Bioenergetics and fatigability in older individuals

老年人的生物能和疲劳性

基本信息

批准号：
8712312
负责人：
ROBERT G WEISS
金额：
$ 15.75万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-15 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8712312
关键词：
ATP Hydrolysis ATP Synthesis Pathway Accounting Activities of Daily Living Adenosine Diphosphate Age Aging Algorithms Animal Model Biochemical Bioenergetics Biological Markers Blood flow Cardiac Cardiovascular system Cessation of life Clinical Collaborations Coupled Creatine Creatine Kinase Data Effectiveness Elderly Energy Metabolism Exercise Fatigue Future Human In Vitro Individual Inflammatory Intervention Intervention Studies Laboratories Lipids MM form creatine kinase Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measures Metabolic Metabolism Methods Muscle Muscle Fatigue Muscle Fibers Muscle function Neurologic Observational Study Older Population Performance Perfusion Phosphocreatine Physiological Play Population Prevalence Production Protocols documentation Reaction Recovery Reproducibility Research Personnel Rest Role Skeletal Muscle Staging Stress Stress Tests Symptoms Techniques Testing Time Work Workload base clinically relevant combat fatigue deprivation disability experience fitness frailty improved in vivo indexing inorganic phosphate insight mortality muscle form novel prognostic public health relevance response therapy design tool

项目摘要

DESCRIPTION (provided by applicant): Fatigue is a common and important symptom among the elderly that is associated with a several-fold increase in disability and mortality. Because ATP is absolutely required to fuel normal muscle contractile function and fatigue has been conceptualized as a state of energy deficiency, an approach to characterizing bioenergetics in older subjects with fatigue is both logical and compelling. We propose here a muscle bioenergetics fatigability test that employs standardized, graded exercise conducted to performance fatigue coupled with 31P magnetic resonance spectroscopy so as to relate the level, duration and intensity of activity with fatigue symptoms and with exercising skeletal muscle bioenergetics, including repeated measures of high-energy phosphate levels, inorganic phosphate accumulation, and intracellular pH. In addition, potential mechanisms responsible for changes in metabolite levels will be studied by measuring maximal oxidative capacity, intracellular lipid content, and by magnetization transfer techniques, developed in our laboratory, to determine the rate of ATP production via creatine kinase, the primary muscle energy reserve reaction. These parameters will also be related to global indices of fatigue and cardiovascular fitness, to systemic inflammatory biomarkers, and to local factors including muscle mass and blood flow. In collaboration with the NIA BLSA populations we propose to test the hypotheses that 1) at similar workloads, muscle high-energy phosphates are reduced and Pi increased in older subjects with high, as compared to those with low, fatigability, that 2) performance fatigue occurs at the same energetic threshold but at lower workload/activity in those with high fatigability, and that 3) some responsible mechanisms for performance fatigue-related changes in high energy phosphate levels can be identified. This novel and potentially transformative approach will offer for the first time a means to objectively identify increased muscle fatigabilit, to define the role of reduced muscle energy metabolism in aging-associated fatigability, to explore responsible mechanisms, and to provide a standardized method to assess the impact of future interventions on the bioenergetic profile in older individuals with performance fatigue.

描述（由申请人提供）：疲劳是老年人中常见且重要的症状，与残疾和死亡率增加几倍有关。由于ATP绝对需要加强正常的肌肉收缩功能，并且疲劳已被概念化为一种能量缺乏状态，因此表征疲劳的老年受试者的生物能学的一种方法既合乎逻辑又具有吸引力。 We propose here a muscle bioenergetics fatigability test that employs standardized, graded exercise conducted to performance fatigue coupled with 31P magnetic resonance spectroscopy so as to relate the level, duration and intensity of activity with fatigue symptoms and with exercising skeletal muscle bioenergetics, including repeated measures of high-energy phosphate levels, inorganic phosphate accumulation, and intracellular pH.此外，将通过测量最大氧化能力，细胞内脂质含量以及通过在我们的实验室中开发的磁化转移技术来研究负责代谢物水平变化的潜在机制。为了通过肌酸激酶确定ATP产生的速率，这是主要的肌肉能量储备反应。这些参数也将与全球疲劳和心血管健身，全身性炎症生物标志物以及包括肌肉质量和血流在内的局部因素有关。通过与NIA BLSA人群的合作，我们建议测试假设1）在类似工作量下，肌肉高能量磷酸盐减少，并且在较高的较低，疲劳性低的年龄较大的受试者中，PI增加了PI，与较低的性能疲劳相比，2）在同一能量的效果上发生了较低的工作，并且在高度疲劳的情况下会发生较低的效果，并且在高度效果上发生了一些激烈的效果，并且在高度效果上，这是一定的，并且在3个效果上是在高度效果的情况下，并且在3个）中进行了3），这是在高度效果上，并且在3个）上进行了3）。可以鉴定出高能量磷酸盐水平。这种新颖的和潜在的变革性方法将首次提供一种方法来客观地识别肌肉疲劳的增加，以定义降低肌肉能量代谢在与衰老相关的疲劳性中的作用，以探索负责任的机制，并提供一种标准化的方法，以评估未来干预措施对生物监护症患者的影响。