SIRT3 and Hyperglycemia: The dysregulated NAD+/NADH ratio, together with the absence of SIRT3, may cause cell cycle and mitosis arrest, and mediate metabolic changes in aging by activating AMPK to initiate senescence via the classical p53 pathway.263 Under hyperglycemic conditions, overexpression of mitochondrial uncoupling protein 2 induced the up-regulation of NAD+ and SIRT3, and alleviated senescence caused by hyperglycemia.264