Abstract
Salivary gland dysfunction induces salivary flow reduction and a dry mouth, and commonly involves oral dysfunction, tooth structure deterioration, and infection through reduced salivation. This study aimed to investigate the impact of aging on the salivary gland by a metabolomics approach in an extensive aging mouse model, SAMP1/Klotho -/- mice. We found that the salivary secretion of SAMP1/Klotho -/- mice was dramatically decreased compared with that of SAMP1/Klotho WT (+/+) mice. Metabolomics profiling analysis showed that the level of acetylcholine was significantly decreased in SAMP1/Klotho -/- mice, although the corresponding levels of acetylcholine precursors, acetyl-CoA and choline, increased. Interestingly, the mRNA and protein expression of choline acetyltransferase (ChAT), which is responsible for catalyzing acetylcholine synthesis, was significantly decreased in SAMP1/Klotho -/- mice. The overexpression of ChAT induced the expression of salivary gland functional markers (α–amylase, ZO-1, and Aqua5) in primary cultured salivary gland cells from SAMP1/Klotho +/+ and -/- mice. In an in vivo study, adeno-associated virus (AAV)-ChAT transduction significantly increased saliva secretion compared with the control in SAMP1/Klotho -/- mice. These results suggest that the dysfunction in acetylcholine biosynthesis induced by ChAT reduction may cause impaired salivary gland function
Highlights
Salivary gland dysfunction is caused by radiation, medications, autoimmune or metabolic diseases, and aging-related degeneration is a common etiology of salivary gland impairment
Zonula occludens-1 (ZO-1), strongly in in the salivary kl -/- mice compared to the control mice. These results demonstrate that choline acetyltransferase (ChAT) parti restores the salivary gland function through regulating the biosynthesis and the choli gic signaling pathway of acetylcholine, suggesting that ChAT may be a potential g therapy for age-related salivary gland dysfunction
A multifactor phenotype that is closely associated with a systemic reduction in body function, is closely associated metabolic alterations
Summary
Salivary gland dysfunction is caused by radiation, medications, autoimmune or metabolic diseases, and aging-related degeneration is a common etiology of salivary gland impairment. Since saliva is primarily produced in acinar cells, salivary gland degeneration can lead to hyposalivation in elderly individuals [3,4]. More recent research has suggested that saliva output in the major glands may diminish with increasing age and may occur with aging-related changes in salivary viscoelasticity in submandibular and sublingual glands [10]. There are conflicting results, a recent meta-analysis suggested that there is an age-related reduction in saliva secretion in resting and stimulated saliva in elderly adults compared with young adults [12]. Population-based studies have demonstrated diminished salivary gland size, saliva volume, and saliva components with increasing age [9,13,14,15]. Aging has been reported to decrease salivary gland function, the fundamental mechanism is not clear
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