Senescent Cells Implicated in Loss of Salivary Secretion in Aging
Among the many dysfunctions of aging, significant loss of salivary gland activity is one of those that likely never crosses the mind of anyone other than those suffering from or treating its consequences. Nonetheless, the salivary gland is a complex structure, and like all tissues, is negatively impacted by the mechanisms of aging. Inadequate production of saliva and contribute to the difficulties of eating experienced by very old people, as well as alter the oral microbiome in detrimental ways.
As for many aspects of aging, the relative importance of the various mechanisms of aging in salivary gland dysfunction is not known. Today's open access paper focuses on the age-related accumulation of senescent cells, which at this point has been comprehensively demonstrated to contribute to many specific dysfunctions of aging in animal models. Senescent cells secrete inflammatory, disruptive signals. The more senescent cells there are in a tissue, the greater the negative impact on tissue structure and function.
Saliva is essential for maintaining oral health, playing a role in lubrication, taste, chewing, swallowing and initial immune defense. Studies have shown that older people experience decreased salivary secretion, leading to symptoms such as dysphagia, increased risk of dental caries, and dysbiosis of the oral microbiota. Increasing research suggests a strong link between the excessive accumulation of senescent cells and age-related diseases. The accumulation of senescent cells, particularly those positive for p16Ink4a, is associated with inflammatory responses and reduced lifespan. Conversely, the elimination of these cells can attenuate tissue dysfunction and improve health.
Tight junctions, cell-to-cell adhesion complexes located at the apical regions of adjacent epithelial/endothelial cells, dynamically regulate material transport through the paracellular pathway, playing a crucial role in saliva secretion. Recent researches have shown that dysfunction of tight junctions contributes to abnormalities in salivary secretion in diseases such as diabetes mellitus. Numerous studies have demonstrated significant alterations in tight junctions in various tissues and organs during aging, such as the skin, gastrointestinal tract, and blood-brain barrier (BBB).
This study investigates the mechanism of aging-related submandibular 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 submandibular and parotid glands were observed in naturally aging and D-gal mice, whereas sublingual glands had no notable alterations. We observed the accumulation of senescent cells in the submandibular glands.
Injecting DPSC-exos into the submandibular glands 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 submandibular glands 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 submandibular secretory dysfunction. These findings may provide new clues to novel therapeutic targets for aging-related dysfunction of submandibular glands.