The rapidly increasing prevalence of diabetes mellitus worldwide is one of the most serious and challenging health problems in the 21st century. Mammalian sirtuin 1 （SIRT1） has been shown to decrease high-glucose-induced endothelial cell senescence in vitro and prevent hyperglycemia-induced vascular dysfunction. However, a role for SIRTI in prevention of hyperglyce- mia-induced vascular cell senescence in vivo remains unclear. We used endothelium-specific SIRT1 transgenic （SIRT1-Tg） mice and wild-type （WT） mice to construct a 40-week streptozotocin （STZ）-induced diabetic mouse model. In this mode, 42.9% of wild-type （WT） mice and 38.5% of SIRT1-Tg mice were successfully established as diabetic. Forty weeks of hyper- glycemia induced significant vascular cell senescence in aortas of mice, as indicated by upregulation of expression of senes- cence-associated markers including p53, p21 and plasminogen activator inhibitor-1 （PAI-1）. However, SIRT1-Tg diabetic mice displayed dramatically decreased expression of p53, p21 and PAI-I compared with diabetic WT mice. Moreover, man- ganese superoxide dismutase expression （MnSOD） was significantly downregulated in the aortas of diabetic WT mice, but was preserved in diabetic SIRT1-Tg mice. Furthermore, expression of the oxidative stress adaptor p66Shc was significantly de- creased in aortas of SIRT1-Tg diabetic mice compared with WT diabetic mice. Overall, these findings suggest that SIRT 1-mediated inhibition of hyperglycemia-induced vascular cell senescence is mediated at least partly through the reduction of oxidative stress.
