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 changes. However, the underlying mechanism remains unclear. Using a reverse-transcriptase polymerase chain reaction (RT-PCR), mRNA levels of tropoelastin, elastase, lysyl oxidase, and tissue inhibitors of metalloproteinases (TIMP-1 to TIMP-4) were measured in vocal folds, tail skin, and lungs of rats at ages 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 rots, however, show marked increase, to as much as 201% of the neonatal levels (p < .05). On the other hand, there is no conspicuous age-dependent variation in vocal expression 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 elderly animals in the presence of unchanged vocal expression of tropoelastin, lysyl oxidase, and TIMPs. As senescence occurs in both adult and elderly rats, tropoelastin and elastase expression are most affected. Gene expression for proteins affecting the amount of elastin in the vocal fold extracellular matrix does vary with age. These results may not be directly applicable to humans, because biomechanical forces experienced by human folds are likely different than those experienced by rats. However, in the absence of biomechanical forces experienced by humans, rat lungs, skin, and vocal folds display similar profiles of expression of genes coding the above-mentioned molecules. Similar profiles of expression for elastin genes across different tissue types not sharing similar environments suggests a common mechanism influencing senescence of these tissues. Human folds likely share a common similar mechanism of senescence with other organ systems, although organ-specific factors (oscillation, mechanical forces) are also likely operating.
Ding
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Department of Pathology, College of Medicine, University of Utah, Salt Lake City, USA.
Gray
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SD
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D008168:Lung / Q000378:metabolism*; D008297:Male; D010196:Pancreatic Elastase / Q000235:genetics* / Q000378:metabolism*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics* / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics* / Q000378:metabolism*; D014333:Tropoelastin / Q000235:genetics* / Q000378:metabolism*; D014827:Vocal Cords / Q000378:metabolism*
D017931:DNA Primers; D018076:DNA, Complementary; D019714:Tissue Inhibitor of Metalloproteinases; D014333:Tropoelastin; D012313:RNA; D008249:Protein-Lysine 6-Oxidase; D010196:Pancreatic Elastase