Why do blood vessels become stiffer with age?

As humans age, blood vessels naturally become stiffer and less elastic due to structural changes within their walls. This process is driven by two primary factors:12

• Collagen Cross-linking: There is a progressive thickening of vessel walls characterized by an increase in connective tissue. Specifically, the formation of cross-links within and between molecules of collagen increases over time, leading to greater rigidity in the tissue.123
• Elastin Fragmentation: Elastin is the protein responsible for the elasticity of blood vessel walls. With advancing age, the progressive fragmentation of these elastin molecules contributes to the loss of vessel flexibility.2

While arteriosclerosis—the hardening of arteries—is often associated with aging, these structural changes in connective tissue occur even in the absence of atherosclerosis, which involves the buildup of fatty plaques. This loss of elasticity increases resistance to blood flow, which can lead to higher blood pressure and force the heart to work harder to maintain circulation.1