![]() The following review discusses what is currently known regarding the biology of vascular aging, clinical manifestations of age-associated vascular disease with a focus on calcification, the impact of genetic risk on vascular aging, and the environmental and molecular factors that may influence vascular aging and promote longevity ( Figure).Ĭlinical Manifestations of Age-Associated Cardiovascular CalcificationĪrterial stiffening and calcification are characteristics of vascular aging, serve as important predictors of cardiovascular morbidity and mortality, and are exacerbated by cardiovascular disease risk factors and metabolic syndromes. ![]() Improving our understanding of vascular aging and its role in cardiovascular disease progression, morbidity, and mortality is essential. Studies of human longevity are also challenging due to the costly and time-consuming nature of studying an individual human over a lifespan, and long-lived individuals may have different genetic longevity variants and protein signatures. Studies, such as the PESA (Progression and Early Detection of Subclinical Atherosclerosis) 1 and the Asklepios Study, 2 were designed to circumnavigate these challenges to study the interactions of age and inflammation with cardiovascular hemodynamics and development of atherosclerosis. Although studies of aging exist, they are prone to survival bias in that only individuals who survived until older age can be studied if not enrolled earlier in life. Second, there is likely a synergistic effect of both the duration and number of cardiovascular risk factors that make it challenging to fully adjust for such variables. First, vascular aging is often accompanied by one or more cardiovascular disease risk factors. Isolating vascular aging as an independent biological variable is challenging for several reasons. The importance of understanding the interplay between vascular biology and aging, independent of traditional risk factors, is of utmost importance. However, with advancing age, even individuals without traditional risk factors gradually develop vascular pathology including arterial fibrosis, stiffness, and calcification, increasing the risk of serious cardiovascular events. Genetic risk, likely compounded by epigenetic modifications, environmental factors, including diabetes mellitus and chronic kidney disease, and the plasticity of vascular smooth muscle cells to acquire an osteogenic phenotype are major determinants of age-associated vascular calcification.Īrterial smooth muscle cell phenotypic switching contributes significantly to vascular aging-manifested as abnormal conduit vessel physiology and mechanical integrity due to arteriosclerotic calcification, fibrosis, matrix remodeling, and impaired contractile functions.Ĭardiovascular disease is the leading cause of death worldwide and increases with age, in large part due to the cumulative effects of risk factors, such as hypertension, hyperlipidemia, diabetes, tobacco use, and sedentary behavior. The pathogenesis underlying the development of vascular aging, and vascular calcification with aging, in particular, is still not fully understood. This article summarizes current knowledge of concepts and mechanisms of age-associated vascular disease, with an emphasis on vascular calcification. Understanding the molecular mechanisms underlying genetic and modifiable risk factors in regulating age-associated vascular pathology may inspire strategies to promote healthy vascular aging. Accumulating data suggests that genetic risk, likely compounded by epigenetic modifications, environmental factors, including diabetes and chronic kidney disease, and the plasticity of vascular smooth muscle cells to acquire an osteogenic phenotype are major determinants of age-associated vascular calcification. ![]() Vascular pathology stems from a combination of genetic risk, environmental factors, and the biologic changes associated with aging.
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