Abstract
The current mechanism by which aging reduces salivary secretion is unknown. This study investigates the mechanism of aging-related submandibular (SMG) dysfunction and evaluates the therapeutic potential of dental pulp stem cell-derived exosomes (DPSC-exos). We found that the stimulated salivary flow rate was significantly reduced in naturally aging and D-galactose-induced aging mice (D-gal mice) compared to control mice. Acinar atrophy and periductal fibrosis in SMGs and parotid glands (PGs) were observed in naturally aging and D-gal mice, whereas sublingual glands (SLGs) had no notable alterations. We observed the accumulation of senescent cells in the SMGs, along with a decrease in claudin-3 (Cldn-3) expression and alterations in the distribution of Cldn1 and Cldn3. Additionally, after D-gal-induced senescence of SMG-C6 cells, there was a decrease in paracellular pathway permeability, reduced expression of Cldn3 and occludin, and changes in the distribution of Cldn1, 3, 4, and 7. Furthermore, injecting DPSC-exos into the SMGs of D-gal mice improved stimulated salivary flow rate, reduced acinar atrophy, and decreased SA-β-gal activity. Our study identified that increased senescence of SMGs in aging mice can cause a decrease in salivary secretion by disrupting the expression and distribution of tight junction molecules, and injection of DPSC-exos ameliorates SMG secretory dysfunction. These findings may provide new clues to novel therapeutic targets for aging-related dysfunction of SMGs.