Dietary Nitrate and Muscle Power with Aging

项目总结

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.