅子上升， 平衡）疲劳前后。我们将确定缺陷在能源生产中的作用（AIM 1）和 收缩功能（AIM 2）在老年人的肌肉疲劳中以及疲劳对步态的影响 力学，运输的能源成本和流动性（AIM 3）。潜在的基于性别的差异将是 在每个目标中进行评估。要解决的问题 - 造成更大疲劳的原因及其如何影响流动性 在老年人中，铲球指出了NIH和NIA的目标。我们的成功将对 弥合现有的知识差距，该差距目前限制我们保持人口老龄化的能力 活跃健康。有希望的缓解目标（例如，收缩功能或线粒体方面 能量吗？）将在未来的研究中被识别和追求。