BIOLOGICAL MECHANISMS FOR VOCAL SENESCENCE

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The production of voice involves both mitotic and post-mitotic tissue. The lamina propria and epithelium are mitotic tissues, while the neuromotor tissues are non-mitotic. Senescence of the human organism may be controlled by fundamental molecular mechanisms. The most popular of the proposed molecular mechanisms that may influence senescence are the 1) telomere shortening theory and 2) the instability of the human genome theory (also referred to as the DNA degradation or contamination theory.) Although much research supports these two theories in animal and cellular studies, no studies have shown these two theories to be operative in humans. Somewhat inherent in these two mechanisms (explained later in the proposal) is that the telomere shortening theory probably affects mitotic tissue senescence and the genome instability theory affects non-mitotic tissue senescence. The voice, being a composite of both types of tissues, may represent a unique window in which to observe the aging or senescence process of the human organism. About 500 individuals in 47 families involving 3 generations will be the subjects of this research. These families are the same families which make up the Human Genome Project started in 1984. These families are extensively genotyped, some with over 10,000 known genotypes. In this proposed study, actual individual rates of telomere shortening and DNA degradation will be correlated with vocal characteristics of age. Furthermore, this study will examine measures of senescence of other organ systems such as respiratory system, central nervous system, endocrine system, connective tissue and musculoskeletal system. Measures of senescence of these organ systems will be compared to characteristics of vocal senescence to see how these measures co- vary together. This will allow us to determine what organ systems and tissues age similar to voice and possibly will give us clues as to fundamental mechanisms of senescence. Lastly, through pedigree analysis of these families, gene linkage studies will be performed to determine loci for genes that may control senescence of voice and possible other organs or tissues.