Aging of the Intrinsic Laryngeal Muscles

As the population of the United States grows older, age-induced dysfunction of the different motor systems becomes a more important cause of diminishing quality of life, increasing health costs, and even institutionalization. The larynx is part of a complex motor system that separates the airways from the digestive tract. It protects the airway during swallowing and ventilation, serves as a pressure valve for straining and airway protective reflexes, and is a resonance box for phonation. In the elderly, atrophy and dysfunction of the larynx and its intrinsic musculature compromise voice quality and impair the ability to communicate and remain socially engaged. Laryngeal dysfunction may also cause dysphagia and increase the risk of aspiration. Our preliminary findings indicate that the intrinsic laryngeal muscles are significantly altered by age; unfortunately, the biology of these small muscles has not been systematically studied, and the effects of aging on their function remain largely unknown. Because of their strategic role for ventilation, swallowing and airway protection, it is likely that even small age-related functional deficits in the intrinsic laryngeal muscles may translate to higher morbidity and mortality. In consequence, the objective of this project is to understand the cellular mechanisms that explain the effects of aging on the function of the laryngeal muscles. Combining well-established functional and biochemical assays with the Fischer 344- Brown Norway hybrid rat model of aging, we will determine (1) how age alters the functional characteristics of two key intrinsic laryngeal muscles (posterior cricoarytenoid and thyroarytenoid); (2) how aging alters the cytosolic calcium kinetics of these muscles; and (3) the changes in mitochondrial capacity induced by aging in the intrinsic laryngeal muscles and that may render the muscles more fatigable. We expect that this project will obtain significant new information on the effects of age on laryngeal muscle function, and define the most likely cellular targets for interventions designed to retard, prevent, and even reverse the detrimental effects of the aging process on this hitherto neglected muscle group, of vital importance for a normal and healthy life