Senescent expression of genes coding tropoelastin, elastase, lysyl oxidase, and tissue inhibitors of metalloproteinases in rat vocal folds: Comparison with skin and lungs

Histology studies indicate that vocal elastin content accumulates with age, suggesting possible contribution of elastin to age-associated voice change s. However, the underlying mechanism remains unclear. Using a reverse-trans criptase polymerase chain reaction (RT-PCR), mRNA levels of tropoelastin, e lastase, lysyl oxidase, and tissue inhibitors of metalloproteinases (TIMP-1 to TIMP-4) were measured in vocal folds, tail skin, and lungs of rats at a ges 1.5 +/- 0.5 weeks (neonatal), 6.0 +/- 0.5 months (adult), and 24 +/- 0. 5 months (elderly). Vocal expression of both tropoelastin and lysyl oxidase peaks during the neonatal stage, followed by a significant decrease. Gene expression for elastase in the vocal Folds of adult rats is not dissimilar to the neonatal levels. The levels in the elderly rats, however, show marke d increase, to as much as 201% of the neonatal levels (p < .05). On the oth er hand, there is no conspicuous age-dependent variation in vocal expressio n of TIMPs. Gene expression of tropoelastin was similar in rat skin, lung, and vocal folds. In summary compared to what is found in adult rats, there is a significant up-regulation in the expression of vocal elastase in the e lderly animals in the presence of unchanged vocal expression of tropoelasti n, lysyl oxidase, and TIMPs. As senescence occurs in both adult and elderly rats, tropoelastin and elastase expression are most affected. Gene express ion for proteins affecting the amount of elastin in the vocal Fold extracel lular matrix does vary with age. These results may not be directly applicab le to humans, because biomechanical forces experienced by human folds are l ikely different than those experienced by rats. However, in the absence of biomechanical forces experienced by humans, rat lungs, skin, and vocal fold s display similar profiles of expression of genes coding the above-mentione d molecules. Similar profiles of expression for elastin genes across differ ent tissue types not sharing similar environments suggests a common mechani sm influencing senescence of these tissues. Human folds likely share a comm on similar mechanism of senescence with other organ systems, although organ -specific factors (oscillation, mechanical forces) are also likely operatin g.