Adiponectin is associated with inflammaging and age-related salivary gland lipid accumulation

Abstract

Dry mouth is frequently observed in the elderly, and enhanced lipid accumulation plays a critical role in cellular senescence in the salivary gland (SG). We investigated the mechanisms that mediate lipogenesis-associated SG senescence. Adult (28.6 ± 6.6 y.o. and 43.3 ± 1.5 y.o.) and aged (82.0 ± 4.3 y.o. and 88.0 ± 4.3 y.o.) human parotid and submandibular glands were compared with respect to histologic findings, 8-OHdG (8-hydroxy 2 deoxyguanosine) expression patterns, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) and SA-β-gal (senescence-associated β-galactosidase) assay results. Also, microarray analysis was performed on RNA extracted from adult and aged SG to identify DEGs (differentially expressed genes). The effects of silencing ADIPOQ (Adiponectin) were evaluated by quantifying cell proliferation, immunohistochemical staining for cellular senescence and inflammation-associated proteins, SA-β-gal assays, RT-PCR, and western blot. Histological findings demonstrated the presence of more lipocytes, chronic inflammation, fibrosis, and lymphocytic infiltration in old SG. In addition, old tissues demonstrated higher expressions of SA-β-gal, more apoptotic cells in TUNEL assays, and higher oxidative stress by 8-OHdG immunostaining. Microarray analysis showed lipogenesis was significantly upregulated in old tissues. Silencing of ADIPOQ (a lipogenesis-related gene) reduced inflammation and SA-β-gal levels and increased cell proliferation and the expressions of amylase and aquaporin 5 in human SG epithelial cells. The study shows ADIPOQ is a potential target molecule for the modulation of lipogenesis associated with SG senescence.

Gemigliptin Improves Salivary Gland Dysfunction in D-Galactose-Injected Aging Rats

“…The age-related reduction in secretory cells in salivary glands is thought to be the result of decreased cell proliferation or increased cell death [ 39 ]. Consistent with our results, age-related reduction in acinar cell area has also been observed in human salivary glands [ 40 ]. Salivary gland dysfunction-induced mice showed a decrease in acinar area and an increase in duct area in both male and female mice [ 41 , 42 ].…”

Senescence and fibrosis in salivary gland aging and disease

“…Another study found an increase in Adiponectin (ADIPOQ) and lipogenesis-associated senescence in aged relative to young adult human submandibular salivary glands (SMG) and parotid glands. 61 Silencing of ADIPOQ in human SG epithelial cells in this study reduced SA-β-Gal and inflammation while increasing expression of acinar genes, amylase and aquaporin 5, suggesting a link between lipogenesis-associated senescence and salivary hypofunction.…”

“… 73 Indeed, senolytics have demonstrated efficacy in reducing pathological burden in diverse tissues and organisms to delay tissue degeneration and improve tissue function. 55 , 61 , 74 , 75 For example, treatment with the senolytic drugs, dasatinib and quercetin, improved lung function in idiopathic pulmonary fibrosis (IPF) lung models in mice 55 and has had promising results in treating human disease. 76 Murine models that harnessed the activity of p16 INK4A to abate senescence were shown to limit age-related declines in cognitive, adipose, cardiac, and renal function, 77 demonstrating the benefit of senescence abatement to age-related loss of organ function.…”

Relationship between chronic obstructive pulmonary disease and adiponectin concentrations: An updated meta-analysis and single-cell RNA sequencing

“…van den Borst et al [ 47 ] showed that increased visceral fat mass might be an important factor in low-grade systemic inflammation, and in COPD patients and healthy controls with comparable whole-body fat mass, the visceral fat area is increased, and plasma adiponectin levels are elevated among old aged patients. Kim JW [ 61 ] proved the association of adiponectin with inflammation and age-related lipid deposition in the salivary gland and that silencing of ADIPOQ decreased SA-β-gal and inflammation in the salivary gland epithelium, suggesting that cellular senescence is regulated by the adiponectin gene. Subsequently, a subgroup analysis was conducted according to sample type, study design type, and assay method, and serum/plasma adiponectin levels remained high in COPD patients.…”