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.