Blood vessels stiffen with age, and this appears to be the primary cause of age-related hypertension, or raised blood pressure. That raised blood pressure in turn damages delicate tissues, increasing the pace at which ruptures occur in capillaries throughout the body. In the brain this causes many tiny, silent strokes over the years, adding up to create cognitive decline. Eventually hypertension combines with the corrosive effect of atherosclerosis on blood vessel walls to cause some form of fatal structural failure in a major blood vessel.
The causes of stiffening of blood vessels include cross-linking that disrupts the physical properties of the extracellular matrix, the related loss of elastin in the matrix, and dysfunction in the vascular smooth muscle cells responsible for constriction and dilation of blood vessels. That cellular dysfunction has a whole set of deeper causes, not all of which are well understood at this time. The chronic inflammation and harmful signaling generated by senescent cells seems to be involved, but it isn't the whole story by any means.
Aging is associated with a progressive decline in vasoconstrictor responses in central and peripheral arteries. The mechanism responsible for the age-related decrease in vasoconstrictor function has not been fully elucidated but may involve an impaired ability of vascular smooth muscle (VSM) cells to develop contractile tension. This hypothesis is supported by evidence indicating that myogenic constrictor responses in skeletal muscle arterioles declined with age. In addition, agonist-induced vasoconstrictor responses to norepinephrine (NE), phenylephrine (PE), and angiotensin II (Ang II) were impaired in endothelium intact skeletal muscle feed arteries (SFA) from old rats when compared to young rats.
Arterial aging results in progressive changes in the mechanical properties of the vessel wall leading to increased wall stiffness and an impaired ability of aged blood vessels to control local blood flow and pressure. At the microscopic level, this translates to decreased responsiveness of VSM and endothelial cells to mechanical stimuli. This impairment, in turn, induces compensatory hypertrophic or hyperplastic remodeling of aged arteries. The discrete VSM cell mechanical properties and their ability to adapt to external mechanical signals (e.g., blood pressure and flow) directly contribute to maintaining vessel tone.
Vascular smooth muscle cells play an integral role in regulating matrix deposition and vessel wall contractility via interaction between the actomyosin contractile unit and adhesion structures formed at the cell membrane that mechanically link the cell to the matrix. The actin cytoskeleton is responsible for maintaining cell shape and provides the platform for the distribution of mechanical signals throughout the cell. This mechanical load-bearing cell-matrix interaction is key to maintaining the contractile state of resistance arteries. Most studies to date on arterial aging have focused on the role played by endothelial dysfunction or changes in the extracellular matrix, and less on the contribution of VSM cells that control vessel tone. However, there is emerging interest in the role VSM cells play in regulating vessel wall stiffness.