Aerobic exercise training and vascular function with ageing in healthy men and women

Abstract

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in both men and women in developed societies. Age is the greatest risk factor for CVD due largely to adverse changes to arteries that include stiffening of the large elastic arteries (aortic and carotid arteries) and endothelial dysfunction. Vascular ageing is driven by oxidative stress, which reduces nitric oxide (NO) bioavailability and stimulates changes in the extracellular matrix. In women, reductions in circulating oestrogens with menopause interact with ageing processes to induce vascular dysfunction. Regular aerobic exercise is the most evidence-based strategy for reducing CVD risk with ageing in both men and women. Much of this cardiovascular-protective effect of aerobic exercise is likely due to its vascular health-enhancing influence. Large elastic artery stiffening with advancing age is attenuated in healthy adults engaged in aerobic exercise training, and aerobic exercise interventions improve arterial stiffness in previously sedentary middle-aged and older men and postmenopausal women. Regular aerobic exercise also enhances endothelial function with ageing in men (by reducing oxidative stress and preserving NO bioavailability), but not consistently in oestrogen-deficient postmenopausal women. In postmenopausal women, treatment with oestradiol appears to restore the ability of aerobic exercise to improve NO-mediated endothelial function by reducing oxidative stress. Several research gaps exist in our understanding of potential sex differences in the vascular adaptations to regular aerobic exercise. More information is needed on the factors that are responsible for sex differences, including the role of circulating oestrogens in transducing the aerobic exercise training 'stimulus'.

Keywords: arterial stiffness; endothelial function; estrogen; oxidative stress.

Figure 1.. Mechanisms of age-associated vascular dysfunction and subsequent cardiovascular diseases.

Aging in both men and women is associated with increased oxidative stress and inflammation, marked by increased superoxide (O^-₂) bioactivity and inflammatory mediators. Together, these processes induce vascular dysfunction, featuring (lower left) large elastic artery stiffening mediated by degradation of elastin fibers (purple), increased deposition of collagen fibers (brown), and greater crosslinking of elastin and collagen molecules by advanced glycation endproducts (dashed connecting lines); and (right) vascular endothelial dysfunction characterized by reduced nitric oxide (NO) bioavailability and endothelium-dependent dilation. These and other changes to arteries, in turn, increase the risk of developing clinical cardiovascular diseases.

Figure 2.. Aging, aerobic exercise and carotid artery compliance.

A: carotid artery compliance is reduced in both sedentary (Sed) and aerobic exercise trained (Ex) healthy older men and women compared to young controls; however, the age-related reduction in carotid compliance is attenuated by ~50% in Ex older adults. *P<0.05 vs. Young Sed, **P<0.05 vs Older Sed. B: carotid artery compliance increased by ~25–30% after 12 weeks of moderate-intensity aerobic exercise in previously sedentary healthy older men and estrogen-treated postmenopausal women. P<0.05 vs Before Ex. Data are from Tanaka et al. (Tanaka et al., 2000) and Moreau et al. (Moreau et al., 2003).

Figure 3.. Aging, aerobic exercise and endothelial function.

A: peak forearm blood flow (FBF) to acetylcholine (a measure of microvascular endothelial function) is reduced in healthy sedentary (Sed) older men (Older Before Ex) vs. Young Sed, older aerobic exercise trained (Older Ex) and older Sed men after aerobic exercise training (Older After Ex) (left). *P<0.05 vs. other groups. In women, peak FBF to acetylcholine is reduced in both Older Sed and Older Ex estrogen-deficient (postmenopausal) vs. Young Sed (premenopausal) (right). *P<0.05 vs. Young Sed. B: brachial artery flow-mediated dilation (FMD, a measure of macrovascular endothelial function) increased after 8 weeks of moderate-intensity aerobic exercise training in previously sedentary middle-aged/older men but not in estrogen-deficient postmenopausal women (left). Brachial artery FMD is greater in aerobic exercise-trained (Ex) compared to sedentary middle-aged/older men, but there is no difference in FMD between sedentary and Ex estrogen-deficient postmenopausal women (right). *P<0.05 vs Before Ex. Data are from DeSouza et al. (DeSouza et al., 2000), Santos-Parker et al. (Santos-Parker et al., 2017) and Pierce et al. (Pierce et al., 2011b).

Figure 4.. Sex differences in improvements in endothelial function to aerobic exercise training in middle-aged/older adults.

Brachial artery flow-mediated dilation (FMD) increased after 8–12 weeks of exercise training in healthy middle-aged/older (MA/O) men (far left) and postmenopausal women treated with estrogen-based hormone therapy (+HT, far right), but not in estrogen-deficient postmenopausal women (-HT) (middle left and middle right). Data are from Pierce et al. (Pierce et al., 2011b) and Moreau et al. (Moreau et al., 2013b). Reproduced from Moreau et al. (Moreau et al., 2013b).

Figure 5.. Mechanisms of aerobic exercise training on endothelial function in the absence and presence of estrogen in postmenopausal women.

In healthy estrogen-deficient postmenopausal women, aerobic exercise has no obvious effect on oxidative stress-suppression of vascular endothelium-dependent vasodilation. In contrast, estrogen treatment in postmenopausal women ameliorates the oxidative stress-related suppression of endothelial function with exercise training.

Figure 6.

Gaps in knowledge and future research directions.