Impact of Aging on Skeletal Muscle Blood Flow Kinetics During Exercise

衰老对运动过程中骨骼肌血流动力学的影响

• 批准号: 8189535
• 负责人: Darren Patrick Casey
• 金额: $ 8.56万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8189535
• 关键词: Achievement; Address; Adrenergic Agents; Age; Aging; Attention; Attenuated; Award; Biochemical; Biological Availability; Blood Vessels; Blood flow; Cardiovascular Physiology; Clinic; Complex; Conscious; Contracts; Controlled Study; Data; Educational Status; Elderly; Exercise; Forearm; Gender; Goals; Grant; Heterogeneity; Human; Hyperemia; Individual; Intervention; Kinetics; Knowledge; Laboratories; Learning; Leg; Life; Limb structure; Literature; Lower Extremity; Measures; Mechanics; Mediating; Mentors; Mentorship; Metabolic; Muscle; Muscle Contraction; Nitric Oxide; Oxygen; Oxygen Consumption; Phase; Physical Function; Physical activity; Physiological; Physiology; Property; Publishing; Regulation; Research; Resistance; Rest; Skeletal Muscle; Speed; Structure; Sympathetic Nervous System; Techniques; Time; Tissues; Training; Ultrasonography; United States National Institutes of Health; Upper Extremity; Vasodilation; Vasodilator Agents; Work; adrenergic; age effect; aged; arm; arterial stiffness; healthy aging; improved; innovation; meetings; programs; relating to nervous system; research study; response; sedentary; skills; viscoelasticity; young adult

DESCRIPTION (provided by applicant): During dynamic exercise skeletal muscle blood flow increases rapidly and dramatically (exercise hyperemia) to meet the metabolic needs of the contracting tissue. Aging is associated with an attenuated hyperemic response during dynamic exercise. The mechanisms responsible for increasing blood flow at the onset of exercise as well as maintaining it over time in young adults involves a complex interaction between mechanical factors, the sympathetic nervous system and local metabolic and endothelial derived substances that influence vascular tone. The mechanisms responsible for the observed reductions in exercise blood flow in older humans are not completely clear. The applicant proposes two main goals: 1) to identify mechanisms contributing to the altered vasodilator responses to single muscle contractions and dynamic exercise in aging humans, and 2) to examine the effect of aging on the kinetics of skeletal muscle blood flow/vasodilation during exercise. During the K99/Mentored phase of the grant, the applicant will examine the mechanical, endothelial, and neural alterations in vascular function that occur with aging and determine how these changes relate to the attenuated rapid vasodilator response following a single muscle contraction. In the first portion of the R00/Independent phase of the grant, the applicant will examine the kinetics (rest to steady state transition) of vasodilation during rhythmic exercise and quantify the effects of aging on these responses. In the second portion of the R00 phase, the applicant evaluate whether the attenuated vasodilator response to single muscle contractions and slower kinetics of vasodilation during rhythmic exercise are similar in the upper and lower limbs of older subjects. Lastly, in the third portion of the R00 phase, the applicant will determine whether the changes in flow following single contractions and/or the kinetics of vasodilation in older humans is a result of physiological aging or related to training status. Collectively, the experiments outlined in this proposal focus on the mechanical, endothelial, and neural alterations that occur in the skeletal muscle vasculature with aging and how these changes impact blood flow in exercising muscle. Identifying the mechanisms by which blood flow to contracting muscles is altered with advancing age will help in understanding whether these changes are due to physiological age per se or a result of inactivity. During the K99/Mentored phase of the award the applicant will 1) continue to gain expertise in basic integrative physiology studies in conscious humans, and 2) continue to learn pharmacological and biochemical approaches to study the control of muscle blood flow from a mechanistic standpoint. Additionally, the candidate will gain new research skills and knowledge related to advanced cutting-edge ultrasound techniques and measures of arterial properties (specifically, Shearwave Dispersion Ultrasound Vibrometry; SDUV) under the mentorship of Dr. James Greenleaf (co-mentor). Training in an established and productive laboratory such as that of Dr. Michael Joyner along with the help of Dr. James Greenleaf at the Mayo Clinic will provide opportunities needed to achieve the goals listed above. Importantly, this training will facilitate the achievement of the applicant's long-term goal to develop an internationally-renowned independent research program in cardiovascular physiology. PUBLIC HEALTH RELEVANCE: The ability to perform physical activity and exercise are or should be essential components of everyday life. For exercise to be performed there must be adequate blood flow to the exercising muscles. Aging is associated with a reduced skeletal muscle blood flow during dynamic exercise. Interestingly, older individuals also demonstrate a reduced exercise capacity. This proposal seeks to study the factors that limit blood flow to exercising muscles in otherwise healthy aging humans. Information generated from this proposal might prove to be useful in developing specific interventions aimed at improving physical function in older adults.

描述（由申请人提供）：在动态运动过程中，骨骼肌的骨骼肌肉流动迅速和急剧增加（运动充血），以满足收缩组织的代谢需求。衰老与动态运动过程中的高血流动反应有关。导致运动开始时增加血液流动以及随着时间的流逝的机制涉及机械因素之间的复杂相互作用，交感神经系统与局部代谢和内皮派生的物质，影响血管张力。导致年龄较大的人类运动血流减少的机制尚不完全清楚。 申请人提出了两个主要目标：1）确定导致血管舒张器对单个肌肉收缩的反应改变的机制和人类衰老的动态运动，以及2）检查衰老对运动过程中骨骼肌血流/血管舒张动力学的影响。在赠款的K99/指导阶段，申请人将检查随着衰老而发生的血管功能的机械，内皮和神经变化，并确定这些变化与单个肌肉收缩后减毒的快速血管静脉反应有关。在赠款的R00/独立阶段的第一部分中，申请人将检查节奏运动过程中血管舒张的动力学（静态到稳态过渡），并量化衰老对这些反应的影响。在R00阶段的第二部分中，申请人评估了在节奏运动过程中对单肌收缩的血管舒张反应和血管舒张动力学较慢的反应在旧受试者的上肢和下肢中相似。最后，在R00阶段的第三部分中，申请人将确定年龄较大人类的单个收缩和/或血管舒张动力学后流量变化是生理衰老还是与训练状态有关的结果。总的来说，该提案中概述的实验集中在骨骼肌脉管系统中发生的机械，内皮和神经改变，以及这些变化如何影响锻炼肌肉的血液流动。随着年龄的增长，确定血液流向收缩肌肉的机制将有助于理解这些变化是由于生理年龄本身而引起的还是无效的结果。 在奖励的K99/指导阶段，申请人将继续获得有意识人类的基本综合生理研究的专业知识，2）继续学习药理和生化方法，从机械角度研究肌肉血流的控制。此外，候选人将在James Greenleaf博士（Co-Mentor）的指导下获得与先进的尖端超声技术和动脉特性的测量（特别是剪切波分散超声振动学； SDUV）有关的新研究技能和知识。在梅奥诊所的詹姆斯·格林利夫（James Greenleaf）博士的帮助下，在诸如迈克尔·乔伊纳（Michael Joyner）博士的既定且生产性实验室的培训将提供实现上述目标所需的机会。重要的是，这项培训将有助于实现申请人的长期目标，以制定国际知名的心血管生理学独立研究计划。 公共卫生相关性：进行体育锻炼和锻炼的能力是或应该是日常生活的重要组成部分。为了进行运动，必须有足够的血液流向运动肌肉。衰老与动态运动过程中的骨骼肌血流减少有关。有趣的是，老年人也表现出降低的运动能力。该提案旨在研究限制血液流动到其他健康衰老的人的肌肉的因素。该提案产生的信息可能被证明可用于开发旨在改善老年人身体功能的特定干预措施。