Combined with prior observations on the requirement of KLF4 for mechanotransduction pathways in endothelial cells, we propose that age-associated increases in disturbed blood flow lead to lowered levels of KLF4 in blood vessels to promote endothelial dysfunction and, over time, contribute to the increased risk of atherosclerosis and other vessel-related pathology seen in aged individuals38, 39. This evidence concerns the gene KLF4 and endothelial dysfunction.