Dietary Nitrate and Muscle Power with Aging

项目总结 肌肉力量、速度和力量随着年龄的增长而下降，这种变化高度预示着残疾， 制度化和老年人的死亡率。可能导致肌肉损伤的一个因素 功能随年龄增长是一种与年龄相关的一氧化氮(NO)生成减少。一氧化氮是一种关键的细胞信号 在许多组织中，包括肌肉中的分子，除了其他作用外，它还影响收缩特性。使用 然而，随着年龄的增长，一氧化氮合酶活性会下降，因此肌肉中的生物利用度也会下降，因为 例如，其“下游”代谢物，即亚硝酸盐(NO2-)和硝酸盐的浓度下降 (第三名)。因此，我们假设饮食中添加NO3-，它可以是非酶类的 减少到NO形式，将增加老年人的肌肉速度和力量。为了检验这一假设，一个 随机、安慰剂对照、交叉设计将用于测试20名年龄在65-79岁的男性和女性 摄入浓缩甜菜根汁(BRJ)补充剂，含有或消耗11.2毫摩尔的硝酸根- (即，带NO3-的BRJ或不带NO3-的BRJ)。BRJ无或无NO_3-对肌肉速度的急性(即1天)影响 功率将用等速测力法测定。后一项测试将在慢性(即14天)后重复进行 饮食补充BRJ w/或w/o NO_3-，在此期间，体力活动将使用 日常生活中的加速计和感觉疲劳及身体机能将通过问卷调查进行评估。 无论是急性的还是慢性的，血浆和肌肉中的NO3-和NO2-浓度都将使用高 高效液相色谱、呼吸NO水平(全身NO产生的生物标志物)将 使用电化学分析仪测量，肌肉循环GMP浓度将通过酶联免疫吸附试验定量 因此，饮食中硝酸盐引起的肌肉功能的任何变化都可以从机械上与这些参数联系起来。 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，这些研究将检查更广泛的 这种饮食治疗在老年人中的适用性。这项研究也将导致对 老年人饮食中NO的作用机制。对公众健康的潜在影响 发现饮食中的N3-显著提高老年人的肌肉速度和力量的可能性是巨大的。

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.