All of these metabolic pathways activated by chronic hyperglycemia contribute to marked oxidative stress, which induces double-strand breaks (DSBs) in the DNA and subsequently leads to the activation of ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2), which activate the p53 signaling pathway and induce senescence [175]. Here, ATM is linked to Hyperglycemia.