Fig. 11

Role of miR-146a in HFD-induced microglial senescence and the protective effects of elocalcitol. This schematic illustrates the impact of a HFD on miR-146a expression and microglial senescence, as well as the protective effects of elocalcitol treatment. The left side represents the effect of HFD alone, where HFD consumption suppresses miR-146a expression (depicted by the red arrow), which in turn leads to the activation of the TGF-β/SMAD4 pathway. This activation promotes the upregulation of senescence markers (p16, p21), senescence-associated β-galactosidase activity, and the senescence-associated secretory phenotype, contributing to the accumulation of senescent microglia (shown in green with senescence markers and a red halo around them). The right side shows the effects of HFD in combination with elocalcitol treatment. Elocalcitol restores miR-146a expression (depicted by the blue arrow), inhibiting the TGF-β/SMAD4 pathway, and thus reducing the levels of p16 and p21. As a result, SA-βgal activity and SASP are also reduced, which prevents the accumulation of senescent microglia. The microglia are maintained in a non-senescent state (shown with a green outline and no red halo), signifying healthy cellular function. (Created in BioRender. Chithanathan, K. (2024) BioRender.com/w70a352)