Aging and Microvascular Dysfunction in Human Skeletal Muscle

人体骨骼肌的衰老和微血管功能障碍

• 批准号: 7770776
• 负责人: WILLIAM G SCHRAGE
• 金额: $ 17.79万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-15 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7770776
• 关键词: Address; Adult; Age; Aging; Arteries; Biochemical; Biological Availability; Biopsy; Blood Vessels; Blood flow; Diabetes Mellitus; Doctor of Philosophy; Elderly; Endothelium; Exercise; Exhibits; Forearm; Functional disorder; Glutathione; Goals; Human; Hypertension; Intervention; Leg; Mediating; Methods; Muscle; Muscle Fibers; Muscle Proteins; NADPH Oxidase; Nitric Oxide; Nitric Oxide Synthase Type I; Oxidative Stress; Population; Principal Investigator; Production; Prostacyclin synthase; Prostaglandin-Endoperoxide Synthase; Prostaglandins; Proteins; Public Health; Quality of life; Regulation; Research; Resistance; Rest; SOD2 gene; Signal Transduction; Skeletal Muscle; Structure; Superoxides; Testing; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Xanthine Oxidase; cardiovascular risk factor; catalase; design; diabetic; functional restoration; improved; improved functioning; insight; novel; prevent; programs; protein expression; public health relevance; quadriceps muscle; research study; vasoconstriction; young adult

DESCRIPTION (provided by applicant): The expanding population of aging adults is predicted to create a large public health burden in the next few decades. Older humans also exhibit reduced exercise capacity and lower muscle blood flow during exercise. The overall goal of this research program is to investigate the age-induced changes in microvascular structure, function and protein expression contributing to impaired muscle blood flow in older adults. This proposal seeks to directly test vascular control in human skeletal muscle resistance arteries (RAs) from quadriceps of young and older (e60 years) adults. The general hypothesis is that endothelium dependent dilation (EDD) is impaired via reductions in nitric oxide (NO) bioavailability and a shift away from cyclooxygenase (COX)-derived vasodilator prostaglandins (PGs) to increased vasoconstrictor PGs. This shift is due in part to increases in oxidative stress. These observations were made in resting forearms, so it remains unknown whether vascular dysfunction is occurring in the leg of older adults. The methods employed to address these aims involve muscle biopsies to investigate mechanisms that control of resistance arteries from young and older healthy humans. We have several exciting preliminary findings that support our hypotheses, and lay the groundwork for a complete R01 application in 1-2 years. The findings from these studies will provide novel insight into the regulation of muscle blood flow and vascular control in aging humans, and also could provide treatment interventions to improve muscle blood flow and exercise intolerance in diseased populations that also demonstrate endothelial dysfunction (e.g., diabetics or hypertensives). PUBLIC HEALTH RELEVANCE: Aging adults exhibit poor exercise capacity which reduces quality of life and increases cardiovascular risk. The studies in this application are designed to understand the potential contribution of impaired blood vessel function to limitations in blood flow and therefore exercise intolerance in older adults. The findings of how aging changes blood vessel function and protein expression will provide ideas on how to prevent or improve function, in an effort to restore the quality of life of older adults. The findings from these studies will provide novel insight into the regulation of muscle blood flow and vascular control in aging humans, and also could provide treatment interventions to improve muscle blood flow and exercise intolerance in diseased populations that also demonstrate poor blood vessel function (e.g., diabetes or high blood pressure).

描述（由申请人提供）：预计老年人人口的不断扩大将在未来几十年内造成巨大的公共卫生负担。老年人在运动过程中也表现出运动能力降低和肌肉血流量降低。该研究项目的总体目标是研究年龄引起的微血管结构、功能和蛋白质表达的变化，这些变化有助于老年人肌肉血流受损。该提案旨在直接测试年轻和老年（e60岁）成人四头肌的人体骨骼肌阻力动脉（RA）中的血管控制。一般假设是内皮依赖性舒张（EDD）通过一氧化氮（NO）生物利用度的降低和从环氧合酶（考克斯）衍生的血管扩张剂前列腺素（PGs）向增加的血管收缩剂PGs的转移而受损。这种转变部分是由于氧化应激的增加。这些观察是在休息的前臂上进行的，因此尚不清楚老年人的腿部是否发生血管功能障碍。用于解决这些目标的方法包括肌肉活检，以研究控制年轻和老年健康人阻力动脉的机制。我们有几个令人兴奋的初步发现，支持我们的假设，并奠定了一个完整的R 01应用在1-2年的基础。这些研究的发现将为老年人肌肉血流和血管控制的调节提供新的见解，并且还可以提供治疗干预措施，以改善也表现出内皮功能障碍的患病人群的肌肉血流和运动不耐受（例如，糖尿病患者或高血压患者）。公共卫生相关性：老年人的运动能力较差，这会降低生活质量并增加心血管风险。本申请中的研究旨在了解血管功能受损对血流受限的潜在影响，从而了解老年人的运动不耐受。衰老如何改变血管功能和蛋白质表达的研究结果将为如何预防或改善功能提供思路，以恢复老年人的生活质量。这些研究的发现将为老年人肌肉血流和血管控制的调节提供新的见解，并且还可以提供治疗干预措施，以改善也表现出血管功能差的患病人群（例如，糖尿病或高血压）。