Lifelong voluntary aerobic exercise prevents age‐ and Western diet‐ induced vascular dysfunction, mitochondrial oxidative stress and inflammation in mice

Abstract

Key points The results of the present study establish the temporal pattern of age‐related vascular dysfunction across the adult lifespan in sedentary mice consuming a non‐Western diet, and the underlying mechanisms The results demonstrate that consuming a Western diet accelerates and exacerbates vascular ageing across the lifespan in sedentary mice They also show that lifelong voluntary aerobic exercise has remarkable protective effects on vascular function throughout the lifespan, in the setting of ageing alone, as well as ageing compounded by Western diet consumption Overall, the results indicate that amelioration of mitochondrial oxidative stress and inflammation are key mechanisms underlying the voluntary aerobic exercise‐associated preservation of vascular function across the lifespan in both the presence and absence of a Western dietary pattern Abstract Advancing age is the major risk factor for cardiovascular diseases, driven largely by vascular endothelial dysfunction (impaired endothelium‐dependent dilatation, EDD) and aortic stiffening (increased aortic pulse wave velocity, aPWV). In humans, vascular ageing occurs in the presence of differences in diet and physical activity, but the interactive effects of these factors are unknown. We assessed carotid artery EDD and aPWV across the lifespan in mice consuming standard (normal) low‐fat chow (NC) or a high‐fat/high‐sucrose Western diet (WD) in the absence (sedentary, SED) or presence (voluntary wheel running, VWR) of aerobic exercise. Ageing impaired nitric oxide‐mediated EDD (peak EDD 88 ± 12% 6 months P = 0.003 vs. 59 ± 9% 27 months NC‐SED), which was accelerated by WD (60 ± 18% 6 months WD‐SED). In NC mice, aPWV increased 32% with age (423 ± 13 cm/s at 24 months P < 0.001 vs. 321 ± 12 cm/s at 6 months) and absolute values were an additional ∼10% higher at any age in WD mice (P = 0.042 vs. NC‐SED). Increases in aPWV with age in NC and WD mice were associated with 30–65% increases in aortic intrinsic wall stiffness (6 vs. 19–27 months, P = 0.007). Lifelong aerobic exercise prevented age‐ and WD‐related vascular dysfunction across the lifespan, and this protection appeared to be mediated by mitigation of vascular mitochondrial oxidative stress and inflammation. Our results depict the temporal impairment of vascular function over the lifespan in mice, acceleration and exacerbation of that dysfunction with WD consumption, the remarkable protective effects of voluntary aerobic exercise, and the underlying mechanisms.

Vitamin D Deficiency and Risk of Metabolic Syndrome in Aging Men

“…Moreover, environmental factors as air pollution [ 19 20 21 ], physical activity [ 25 26 ], and diet [ 27 28 ] greatly influences senescence biomarkers and MetS development.…”

“…Furthermore, biological pathways leading to senescence are influenced by physical activity [ 25 26 82 ] and nutritional intake [ 27 28 51 ]. Also air pollution has been associated with accelerated senescence, lower 25(OH)D levels, and increased risk of MeTS [ 19 83 ].…”

Chronic aerobic exercise: targeting two birds with one stone

“…In this issue of The Journal of Physiology , Gioscia‐Ryan et al . (2021) report an elegant study aimed at elucidating the complex interaction of age, diet, and exercise on EDD and arterial stiffness across the lifespan of mice. Young male C57BL/6 mice were divided into groups consuming either normal chow or a Western diet (WD) over their lifespan.…”

“…Gioscia‐Ryan et al . (2021) demonstrate that the combination of ageing and lifelong WD exacerbates endothelial dysfunction and large artery stiffening, both of which are accompanied by increased oxidative stress and inflammation. However, while oxidative stress and inflammation track closely with declines in EDD, the emergence of increased arterial stiffness does not correspond to the observed elevations in markers of either oxidative stress or inflammation.…”

“…In conclusion, this study by Gioscia‐Ryan et al . (2021) builds upon existing literature by providing critical insight into the role of mitochondrial oxidative stress and inflammation in the vascular ageing phenotype, as well as its exacerbation by WD and prevention by exercise across the lifespan. The findings from this study are in agreement with, and enhance the significance of, previous short‐term intervention studies that suggested consumption of a WD accelerates the development of the vascular ageing phenotype through increases in oxidative stress and inflammation.…”