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.

疲劳是衰老肌肉的特征，它来自多种因素，包括生物能变化 这有助于肌肉代谢。舌头肌肉生物能特性的改变可能会导致 与年龄有关的吞咽障碍。但是，舌头肌肉生物能力与肌肉的关系 疲劳和行为治疗（例如锻炼）的方式可能优化的方式很差 理解。如果阐明，这些知识将允许提高治疗功效。由于我们的增加 65岁以上的人口，到2100年，美国将超过1.31亿 与年龄相关的脱水缺陷的干预措施至关重要。我们的全球假设是与年龄相关的增加 舌头肌肉疲劳是随着年龄的变性功能缺陷的主要因素。我们进一步 假设舌头运动可以减轻这些与年龄相关的缺陷。我们将深入了解 通过解决大鼠模型中我们每个目标的特定假设，舌肌疲劳的机制。 我们将使用神经肌肉电气产生轻度和中等水平的舌头肌肉疲劳 在执行之前刺激：1）肌肉收缩功能和毛细血管血流的生理测定； 2）肌肉生物能学的生物测定； 3）吞咽的行为和生物力学测量 患有舌头（或假控制）运动的年轻大鼠。我们的舌头运动计划 以当前临床实践中使用的方式进行建模。我们有3个具体目标：AIM 1将检验假设 舌头疲劳随着年龄的增长而增加，以年龄的方式疲劳加剧，并且是 通过舌锻炼救助； AIM 2将量化外在和内在舌头的生物能机制 肌肉检验以下假设：随着衰老和 通过舌头锻炼正常； AIM 3将检验脱水效果的假设是负面的 受衰老和疲劳的影响，并通过舌锻炼减轻。我们的神经肌肉模型是第一个 通过年龄和运动在舌头的肌肉中评估生物能途径的适应性。提议 研究将提供对与年龄有关的舌头肌肉疲劳的基础机制的新理解 从生理角度来看，结构变化与生理功能的关系以及 舌运动作为肌肉疲劳的干预的有效性。由于这项工作非常重要 大量和越来越多的老龄化人群将从临床前优化的治疗中受益 解决经常延长退化障碍的研究。