Aging-related salivary dysfunction commonly induces the poor oral health, including decreased saliva flow and dental caries. Although the clinical significance of the salivary glands is well-known, the complex metabolic pathways contributing to the aging-dysfunction process are only beginning to be uncovered. Here, we provide a comprehensive overview of the metabolic changes in aging-mediated salivary gland dysfunction as a key aspect of oral physiology. Several metabolic neuropeptides or hormones are involved in causing or contributing to salivary gland dysfunction, including hyposalivation and age-related diseases. Thus, aging-related metabolism holds promise for early diagnosis, increased choice of therapy and the identification of new metabolic pathways that could potentially be targeted in salivary gland dysfunction.
Klotho is a transmembrane protein known to regulate aging and lifespan. Soluble Klotho (sKL), a truncated form of Klotho, regulates various cell signaling pathways, including bone development. Here, we investigated the relationship between sKL and the zinc finger transcription factor early growth response protein 1 (EGR-1) on bone formation. We find that sKL induces the expression of EGR-1 mRNA and protein. Through mutational analysis, we identify the 130 bp region on the EGR-1 promoter that is responsive to sKL overexpression. Additionally, sKL induces the expression of markers of bone differentiation (BMP2, RUNX2, ALP, COL1A, and osteocalcin) in osteoblast MC3T3 cells. EGR-1 siRNA decreases the bone mineralization induced by sKL or ascorbic acid/glycerol 2-phosphate in MC3T3 cells. Our results suggest that sKL may regulate bone development through EGR-1 expression.
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
Designed experimental setup, and a prototype of the original devices for athermic relaxation of thermal residual stresses in openwork welded constructions of large dimensions for the rational use of energy high-frequency acoustic (ultrasonic) fields, conducted laboratory studies and pilot tests in real conditions of production. Ultrasonic relaxation when welding thin-walled constructions standard openwork rolled steel profiles 10 large dimensions (up to 3 x 10 m). It has been established that with a decrease in the time of ultrasonic relaxation, the efficiency of its use decreases somewhat. Therefore, in an industrial environment, it is advisable to use the duration of ultrasonic treatment in the range of 0.02-0.04 min per mm of weld length.
The results of the study of the effectiveness of high-speed ultrasonic turning of billets from heat-resistant nickel alloys without coolant are given. It was established that the introduction of ultrasonic field energy into the shaping zone reduces the contact temperature by 10–15% and the cutting force by 20–30%. However, this does not cause a decrease in metal removal performance due to a significant loss of strength and ease of cutting at temperatures above 800 C. As follows from the results, ultrasound helps to reduce the thickness of the defective layer, the formation of which is caused by thermal processes and phase transformations with the appearance of tensile residual stresses in the surface layer.
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