Muscle Fatigue and its Impact on Mobility Function in Aging

衰老过程中肌肉疲劳及其对活动功能的影响

基本信息

批准号：
10662460
负责人：
JANE A KENT
金额：
$ 48.26万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
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/10662460
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 clinically relevant cost design experience healthspan human old age (65+)improved in vivo innovation inorganic phosphate neural novel prevent secondary outcome sedentary sex success translational approach young adult

项目摘要

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.

项目概要与年轻人相比，65岁以上的人在高温下会经历更大的肌肉疲劳收缩速度，例如行走时发生的收缩速度。尽管疲劳，或者体力急剧下降最大力量或功率，是骨骼肌的基本特征，是受损的途径细胞能量学、收缩功能和疲劳与年龄相关的活动功能变化仍然存在未知。老年人行动能力下降会增加发病风险和生活质量下降，这反过来又造成巨大的个人和社会负担。老年人的行动障碍是与膝伸肌（KE）功能下降有关。值得注意的是，老年人的 KE 表现出体内氧化能量产生不足，并且与年轻人相比更容易疲劳。一本小说解决 KE 疲劳的临床问题及其对衰老活动能力的影响的方法是确定导致老年人更加疲劳的基本分子和细胞缺陷，以及这些缺陷如何疲劳机制导致活动功能障碍。我们研究的总体目标是提供这种新的知识并缓解人口老龄化导致的流动性下降。我们的中心假设是 KE 老年人，尤其是行动不便的老年人，体内线粒体能量不足产生加剧受损的收缩功能并导致精力充沛时更加疲劳要求较高的工作，包括步行。为了检验这个假设，将在疲劳之前和之后收集数据 30 名健康年轻人（30-40 岁）、30 名健康老年人（70-80 岁）和 30 名老年人（70-80 岁）的高速收缩行动不便的成年人。所有群体都会相对久坐，这将被量化验证使用加速度计。我们将使用集成和转化的方法来构建从分子到行为学，通过测量：使用非侵入性磁共振 (MR) 光谱学进行细胞内能量学；磁共振成像的肌肉形态；单肌纤维钙敏感性和肌球蛋白-肌动蛋白跨桥疲劳条件下的动力学；单纤维和完整肌肉的力-速度关系；降低四肢关节力学、步行的能量消耗、感知的用力和移动任务（椅子上升、平衡）疲劳前后。我们将确定赤字在能源生产（目标 1）和收缩功能（目标 2）在老年人更大的肌肉疲劳中的作用，以及疲劳对步态的影响力学、运输能源成本和流动性（目标 3）。潜在的性别差异将是在每个目标中进行评估。要解决的问题 - 疲劳加剧的原因及其如何影响活动能力在老年人中——实现 NIH 和 NIA 的既定目标。我们的成功将产生重大、积极的影响弥合目前限制我们保持老龄化人口身体健康的能力的现有知识差距活跃且健康。有希望的缓解目标（例如，收缩功能或线粒体方面能量学？）将在未来的研究中确定和追求。