CDKN1A and Hyperglycemia: Another study showed that streptozotocin-induced chronic hyperglycemia promotes vascular senescence in murine aortas, as evidenced by elevated PAI-1, p53, and p21 expression; SIRT1 overexpression ameliorated these effects and prevented the downregulation of manganese superoxide dismutase (MnSOD) induced by hyperglycemia [57].