Bioenergetic Mechanisms of Tongue Muscle Fatigue

舌肌疲劳的生物能机制

• 批准号: 9974502
• 负责人: NADINE P CONNOR
• 金额: $ 41.2万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9974502
• 关键词: Acute; Address; Affect; Age; Aging; Analysis of Covariance; Animal Model; Animals; Behavior; Behavior Therapy; Behavioral; Behavioral Assay; Bioenergetics; Biological; Biological Assay; Biomechanics; Blood capillaries; Blood flow; Censuses; Cephalic; Characteristics; Clinical Research; Clinical Trials; Consumption; Data; Deglutition; Deglutition Disorders; Eating; Effectiveness; Elderly; Ethics; Etiology; Exercise; Failure; Fatigue; Food; Functional disorder; Head and Neck Muscle; Head and neck structure; Human; Hypoglossal nerve structure; Impairment; Institute of Medicine (U.S.); Intervention; Intervention Trial; Knowledge; Limb structure; Link; Logistic Regressions; Measurement; Measures; Methods; Microcirculation; Modeling; Morphology; Muscle; Muscle Contraction; Muscle Fatigue; Outcome; Output; Pathway interactions; Physiological; Population; Prevalence; Prevention; Process; Property; Quality of life; Rattus; Reporting; Research; Resistance; Running; Skeletal Muscle; Speech; Structure; Testing; Tongue; Translating; Translations; Treatment Efficacy; Work; age related; aged; base; behavioral outcome; clinical practice; clinically relevant; design; effective therapy; exercise intervention; exercise program; experimental study; extensor digitorum; genioglossus muscle; human old age (65+); improved; insight; muscle aging; muscle metabolism; negative affect; neuromuscular; neuromuscular stimulation; preclinical study; remediation; treadmill; treatment optimization; young adult

Fatigue is a characteristic of aging muscles that results from multiple factors including bioenergetic changes that contribute to muscle metabolism. Alterations in bioenergetic properties of tongue muscles likely contribute to age-related swallowing impairments. However, the relationship of tongue muscle bioenergetics to muscle fatigue and the manner in which behavioral treatments, such as exercise, may be optimized are poorly understood. If elucidated, this knowledge will allow improvement of treatment efficacy. Due to our increasing population of people over the age of 65, which will number over 131 million in the US by 2100, efficacious interventions for age-related deglutition deficits are critical. Our global hypothesis is that age-related increases in tongue muscle fatigue are major contributors to deficits in deglutitive function with age. We further hypothesize that tongue exercise can mitigate these fatigue- and age-related deficits. We will gain insight into mechanisms of tongue muscle fatigue by addressing specific hypotheses for each of our aims in a rat model. We will create both mild and moderate levels of tongue muscle fatigue using neuromuscular electrical stimulation prior to performing: 1) physiological assays of muscle contractile function and capillary blood flow; 2) biological assays of muscle bioenergetics; and, 3) behavioral and biomechanical measures of swallowing in young adult and old rats that have undergone tongue (or sham control) exercise. Our tongue exercise program is modeled after those used in current clinical practice. We have 3 specific aims: Aim 1 will test the hypotheses that tongue muscle fatigue increases with age, is exacerbated by fatigue in an age-dependent manner, and is rescued by tongue exercise; Aim 2 will quantify bioenergetic mechanisms of extrinsic and intrinsic tongue muscles to test the hypothesis that biological variables associated with fatigue degrade with aging and normalize with tongue exercise; and Aim 3 will test the hypotheses that deglutition outcomes are negatively affected by aging and fatigue, and are mitigated by tongue exercise. Our neuromuscular model is the first to evaluate adaptation in bioenergetic pathways with age and exercise in muscles of the tongue. The proposed research will provide a new understanding of mechanisms that underlie age-related tongue muscle fatigue from a physiological perspective, the relationship of structural changes to physiological function, and the effectiveness of lingual exercise as an intervention for muscle fatigue. This work is highly significant due to the large and increasing population of aging people who will benefit from treatments optimized in pre-clinical studies to address often-debilitating deglutition impairments.

疲劳是肌肉老化的一个特征，它是由多种因素引起的，包括生物能量的变化 促进肌肉新陈代谢的物质舌头肌肉生物能量特性的改变可能有助于 与年龄有关的吞咽障碍然而，舌肌生物能量学与肌肉的关系 疲劳和行为治疗的方式，如运动，可能是最佳的，是很差的 明白如果得到阐明，这一知识将有助于改善治疗效果。由于我们的增长 到2100年，美国65岁以上的人口将超过1.31亿， 对与年龄有关的吞咽缺陷进行干预至关重要。我们的总体假设是， 在舌头中，肌肉疲劳是随着年龄增长吞咽功能缺陷的主要原因。我们进一步 假设舌头运动可以减轻这些疲劳和年龄相关的缺陷。我们将深入了解 通过解决我们在大鼠模型中的每个目标的特定假设来研究舌肌疲劳的机制。 我们将使用神经肌肉电刺激技术， 在进行以下操作之前进行刺激：1）肌肉收缩功能和毛细血管血流的生理学测定; 2)肌肉生物能量学的生物测定;和，3）吞咽的行为和生物力学测量， 年轻的成年大鼠和老年大鼠进行了舌头（或假对照）运动。我们的舌头锻炼计划 是仿照当前临床实践中使用的那些。我们有3个具体目标：目标1将测试假设 舌肌疲劳随着年龄的增长而增加，疲劳以年龄依赖性的方式加剧， 通过舌头运动拯救;目标2将量化外在和内在舌头的生物能量机制 肌肉来检验与疲劳相关的生物学变量随着年龄的增长而降低的假设， 目标3将测试吞咽结果是负面的假设 受衰老和疲劳的影响，并通过舌头锻炼减轻。我们的神经肌肉模型是第一个 评估生物能量通路随年龄和舌头肌肉锻炼的适应性。拟议 这项研究将提供一个新的理解机制，与年龄相关的舌肌疲劳 从生理学的角度来看，结构变化与生理功能的关系，以及 舌运动作为肌肉疲劳干预的有效性。这项工作是非常重要的，因为 越来越多的老年人将受益于临床前优化的治疗 研究解决经常使人衰弱的吞咽障碍。