Submandibular gland-specific inflammaging-induced hyposalivation in the male senescence-accelerated mouse prone -1 line (SAM-P1)

Miyagi, Yuta; Kondo, Yusuke; Kusuda, Yuichiro; Hori, Yusuke; Yamazaki, Seiya; Munemasa, Takashi; Mukaibo, Taro; Masaki, Chihiro; Hosokawa, Ryuji

doi:10.1007/s10522-019-09797-3

Cited by 18 publications

(10 citation statements)

References 40 publications

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“…Consistent with a previous report (Miyagi et al 2019), ex vivo SMG flow rate in 10 min decreased in aged mice, and Aqp5 mRNA expression reduced in aged SMG (Appendix Fig. 2A).…”

Section: Discussionsupporting

confidence: 93%

“…As life expectancy increases, oral health care becomes crucial to maintain quality of life (Iwasaki et al 2021), with saliva playing a critical role in maintaining oral health (Dodds et al 2005; Iwasaki et al 2018). Clinical research and animal studies have demonstrated an association between aging and xerostomia, the subjective sensation of dry mouth (Miyagi et al 2019; Proctor and Shaalan 2021). Estimates show that 30% of adults over 65 y have xerostomia (Ship et al 2002).…”

Section: Introductionmentioning

confidence: 99%

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Altered Rheological Properties of Saliva with Aging in Mouse Sublingual Gland

et al. 2022

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Mucin in saliva plays a critical role in the hydration and lubrication of the oral mucosa by retaining water molecules, and its impaired function may be associated with hyposalivation-independent xerostomia. Age-dependent effects on salivary gland function and rheological properties of secreted saliva are not fully understood as aging is a complex and multifactorial process. We aimed to evaluate age-related changes in the rheological properties of saliva and elucidate the underlying mechanism. We performed ex vivo submandibular gland (SMG) and sublingual gland (SLG) perfusion experiments to collect saliva from isolated glands of young (12 wk old) and aged (27 mo old) female C57BL/6J mice and investigate the rheological properties by determining the spinnbarkeit (viscoelasticity). While fluid secretion was comparable in SMG and SLG of both mice, spinnbarkeit showed a significant decrease in SLG saliva of aged mice than that of young mice. There were no significant differences in GalNAc concentration between young and aged SLG saliva. Liquid chromatography/tandem mass spectrometry analysis of SLG saliva revealed that (Hex)1 (HexNAc)1 (NeuAc)1 at m/z 793.31 was the most abundant O-glycan structure in SLG saliva commonly detected in both mice. Lectin staining of salivary gland tissue showed that SLG stained strongly with Maackia amurensis lectin II (MAL II) while Sambucus nigra agglutinin (SNA) stained little, if any, SLG. The messenger RNA expression of St3gal1 that encodes an α-2,3 sialic acid sialyltransferase SIAT4-A showed a decrease in SLG of aged mice, confirmed by a Western blot analysis. Lectin blot analysis in SLG saliva revealed that the relative signal intensity detected by MAL II was significantly lower in aged SLG. Our results suggest that spinnbarkeit decreases in SLG of aging mice due to downregulation of sialic acid linked to α-2,3 sialic acid sialyltransferase expression.

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“…Consistent with a previous report (Miyagi et al 2019), ex vivo SMG flow rate in 10 min decreased in aged mice, and Aqp5 mRNA expression reduced in aged SMG (Appendix Fig. 2A).…”

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Altered Rheological Properties of Saliva with Aging in Mouse Sublingual Gland

et al. 2022

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“…Figure 5 summarizes current and future treatment aiming at AQPs to treat xerostomia. Agedness induces a gradual decline in saliva production in humans, mice and rats [116][117][118]. In addition, agedness was reported to induce a decrease in AQP5 levels [117][118][119] and in acetylcholineinduced increase in AQP5 levels, independent of a modification in M3R number [120].…”

Section: Therapeutic Strategies Aiming At Aqps To Treat Xerostomiamentioning

confidence: 99%

Insight into Salivary Gland Aquaporins

D’Agostino

Elkashty

Chivasso

et al. 2020

Cells

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The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.

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“…As with many organs, the SGs become less functional with age. Significant age-related decreases are evident in both unstimulated and stimulated saliva secretion in humans [35], and murine models have shown that the stimulated salivary flow rate decreases from 30 weeks of age [36], a result phenocopied in a senescence-accelerated murine model of ageing [37] and mediated by the p16/Ink4a pathway [38]. With increasing age, acinar cells decline and are replaced by adipose tissue and extracellular matrix (ECM) [39].…”

Section: Ageingmentioning

confidence: 99%