The Role Of Adjudin In Cellular Senescence And Cerebral Ischemia-Induced Astrogliosis And Its Mechanism

Aging,marked by the physical and functional decline in numerous biological processes,is associated with multiple pathologies including cancer,neurodegenerative diseases and cardio-cerebral vascular diseases.Cellular senescence is closely associated to the disorder and loss of tissue/organ function,which may lead to aging-related disease.Herein we investigated that adjudin,a multi-functional small molecule compound,could delay cellular senescence and inhibit the astrogliosis in the post-acute phase of cerebral ischemia.In the first part,it has been found that adjudin can delay hydroxyurea(HU)-induced senescence in mouse embryo fibroblasts(MEFs).Adjudin could reduce the proportion of senescence-associated ?-galactosidase(SA-?-gal)-positive cells and decrease the expression levels of senescencerelated biomarkers p16 and p21.Mechanistically,adjudin exerted its antisenescence effect by elevating the expression level of Sirt3,which was found to attenuate ROS production through the regulation of Foxo3 a and SOD2.Furthermore,by comparing wildtype and Sirt3-knockout MEFs,we confirmed that Sirt3 indeed mediated the anti-senescence effect of adjudin.In the second part,adjudin could inhibit the astrogliosis induced by injury.In the oxygen and glucose deprivation(OGD)model,adjudin could significantly inhibit the proliferation of reactive astrocytes.In addition,after the treatment of adjudin,the area of wound scratch was larger compared with the control group,which indicated that adjudin could prevent the migration of reactive astrocytes.The mechanism was further explored.It was observed that adjudin could upregulate Sirt3 and Foxo3 a and downregulate Notch1 in both models.Taken together,our findings identify adjudin with a novel anti-aging and protection property that could be exploited for aging-related diseases.