Dietary Nitrate and Muscle Power with Aging

项目摘要 肌肉力量、速度和力量随着年龄的增长而下降，这些变化高度预测残疾， 机构化和老年人的死亡率。一个可能导致肌肉损伤的因素是 与年龄相关的功能是一氧化氮（NO）产生的年龄相关的减少。NO是一种重要的细胞信号 分子，在许多组织中，包括肌肉，其中除其他作用外，它影响收缩特性。与 然而，随着年龄的增长，NO合酶活性下降，因此肌肉中的NO生物利用度下降， 证据，例如，通过其“下游”代谢物浓度的下降，即，亚硝酸盐（NO2-）和硝酸盐 （NO3-）。因此，我们假设，膳食补充NO3-，这可以是非酶促的， 减少形成NO，将增加老年人的肌肉速度和力量。为了验证这些假设， 随机、安慰剂对照、交叉设计将用于测试20名65-79岁的男性和女性 摄入浓缩甜菜根汁（BRJ）补充剂，其含有或耗尽11.2 mmol的NO3- (i.e., BRJ w/ NO3-或BRJ w/o NO3-）。急性（即，Id）BRJ w/或w/o NO3-对肌肉速度的影响，和 使用等速测力法测定功率。后一种测试将在慢性（即，14 d） 饮食补充BRJ w/或w/o NO3-，在此期间，将使用 将通过问卷调查评估日常生活中的加速度测量和感知疲劳和身体功能。 无论是急性还是慢性，血浆和肌肉NO3-和NO2-浓度都将使用高浓度 高效液相色谱法，呼吸NO水平（全身NO产生的生物标志物）将被 使用电化学分析仪测量，并通过ELISA定量肌肉环GMP浓度 因此，任何饮食NO3-诱导的肌肉功能变化都可以与这些参数机械地联系起来。 这项概念验证研究将导致更广泛的，随机的，多中心的试验研究，将检查更广泛的 这种饮食疗法在老年人中的适用性。这项研究也将导致更深入的研究 来自膳食NO3-的NO在老年人中的作用机制。对公众健康的潜在影响 发现饮食中的NO3-显著提高老年人的肌肉速度和力量是巨大的。

PROJECT SUMMARY Muscular strength, speed, and power decrease with aging, with such changes being highly predictive of disability, institutionalization, and mortality in the elderly. One factor potentially contributing to this impairment of muscle function with age is an age-related decrease in nitric oxide (NO) production. NO is a key cellular signaling molecule in many tissues, including muscle, where among other effects it influences contractile properties. With aging, however, there is a drop in NO synthase activity and hence in NO bioavailability within muscle, as evidenced, e.g., by a decline in the concentration of its “downstream” metabolites, i.e., nitrite (NO2-) and nitrate (NO3-). We therefore hypothesize that dietary supplementation with NO3-, which can be non-enzymatically reduced to form NO, will increase muscle speed and power in older persons. To test this hypotheses, a randomized, placebo-controlled, crossover design will be used to test 20 men and women 65-79 y of age ingesting a concentrated beetroot juice (BRJ) supplement either containing or depleted of 11.2 mmol of NO3- (i.e., BRJ w/ NO3- or BRJ w/o NO3-). The acute (i.e., 1 d) effects of BRJ w/ or w/o NO3- on muscular speed and power will be determined using isokinetic dynamometry. The latter tests will be repeated after chronic (i.e., 14 d) dietary supplementation with BRJ w/ or w/o NO3-, during which time physical activity will be measured using accelerometry and perceived fatigue and physical function during daily life will be assessed via questionnaire. Both acutely and chronically, plasma and muscle NO3- and NO2- concentrations will be determined using high performance liquid chromatography, breath NO levels (a biomarker for whole-body NO production) will be measured using an electrochemical analyzer, and muscle cyclic GMP concentrations will be quantified via ELISA so that any dietary-NO3--induced changes in muscle function can be mechanistically-linked to these parameters. This proof-of-concept study will lead to broader, randomized, multi-center trial studies that will examine the wider applicability of this dietary treatment in older persons. This study will also lead to deeper studies into the mechanisms of action of NO derived from dietary NO3- in older individuals. The potential impact on public health of finding that dietary NO3- significantly enhances muscle speed and power in older individuals is enormous.