Aerobic exercise and other healthy lifestyle factors that influence vascular aging

Abstract

Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote "resistance" against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging.

Keywords: arterial stiffness; endothelial dysfunction; inflammation; oxidative stress.

Copyright © 2014 The American Physiological Society.

Figures

Fig. 1.

Aging, arterial dysfunction, and cardiovascular disease (CVD) risk. Aging increases the risk of CVDs through the development of arterial dysfunction (vascular endothelial dysfunction and stiffening of large elastic arteries). As such, aerobic exercise and other evidence-based strategies that either prevent or reverse age-related arterial dysfunction are an important focus for biomedical research. [Modified from Ref. .]

Fig. 2.

Assessment of arterial stiffness and vascular endothelial function in human subjects and preclinical rodent models. Left: arterial stiffness assessed by measuring the time delay (Δt) between pressure waves at different arterial sites (aortic pulse wave velocity). Right: vascular endothelial function assessed by monitoring forearm blood flow (FBF) in response to ACh, measuring brachial artery dilation in response to increased blood flow [flow-mediated dilation (FMD)], or determining ACh-induced changes in arterial diameter in arteries isolated from experimental animals.

Fig. 3.

Structural mechanisms of aging and aerobic exercise on arterial stiffness. Aging induces arterial stiffness in part via structural changes to the arterial wall. Oxidative stress and inflammation involving excessive superoxide (O2·−) production and inflammatory cytokines mediate increases in collagen deposition, fragmentation of elastin, protein oxidation (nitrotyrosine), and formation of advanced glycation end products (AGEs). Aerobic exercise inhibits and/or reverses these age-related changes, resulting in suppression of arterial stiffening.

Fig. 4.

Mechanisms of aging and aerobic exercise on endothelial function. Aging leads to endothelial dysfunction mediated by vascular oxidative stress and inflammation. Excessive O2·− production, modulated by NADPH oxidase, SOD, uncoupling of endothelial nitric oxide (NO) synthase (eNOS), and other mechanisms (e.g., dysfunctional mitochondria), is a central mediator of these events. Excessive O2·− causes peroxynitrite (ONOO−) formation and protein oxidation (nitrotyrosine) as well as the activation of NF-κB and induction of inflammatory cytokines. [Modified from Ref. .] Aerobic exercise inhibits and/or reverses these age-related changes, resulting in enhanced endothelial function.

Fig. 5.

Aging, aerobic exercise, and adverse risk factors. Aging increases the risk of developing CVDs through stiffening of large elastic arteries and the development of vascular endothelial dysfunction. Aerobic exercise protects against arterial dysfunction not only by directly lowering traditional risk factors [e.g., low-density lipoprotein-cholesterol (LDL-C)] but also by inducing “resistance” against currently existing harmful levels of risk factors.

Fig. 6.

Aging, aerobic exercise, and other healthy lifestyle strategies. Aerobic exercise as well as other evidence-based complementary strategies (e.g., healthy dietary intake or nutraceuticals) that induce some of the protective effects of exercise by increasing NO bioavailability and antioxidant defenses [SOD, lowering O2·− production (e.g., by inhibiting NADPH oxidase), and reducing inflammation (i.e., activation of NF-κB and inflammatory cytokines)] serve to preserve vascular function with aging.