The elderly suffer from age-related swallowing and voice disorders. This project will provide the first statistically unbiased quantitative data concerning the pathogenetic mechanisms underlying age-related laryngeal dysfunction and will thereby contribute to a logical basis for improved methods of prevention, diagnosis and treatment of these conditions. Human tissues will be obtained from autopsy and laryngectomy cases and will include selected sensory and motor systems that are crucial to the laryngeal protective reflex and the voice. Specific data concerning the pathogenesis of these dysfunctions in man is essential since the role of the larynx is not sufficiently analogous in any animal model. In addition, conventional biochemical techniques are not applicable since the relevant parameters vary greatly within a mosaic of functionally distinct, highly specialized cell types and even within subcellular compartments. These difficult technical problems will be addressed by using ultrastructural, histochemical and immunocytochemical techniques in conjunction with stereological techniques (3-dimensional quantitative morphological data based on geometrical probability). These methods provide the only means to obtain statistically unbiased, quantitative, correlative data on age-related cellular loss and metabolic disruptions in cellular and subcellular compartments in sufficiently large samples of specific cell types in human laryngeal tissues. The role of the following parameters in the pathogenetic mechanisms underlying age-related laryngeal dysfunction will be assessed: 1. The extent and cell type specificity of nerve fiber, muscle fiber and sensory receptor loss and cellular atrophy in the recurrent and superior laryngeal nerves, thyroarytenoid muscle and epiglottis, respectively. 2. The capacity for support of cellular energy pools via oxidative metabolism in specific cell types in the thyroarytenoid muscle, superior and recurrent laryngeal nerves and sensory receptors in the epiglottis. 3. The role of changes in the cellular determinant of the contraction speed in the thyroarytenoid muscle. 4. The role of changes in the cellular determinant of the axon diameter and of the conduction velocity in the superior and recurrent laryngeal nerves. In addition, these data will provide age- matched normative baselines for future studies of other pathological conditions and will contribute to the understanding of the basic metabolic, structural and topographical specializations that determine human laryngeal function.
| Malmgren, L T; Jones, C E; Bookman, L M (2001) Muscle fiber and satellite cell apoptosis in the aging human thyroarytenoid muscle: a stereological study with confocal laser scanning microscopy. Otolaryngol Head Neck Surg 125:34-9 |
| Malmgren, L T; Fisher, P J; Jones, C E et al. (2000) Numerical densities of myonuclei and satellite cells in muscle fiber types in the aging human thyroarytenoid muscle: an immunohistochemical and stereological study using confocal laser scanning microscopy. Otolaryngol Head Neck Surg 123:377-84 |
| Malmgren, L T; Lovice, D B; Kaufman, M R (2000) Age-related changes in muscle fiber regeneration in the human thyroarytenoid muscle. Arch Otolaryngol Head Neck Surg 126:851-6 |
| Malmgren, L T; Fisher, P J; Bookman, L M et al. (1999) Age-related changes in muscle fiber types in the human thyroarytenoid muscle: an immunohistochemical and stereological study using confocal laser scanning microscopy. Otolaryngol Head Neck Surg 121:441-51 |
