Increasing collagen-to-elastin ratios in vessel walls, altered cytoskeletal components in vascular smooth muscle cells (i.e., vascular smooth muscle cell stiffness), remodeling of the extracellular matrix and cell–matrix crosstalk, endothelial dysfunction, and vascular calcium deposition are some of the proposed mechanisms of age-associated vascular stiffening based on both animal and human studies. The gene discussed is ELN; the disease is endothelial dysfunction.