Bioenergetic Mechanisms of Tongue Muscle Fatigue

舌肌疲劳的生物能机制

• 批准号: 10200761
• 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/10200761
• 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; efficacious intervention; 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，是由包括生物能变化在内的多种因素造成的 有助于肌肉新陈代谢。舌肌生物能特性的改变可能有助于 与年龄相关的吞咽障碍。然而，舌肌生物能学与肌肉的关系 疲劳以及优化运动等行为治疗的方式很差 明白了。如果得到阐明，这些知识将有助于提高治疗效果。由于我们不断增加 到 2100 年，美国 65 岁以上人口将超过 1.31 亿，有效 针对与年龄相关的吞咽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 随着年龄的增长，舌头肌肉疲劳是导致吞咽功能缺陷的主要原因。我们进一步 假设舌头锻炼可以减轻这些与疲劳和年龄相关的缺陷。我们将深入了解 通过在大鼠模型中针对我们每个目标提出具体假设，研究舌肌疲劳的机制。 我们将使用神经肌肉电产生轻度和中度的舌头肌肉疲劳 执行前的刺激： 1) 肌肉收缩功能和毛细血管血流量的生理测定； 2) 肌肉生物能量学的生物学测定； 3）吞咽的行为和生物力学测量 接受过舌头（或假对照）锻炼的年轻成年和老年大鼠。我们的舌头锻炼计划 是根据当前临床实践中使用的那些进行建模的。我们有 3 个具体目标： 目标 1 将检验假设 舌头肌肉疲劳随着年龄的增长而增加，并以与年龄相关的方式因疲劳而加剧，并且 通过舌头锻炼获救；目标 2 将量化外在和内在舌头的生物能量机制 测试与疲劳相关的生物变量会随着年龄的增长而退化的假设 通过舌头锻炼恢复正常；目标 3 将检验吞咽结果为负面的假设 受衰老和疲劳的影响，可以通过舌头锻炼来缓解。我们的神经肌肉模型是第一个 评估生物能量途径随年龄和舌头肌肉锻炼的适应。拟议的 研究将对与年龄相关的舌肌疲劳的机制提供新的认识 从生理学的角度，结构变化与生理功能的关系，以及 语言锻炼作为肌肉疲劳干预措施的有效性。这项工作非常重要，因为 大量且不断增加的老年人口将受益于临床前优化的治疗 解决经常使人衰弱的吞咽障碍的研究。