Aortic stiffening, assessed as pulse-wave velocity (PWV), increases with age and is an important antecedent to, and independent predictor of, cardiovascular diseases (CVD) and other clinical disorders of aging. Aerobic exercise promotes lower levels of aortic stiffness in older adults, but the underlying mechanisms are incompletely understood, largely due to inherent challenges of mechanistic studies of large elastic arteries in humans. Voluntary wheel running (VWR) is distinct among experimental animal exercise paradigms in that it allows investigation of the physiologic effects of aerobic training without potential confounding influences of aversive molecular signaling related to forced exercise. In this study, we investigated whether VWR in mice may be a suitable model for mechanistic studies (i.e., "reverse translation") of the beneficial effects of exercise on arterial stiffness in humans. We found that 10 weeks of VWR in old mice (~ 28 months) reversed age-related elevations in aortic PWV assessed in vivo (Old VWR: 369 ± 19 vs. old sedentary: 439 ± 20 cm/s, P < 0.05). The de-stiffening effects of VWR were accompanied by normalization of age-related increases in ex vivo mechanical stiffness of aortic segments and aortic accumulation of collagen-I and advanced glycation end products, as well as lower levels of aortic superoxide and nitrotyrosine. Our results suggest that late-life VWR in mice recapitulates the aortic de-stiffening effects of exercise in humans and indicates important mechanistic roles for decreased oxidative stress and extracellular matrix remodeling. Therefore, VWR is a suitable model for further study of the mechanisms underlying beneficial effects of exercise on arterial stiffness.

中文翻译：

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晚年自愿轮跑逆转小鼠与年龄相关的主动脉僵硬：一种用于研究运动介导的动脉去硬化机制的转化模型。

以脉搏波速度 (PWV) 评估的主动脉硬化随着年龄的增长而增加，并且是心血管疾病 (CVD) 和其他衰老临床疾病的重要前因和独立预测因子。有氧运动可降低老年人的主动脉僵硬度水平，但其潜在机制尚不完全清楚，这主要是由于人类大弹性动脉的机械研究存在固有挑战。自愿轮跑 (VWR) 在实验动物运动范例中是不同的，因为它允许研究有氧训练的生理效应，而不会受到与强迫运动相关的厌恶分子信号的潜在混淆影响。在这项研究中，我们调查了小鼠的 VWR 是否可能是机械研究的合适模型（即“反向翻译” ) 运动对人体动脉硬化的有益影响。我们发现老年小鼠（~ 28 个月）的 10 周 VWR 逆转了体内评估的主动脉 PWV 中与年龄相关的升高（旧 VWR：369 ± 19 vs. 久坐不动：439 ± 20 cm/s，P < 0.05）。VWR 的去硬化作用伴随着与年龄相关的主动脉节段体外机械刚度增加和胶原蛋白-I 和晚期糖基化终产物的主动脉积累以及主动脉超氧化物和硝基酪氨酸水平降低的正常化。我们的研究结果表明，小鼠晚年 VWR 概括了运动对人类主动脉的去硬化作用，并表明了减少氧化应激和细胞外基质重塑的重要机制作用。所以，