The Complexities of Vascular Aging

We are as old as our arteries, as the saying goes. The aging of the vasculature impacts all of the tissues in the body, and there are many distinct mechanisms by which this happens. The loss of capillary density reduces the supply of oxygen and nutrients to energy-hungry tissues such as muscles and the brain. The stiffening of vessels leads to hypertension and pressure damage to delicate tissues throughout the body. The leakage of the blood-brain barrier allows unwanted molecules and cells to provoke chronic inflammation in the brain. The fatty deposits of atherosclerosis narrow and weaken blood vessels, further reducing blood flow and allowing harmful rupture and blockage in vessels large and small.

A broad range of underlying mechanisms of aging contribute to the vascular dysfunction in old people. Effective repair and rejuvenation will not be achieved by just one therapy, or one class of therapies. Chronic inflammation, disruptive of vascular smooth muscle activity, must be addressed, such as via targeted destruction of senescent cells. The cross-linking that stiffens blood vessel walls must be reversed. The localized deposits of cholesterol characteristic of atherosclerosis must be cleared. And so on and so forth. Vascular aging is one of the better examples to clearly demonstrate that the manifestations of aging are the sum of many underlying processes. Incremental gains will be made by each new treatment that targets one of those processes, but all must be dealt with in order to achieve complete rejuvenation.

Aging of Vascular System Is a Complex Process: The Cornerstone Mechanisms

Changes in arterial structure and function accompanying aging lead to an increased risk of cardiovascular diseases (CVD). Thus, understanding the mechanisms by which age affects the vascular system can help to avoid altogether or to reduce the high risk of developing cardiovascular diseases in elderly people. Several new (preliminary) clinical studies have found that the most important vascular changes occur with aging and described 2 key traits: (1) generalized endothelial dysfunction and (2) stiffness of the central artery. As for generalized endothelial dysfunction, vascular aging alters the endothelium function and the cells that cover the lumen of blood vessels. Endothelial dysfunction includes a decrease in vasodilatory and antithrombotic properties, with an elevation in oxidative stress and inflammatory cytokines, which favor atherogenesis and thrombosis and predispose to cardiovascular diseases. Both human and experimental studies have proven a reduction in the bioavailability of nitric oxide (NO), a major mediator of vasorelaxation and antiatherogenic processes that are the foundation of age-related endothelial dysfunction.

With aging, the elasticity of arteries, especially the aorta, decreases. This leads to arterial stiffness, which is, at least in part, the result of gradual fragmentation and loss of elastin fibers and accumulation of stiffer collagen fibers. The risk of hypertension and the range of various disorders are tightly linked to increased arterial stiffness. Vascular calcification is specific for aging and vascular stiffness. The development of calcification is accelerated in patients with hypertension, diabetes mellitus, and other disorders. However, an exact mechanism linking calcification with aging is still unclear.

During the process of aging, a shift towards the pro-inflammatory phenotype with elevated expression of inflammatory cytokines, adhesion molecules, and chemokines from endothelial cells (ECs) has been observed. These pro-inflammatory cytokines include interleukin (IL)-6, IL-1β, cellular adhesion molecules, tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1. Prolonged exposure to TNF-α leads to early aging of the endothelium, which can be avoided by suppressing the activation of NF-KB. This fact gives rise to the hypothesis that inflammation leads to premature aging of the endothelium. Thus, human aging is a chronic, systemic and low-grade pro-inflammatory condition, and this phenomenon has been defined as "inflammaging".

All body systems age, lose their performance, and structural disorders accumulate. The cardiovascular system is no exception. And it is cardiovascular diseases that occupy a leading position as a cause of death, especially among the elderly. The aging of the cardiovascular system is well described from a mechanical point of view. Moreover, it is known that at the cellular level, a huge number of mechanisms are involved in this process, from mitochondrial dysfunction to inflammation. It is on these mechanisms, as well as the potential for taking control of the aging of the cardiovascular system, that we focused on in this review.