Figure 5.

Model illustrating how TLR9-mediated responses can govern periodontitis pathophysiology during aging. The lifetime activation of TLR9 by nucleic acids triggers the synthesis of inflammatory mediators and DAMPs-like S100 proteins and fosters a deleterious senescence environment characterized by an elevated activity of the β-galactosidase enzyme and p16^INK4a/p19^ARF balance, as well as a boosted inflammaging milieu with higher expression of inflammatory/osteoclast mediators like Cxcl8, Il-6, and Rankl. As a result, macrophages undergo osteoclast differentiation, which leads to alveolar bone resorption and periodontitis progression during aging.