SIRT1-Induced Deacetylation of Akt Expedites Platelet Phagocytosis and Delays Human Endometrial Microvascular Endothelial Cell Aging

Abstract Maintaining the health of endothelium is of critical importance to the prevention against cell aging. The current study was performed to clarify the role of SIRT1 on platelet phagocytosis in cell aging and identified its downstream molecular mechanism. Platelet phagocytosis by human endometrial microvascular endothelial cells (HEMECs) was characterized by transmission electron and fluorescence microscopy. Functional experiments were conducted to examine the platelet phagocytosis and cell aging using the overexpression or knockdown plasmids of SIRT1 and GIRDIN as well as Akt inhibitor and activator. It was found that SIRT1 facilitated platelet phagocytosis by HEMECs, contributing to inhibition of cell aging. Akt activation facilitated platelet phagocytosis and repressed cell aging. GIRDIN overexpression accelerated platelet phagocytosis by HEMECs, leading to delaying of cell aging. GIRDIN phosphorylation at Ser1417 was induced by Akt activation, while activation of Akt was induced by SIRT1-mediated deacetylation, consequently augmenting platelet phagocytosis and delaying cell aging. Taken together, SIRT1 delayed aging of HEMECs by deacetylating Akt, phosphorylating GIRDIN, and inducing platelet phagocytosis. The study highlights a possible target for the prevention of HEMEC aging.