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 rt verse-transcriptase polymerase chain reaction (RT-PCR), colla gen subtypes expressed in rat vocal folds were determined, and messenger RN A (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 neona tal, adult, and elderly rats. Collagens: I, III-VIII, XV, XVII, and XVIII a re abundantly expressed, whereas collagens II, IX, X, and XI are absent in rat vocal folds. Messenger RNA levels off collagens I, III, IV, and V and c ollagen-degrading proteinases in the vocal folds of the adult rats are sign ificantly 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 mR NA levels of collagens and V significantly differ from the adult levels. Th ere are no marked age-related alterations in vocal fold levels of TIMP mRNA s, and the tissue variation in the gene expression of the aforementioned mo lecules is minute. Rat vocal folds display tissue-specific expression of co llagen genes. Diminished gene expression for collagens and proteinases and unchanged gene expression for TIMPs indicate a slowdown in collagen turnove r that may increase the cross-linking of collagen molecules. This observati on may explain in part the stiffness that occurs with aging in human vocal folds.