ATM and Insulin resistance: ATM deficiency in mice causes insulin resistance, increased adiposity, atherosclerosis, and a variety of metabolic syndromes,421 while ATM activation is required in insulin-induced glucose transport in slow and fast muscle fibers utilizing glucose oxidation.422 Intriguingly, the repletion of NAD also attenuated the severity of AT-induced neuropathology, suggesting that accumulated DNA damage links to dysfunctional mitochondrial metabolism.423 ATM is the sensor for ROS in human fibroblasts, which also mediates mitochondrial ROS signaling and extends the life span of yeast.