EXCEED THE SPACE PROVIDED. Fatigue and weakness are common complaints of elderly people related to sarcopenia, or the loss of skeletal muscle mass, organization, and strength. Little is known concerning the pathophysiology and age-related sequelae of sarcopenia in muscles of the head and neck. The tongue has a vital role in speech and swallowing, and poor lingual control is associated with both speech and swallowing impairment. The main hypothesis of this work is that age-related alterations in tongue function are based upon naturally occurring denervation-reinnervation processes, and these processes can be reversed or prevented via exercise. We will test this hypothesis in a rat model by comparing physiological, biochemical, and histological parameters of old rat tongue muscles with young muscles, and with old tongue muscles that have undergone exercise. The proposed research has 2 specific aims: (1) To quantify changes in neuromuscular structure predictive of age-related tongue weakness; and (2) To determine underlying neuromuscular changes induced by tongue exercise in old rats. Physiological experiments will be performed in vivo in young and old rats. In the same animals, biochemical analyses of myosin heavy chain composition, and histological analyses of neuromuscular junctions will be performed. Two conditions will be employed in Specific Aim 2: (1) Progressive Resistance Training - rats will be trained to press the tongue against a disk with progressively increasing load resistance, or (2) Stimulation - bilateral chronic stimulation of the hypoglossal nerves. Inclusion of these two conditions allows us to examine neuromuscular changes associated with increased activation of nerve-muscle connections, and also exercise-related phenomena influenced by the larger sensorimotor circuit activated by exercise. Analyses of covariance (a combination of analysis of variance and regression) will be used to determine the degree to which muscle contractile properties can be predicted from biochemical and histological characteristics. Further analyses of variance will be performed to compare the physiological, biochemical, and histological variables of interest as a function of age group (Specific Aim 1) or age by exercise condition (Specific Aim 2). This work is innovative and important in establishing potential morphological bases for the alterations in physiological function observed with tongue muscle senescence. Further, this work will be highly significant in discovering a neuromuscular basis for the putative benefits of exercise in the prevention and treatment of age-related speech and swallowing impairment. PERFORMANCE SITE ========================================Section End===========================================
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