Proteomic analysis reveals that aging rabbit vocal folds are more vulnerable to changes caused by systemic dehydration

Abstract

Background Older adults are more prone to develop systemic dehydration. Systemic dehydration has implications for vocal fold biology by affecting gene and protein expression. The objective of this study was to quantify vocal fold protein changes between two age groups and hydration status, and to investigate the interaction of age and hydration status on protein expression, which has not been investigated in the context of vocal folds before. Comparative proteomics was used to analyze the vocal fold proteome of 6.5-month-old and > 3-year-old rabbits subjected to water ad libitum or water volume restriction protocol. Results Young and older adult rabbits (n = 22) were either euhydrated (water ad libitum) or dehydrated by water volume restriction. Dehydration was confirmed by body weight loss of − 5.4% and − 4.6% in young and older groups, respectively, and a 1.7-fold increase of kidney renin gene expression in the young rabbits. LC-MS/MS identified 2286 proteins in the rabbit vocal folds of young and older adult rabbits combined. Of these, 177, 169, and 81 proteins were significantly (p ≤ 0.05) affected by age, hydration status, or the interaction of both factors, respectively. Analysis of the interaction effect revealed 32 proteins with opposite change patterns after dehydration between older and young rabbit vocal folds, while 31 proteins were differentially regulated only in the older adult rabbits and ten only in the young rabbits in response to systemic dehydration. The magnitude of changes for either up or downregulated proteins was higher in the older rabbits. These proteins are predominantly related to structural components of the extracellular matrix and muscle layer, suggesting a disturbance in the viscoelastic properties of aging vocal fold tissue, especially when subjected to systemic dehydration. Conclusions Water restriction is a laboratory protocol to assess systemic dehydration-related changes in the vocal fold tissue that is translatable to human subjects. Our findings showed a higher number of proteins differentially regulated with a greater magnitude of change in the vocal folds of older adult rabbits in the presence of systemic dehydration compared to younger rabbits. The association of these proteins with vocal fold structure and biomechanical properties suggests that older human subjects may be more vulnerable to the effects of systemic dehydration on vocal function. The clinical implications of these protein changes warrant more investigation, but age should be taken into consideration when evaluating vocal treatment recommendations that interfere with body fluid balance.

Submicroscopic Changes of Thymus Under Cellular Dehydration

“…Понад 1600 білків були успішно ідентифіковані у всіх зразках голосових складок. Зниження регуляції білків, що беруть участь у мітохондріальному метаболізмі в голосових складках, свідчить про механізм запобігання окисного стресу, пов'язаного із системною дегідратацією [6,16].…”

Impact of Rehydration Following Systemic Dehydration on Vocal Fold Gene Expression

“…Here we have used the rabbit, a validated model for laryngeal histology and surgical training, 8,9 and an established model of systemic dehydration in our previous studies. [10][11][12][13] Through nonhuman in vivo studies, our research group has been building mounting evidence that molecular changes result from dehydration. 10,[12][13][14][15][16][17][18] In contrast to the detrimental effects of dehydration, evidence for the benefit of remedial rehydration is limited and inconsistent.…”

“…[10][11][12][13] Through nonhuman in vivo studies, our research group has been building mounting evidence that molecular changes result from dehydration. 10,[12][13][14][15][16][17][18] In contrast to the detrimental effects of dehydration, evidence for the benefit of remedial rehydration is limited and inconsistent. The existing data are largely restricted to acoustic and aerodynamic measures and subjective reports of improved perceived phonatory effort, sometimes noted for potentially limited sensitivity in this application.…”

“…Animal models are, therefore, an attractive substitute allowing a more comprehensive interrogation of the biology underlying the impact of dehydration on the vocal folds. Here we have used the rabbit, a validated model for laryngeal histology and surgical training, 8,9 and an established model of systemic dehydration in our previous studies 10–13 . Through nonhuman in vivo studies, our research group has been building mounting evidence that molecular changes result from dehydration 10,12–18 …”

“…Here we have used the rabbit, a validated model for laryngeal histology and surgical training, 8,9 and an established model of systemic dehydration in our previous studies 10–13 . Through nonhuman in vivo studies, our research group has been building mounting evidence that molecular changes result from dehydration 10,12–18 …”