The Implications of Aging on Vascular Health

Abstract

Vascular aging encompasses structural and functional changes in the vasculature, significantly contributing to cardiovascular diseases, which are the leading cause of death globally. The incidence and prevalence of these diseases increase with age, with most morbidity and mortality attributed to myocardial infarction and stroke. Diagnosing and intervening in vascular aging while understanding the mechanisms behind age-induced vascular phenotypic and pathophysiological alterations offers the potential for delaying and preventing cardiovascular mortality in an aging population. This review delves into various aspects of vascular aging by examining age-related changes in arterial health at the cellular level, including endothelial dysfunction, cellular senescence, and vascular smooth muscle cell transdifferentiation, as well as at the structural level, including arterial stiffness and changes in wall thickness and diameter. We also explore aging-related changes in perivascular adipose tissue deposition, arterial collateralization, and calcification, providing insights into the physiological and pathological implications. Overall, aging induces phenotypic changes that augment the vascular system's susceptibility to disease, even in the absence of traditional risk factors, such as hypertension, diabetes, obesity, and smoking. Overall, age-related modifications in cellular phenotype and molecular homeostasis increase the vulnerability of the arterial vasculature to structural and functional alterations, thereby accelerating cardiovascular risk. Increasing our understanding of these modifications is crucial for success in delaying or preventing cardiovascular diseases. Non-invasive techniques, such as measuring carotid intima-media thickness, pulse wave velocity, and flow-mediated dilation, as well as detecting vascular calcifications, can be used for the early detection of vascular aging. Targeting specific pathological mechanisms, such as cellular senescence and enhancing angiogenesis, holds promise for innovative therapeutic approaches.

Keywords: aging; and cardiovascular diseases; arterial stiffness; calcification; cellular senescence; rarefaction; vascular dysfunction.

Figure 1

The aging-associated structural alterations in large arteries. Unlike younger arteries, the aged vasculature undergoes significant changes characterized by elastin degradation and collagen accumulation, leading to increased stiffness, thickness, and decreased elasticity. Age-related intimal thickening is consistently observed across all large arteries, while the carotid artery is notable for thickening in all the intima, media, and adventitia layers. There is a noticeable expansion in the lumen diameter and evident fat deposition on the adventitia. Calcification also occurs in both the intima and medial layers of large arteries. At the cellular level, changes associated with the hypertrophy, senescence, and apoptosis of VSMCs and endothelial cells are evident. VSMCs migrate from the media to the intima and exhibit dysfunctional characteristics. Endothelial dysfunction is also apparent, which significantly reduces vasodilation and neo-vascularization in the elderly. Factors such as inflammation, diabetes, smoking, obesity, hypertension, oxidative stress, and unhealthy lifestyle choices can further exacerbate vascular aging.