Aerobic exercise is the most well-known and effective intervention to prevent and treat cardiovascular diseases (CVD) with aging. Aerobic exercise suppresses excess amounts of nuclear factor-κB (NF-κB)-mediated inflammation and oxidative stress originating from mitochondrial- and NADPH oxidase (NOX4)-derived reactive oxygen species (ROS). Aerobic exercise may also favorably modulate the adverse effects induced by fundamental aging mechanisms, i.e., mitochondrial dysfunction, deregulated nutrient sensing, cellular senescence and circulating factors, to ultimately improve arterial function.