Noninvasive assessment of microvascular function in aging

衰老过程中微血管功能的无创评估

• 批准号: 8284589
• 负责人: Jill M Slade
• 金额: $ 23.03万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8284589
• 关键词: ATP Synthesis Pathway; Adult; Aerobic Exercise; Age; Aging; Arteries; Automobile Driving; Bioenergetics; Blood; Blood Vessels; Blood Volume; Blood flow; Cell Respiration; Clinical; Consensus; Data; Detection; Diabetes Mellitus; Disease; Disease Progression; Elderly; Equilibrium; Evaluation; Exercise; Foundations; Functional Magnetic Resonance Imaging; Goals; Health; Image; Impairment; Individual; Kinetics; Laboratory Study; Lower Extremity; Magnetic Resonance Spectroscopy; Measures; Mediating; Metabolism; Methods; Microcirculation; Monitor; Muscle; Muscle function; Myopathy; Outcome; Oxygen; Oxygen Consumption; Performance; Perfusion; Peripheral; Peripheral arterial disease; Phase; Phosphocreatine; Phosphorus; Physical Function; Play; Population; Protocols documentation; Publishing; Recovery; Regulation; Rodent; Role; Severity of illness; Spectrum Analysis; Time; Tissues; Training; Vascular Diseases; Vasodilation; age effect; age related; aged; arteriole; base; blood oxygen level dependent; functional decline; improved; muscle metabolism; response; sedentary; tool; young adult

DESCRIPTION (provided by applicant): The microvasculature is critical for the control of blood flow and tissue perfusion. Compromised microvascular function occurs during aging as well as several disease states including diabetes and peripheral arterial disease and may contribute to compromised muscle performance within these populations. Unfortunately, practical measures for assessing microvascular function are lacking. With the advent of muscle functional magnetic resonance imaging (fMRI) using blood oxygen level- dependent imaging (BOLD), peripheral microvascular function can be assessed noninvasively. Our studies have shown that muscle BOLD responses are sensitive to blood volume and oxygenation changes and are increased in magnitude in young endurance trained adults when compared to sedentary adults. Preliminary data also suggest an age related decline in BOLD responses and slowing of muscle oxygen kinetics. A reduced BOLD response is important because it indicates reduced muscle perfusion which impacts muscle metabolism and muscle function. The overall purpose of these studies is to exploit muscle BOLD to assess microvascular function in elderly adults. In addition, these studies will also contribute to the understanding of the bioenergetic consequences of aging. Aim 1 will examine the effect of age on muscle BOLD by comparing single contraction mediated responses in young versus elderly adults. We will also examine the effect of age on phosphocreatine (PCr) recovery kinetics; PCr kinetics reflect oxidative ATP synthesis. These outcomes together will allow us to integrate microvascular function with oxygen consumption and ATP synthesis. Aim 2 will examine the influence of aerobic exercise on the muscle BOLD response in sedentary elderly adults. Echo planar fMRI will be used to acquire muscle BOLD images; phosphorus spectroscopy will be used to evaluate PCr kinetics. Muscle BOLD is an important measure because it reflects muscle perfusion and we suggest this is a critical parameter that is lost with aging. Imbalances between perfusion and metabolism may contribute to age related muscle impairment. Our proposed studies are consistent with an emerging consensus that the initial vascular responses are pivotal in vascular control and function. These studies will provide a strong foundation for a noninvasive assessment tool that evaluates microvascular function and will show the ability of aerobic exercise to improve microvascular function in elderly adults. As the U.S. older adult population is nearly 50 million strong and growing, understanding the factors related to poor physical function is imperative. Our long-term goal is to establish noninvasive methods for assessing microvascular and muscle function that can be used in vascular and muscle disease detection and monitoring. PUBLIC HEALTH RELEVANCE: Peripheral vascular function declines with age and may contribute to reduced muscle performance and activity limitations in aging. The function of the small blood vessels within the muscle is likely to play a role in age related functional declines. The proposed studies will evaluate a new noninvasive method for measuring microvascular function and examine the influence of aerobic exercise training on microvascular function in aging.

描述（由申请人提供）： 微血管系统对于血流和组织灌注的控制至关重要。微血管功能受损会在衰老以及包括糖尿病和外周动脉疾病在内的几种疾病状态下发生，并可能导致这些人群的肌肉性能受损。不幸的是，缺乏评估微血管功能的实用措施。随着使用血氧水平依赖性成像（BOLD）的肌肉功能磁共振成像（fMRI）的出现，可以无创地评估外周微血管功能。我们的研究表明，肌肉 BOLD 反应对血容量和氧合变化很敏感，并且与久坐的成年人相比，经过耐力训练的年轻成年人的肌肉 BOLD 反应幅度有所增加。初步数据还表明，大胆反应和肌肉氧动力学减慢与年龄相关。 BOLD 反应减少很重要，因为它表明肌肉灌注减少，从而影响肌肉代谢和肌肉功能。这些研究的总体目的是利用肌肉 BOLD 来评估老年人的微血管功能。此外，这些研究还将有助于理解衰老的生物能量后果。目标 1 将通过比较年轻人和老年人的单次收缩介导的反应来检查年龄对肌肉 BOLD 的影响。我们还将研究年龄对磷酸肌酸 (PCr) 恢复动力学的影响； PCr 动力学反映了氧化 ATP 合成。这些结果将使我们能够将微血管功能与耗氧量和 ATP 合成结合起来。目标 2 将研究有氧运动对久坐老年人肌肉 BOLD 反应的影响。回波平面功能磁共振成像将用于获取肌肉 BOLD 图像；磷光谱将用于评估 PCr 动力学。 Muscle BOLD 是一项重要指标，因为它反映了肌肉灌注，我们认为这是一个随着衰老而丢失的关键参数。灌注和代谢之间的不平衡可能导致与年龄相关的肌肉损伤。我们提出的研究与新兴共识一致，即初始血管反应对于血管控制和功能至关重要。这些研究将为评估微血管功能的无创评估工具提供坚实的基础，并将展示有氧运动改善老年人微血管功能的能力。美国老年人口已接近 5000 万，并且还在不断增长，因此了解与身体机能不良相关的因素势在必行。我们的长期目标是建立评估微血管和肌肉功能的无创方法，可用于血管和肌肉疾病的检测和监测。 公共卫生相关性： 周围血管功能随着年龄的增长而下降，可能导致衰老时肌肉性能下降和活动受限。肌肉内小血管的功能可能在与年龄相关的功能衰退中发挥作用。拟议的研究将评估一种新的无创测量微血管功能的方法，并研究有氧运动训练对衰老过程中微血管功能的影响。