Bioenergetic Mechanisms of Tongue Muscle Fatigue

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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.