Response of aging intrinsic laryngeal muscles to chronic electrical stimulation

This application is in response to the NIH Research Research Project Grant (Parent R01) (PA-10-067). As individuals age, muscle weakness and the development of neuromuscular disorders have the potential to severely diminish the quality of one's life. The larynx is part of a complex sensorimotor system that serves as both a vibratory source for phonation and as a regulatory valving mechanism that protects the airway from the incursion of foreign bodies and food. In the elderly, age-related changes in the laryngeal muscles may compromise voice quality, impairing the ability of individuals to communicate and diminishing their ability to remain socially active and engaged. More significantly, laryngeal muscle dysfunction may contribute to the emergence of dysphagia and subsequent increases in the risk of aspiration, factors that contribute to higher rates of mortality and morbidity. Our preliminary findings indicate that the intrinsic laryngeal muscles have a unique phenotype that is significantly altered by age. More specifically, therapies for certain voice disorders contend to use common principles of skeletal muscle rehabilitation in the hope of increasing muscle mass, strength, and endurance. However, the rationale and applicability of limb muscle rehabilitation concepts to the laryngeal muscles has not been empirically tested. Therefore, this project has three principle objectives:(1) to use chronic electrical stimulation as a fictive endurance "exercise" program in aging rat laryngeal muscle; (2) to characterize the morphological changes consequent to electrical stimulation; and (3) to provide the background to eventually extend these findings to clinical treatments with humans regarding vocal exercises. We will test the central hypothesis that the physiology of aged laryngeal muscle can be modified as a function of chronically enduced activity using the Fisher 344-Brown Norway F1 hybrid rat model of aging. We will examine to what extent chronic high-frequency electrical stimulation remodels the aging posterior cricoarytenoid (PCA, vocal fold abductor) and thyoarytenoid (TA, vocal fold adductor) layngeal muscles. Specific Aim I will examine the effects of chronic electrical stimulation on muscle morphology in aging PCA and TA. Specific Aim 2 will test whether chronic stimulation modifies the metabolic capacity in the aging PCA and TA muscles. Specific Aim 3 will determine to what extent chronic nerve stimulation will reverse functional denervation in aging laryngeal muscles. These studies will be a first test of the applicability of limb muscle rehabilitation interventions intended to reverse age-related dysfunction in the laryngeal muscles. This project will generate novel data to assist in the development of interventions aimed at preventing or reversing agerelated dysfunction in the human larynx, and provide a first step toward testing the efficacy and legitamicy of current voice disorder interventions. Project