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.

项目摘要随着衰老的肌肉力量，速度和功率降低，这种变化高度预测了残疾，可能导致这种肌肉损害的一个因素年龄的功能是一氧化氮（NO）产生与年龄有关的降低。否是关键的蜂窝信号传导包括肌肉在内的许多组织中的分子，其中包括其他影响收缩特性。和然而，衰老的无合酶活性下降，因此肌肉内无生物利用度，如例如，通过其“下游”代谢物的浓度下降，即亚硝酸盐（NO2-）和硝酸盐的浓度下降。（no3-）。因此，我们假设用No3-补充饮食，这可能是非酶的减少形成不，会增加老年人的肌肉速度和力量。为了检验这个假设，随机，安慰剂对照，跨界设计将用于测试20名男性和女性65-79岁的年龄摄入含有或耗尽11.2 mmol的NO3--的浓缩甜菜根汁（BRJ）（即，brj w/ no3-或brj w/ o no3-）。 brj w/或w/ o no3-对肌肉速度和功率将使用Isokinetic Dynemetry确定。慢性后将重复以后的测试（即14 d）补充饮食，用brj w/或w/ o no3--使用日常生活中的加速度计和感知的疲劳和身体机能将通过问卷进行评估。急性和慢性，血浆和肌肉NO3-和NO2浓度都将使用高确定性能液相色谱法，呼吸没有水平（全身无生产的生物标志物）是使用电化学分析仪和肌肉循环GMP浓度测量，将通过ELISA进行量化因此，任何饮食中诱导的肌肉功能变化都可以机械地连接到这些参数。这项概念验证研究将导致更广泛，随机，多中心的试验研究，该研究将检查野外这种饮食治疗在老年人中的适用性。这项研究还将导致对老年人源自饮食的NO3-源自饮食的作用机制。对公共卫生的潜在影响发现饮食NO3显着提高了老年人的肌肉速度和力量是巨大的。