Relating to NOX-mitochondria crosstalk, aging-associated activation of NOX enzymes enhances superoxide (O2•−) production, which in turn triggers mitochondrial ROS release, further amplifying oxidative stress.76 The activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase by mitochondrial ROS promotes pro-inflammatory gene expression and endothelial dysfunction.12 Dysregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling impairs antioxidant responses, resulting in unchecked ROS accumulation and endothelial nitric oxide synthase uncoupling. Here, NFE2L2 is linked to endothelial dysfunction.