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Dietary Nitrate and Muscle Power with Aging

膳食硝酸盐与衰老过程中的肌肉力量

基本信息

批准号：
9764237
负责人：
ANDREW R COGGAN
金额：
$ 19.69万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9764237
关键词：
Accelerometer Activities of Daily Living Acute Address Age Aging Anaerobic Bacteria Arginine Biological Availability Biological Markers Biopsy Carcinogens Chronic Consumption Crossover Design Cyclic GMP Data Development Diet Dietary Supplementation Dose Double-Blind Method Drops Elderly Enzyme-Linked Immunosorbent Assay Extensor Fatigue Heart failure High Pressure Liquid Chromatography Impairment Individual Ingestion Institutionalization Intake Isoenzymes Isotonic Exercise Juice Knee Lead Life Link Measures Mediating Metabolic Metabolism Multicenter Trials Muscle Muscle function NADP NOS1 gene Nitrates Nitric Oxide Nitric Oxide Synthase Nitric Oxide Synthase Type I Nitrites Oral cavity Pathway interactions Patients Performance Physical Function Physical activity Placebos Plasma Play Production Property Public Health Publishing Questionnaires Randomized Research Project Grants Rest Role Signal Transduction Signaling Molecule Skeletal Muscle Soluble Guanylate Cyclase Source Speed Supplementation System Testing Time Tissues Woman age related age-related muscle loss base deoxyhemoglobin dietary nitrate disability interstitial men middle age mortality older men older women pleiotropism

项目摘要

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.

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，有证据表明，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。