Senescent Expression of Genes Coding Collagens, Collagen-Degrading Metalloproteinases, and Tissue Inhibitors of Metalloproteinases in Rat Vocal Folds: Comparison With Skin and Lungs

In humans, vocal tissue stiffness increases with age, suggesting a possible contribution of age-associated variations in vocal fold collagen turnover to voice senescence. The underlying mechanisms remain to be explored. With the use of reverse-transcriptase polymerase chain reaction (RT-PCR), collagen subtypes expressed in rat vocal folds were determined, and messenger RNA (mRNA) levels of collagens (types I, III, IV, and V), collagen-degrading proteinases (collagenase 3, gelatinase A and B), and tissue inhibitors of metalloproteinases (TIMP-1 to TIMP-4) were measured in vocal folds of neonatal, adult, and elderly rats. Collagens I, III-VIII, XV, XVII, and XVIII are abundantly expressed, whereas collagens II, IX, X, and XI are absent in rat vocal folds. Messenger RNA levels of collagens I, III, IV, and V and collagen-degrading proteinases in the vocal folds of the adult rats are significantly lower than those in the neonates. These mRNA levels show further decline in the vocal folds of the elderly rats, but only the decrease in mRNA levels of collagens I and V significantly differ from the adult levels. There are no marked age-related alterations in vocal fold levels of TIMP mRNAs, and the tissue variation in the gene expression of the aforementioned molecules is minute. Rat vocal folds display tissue-specific expression of collagen genes. Diminished gene expression for collagens and proteinases and unchanged gene expression for TIMPs indicate a slowdown in collagen turnover that may increase the cross-linking of collagen molecules. This observation may explain in part the stiffness that occurs with aging in human vocal folds.