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）：在动态运动期间，骨骼肌血流量快速且显着地增加（运动充血）以满足收缩组织的代谢需求。衰老与动态运动期间充血反应减弱有关。年轻人运动开始时增加血流量以及随着时间的推移维持血流量的机制涉及机械因素、交感神经系统以及影响血管张力的局部代谢和内皮衍生物质之间的复杂相互作用。观察到的老年人运动血流量减少的机制尚不完全清楚。 申请人提出了两个主要目标：1）确定导致老年人对单块肌肉收缩和动态运动的血管舒张反应改变的机制，以及2）检查衰老对运动期间骨骼肌血流/血管舒张动力学的影响。在资助的 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次肌肉收缩后快速血管舒张反应减弱之间的关系。在资助的 R00/独立阶段的第一部分，申请人将检查有节奏运动期间血管舒张的动力学（休息到稳态过渡），并量化衰老对这些反应的影响。在R00阶段的第二部分中，申请人评估老年受试者的上肢和下肢对单次肌肉收缩的减弱的血管舒张反应和节律性运动期间血管舒张的较慢动力学是否相似。最后，在 R00 阶段的第三部分，申请人将确定老年人单次收缩后的流量变化和/或血管舒张动力学是否是生理衰老的结果或与训练状态有关。总的来说，本提案中概述的实验重点关注骨骼肌脉管系统随着衰老而发生的机械、内皮和神经变化，以及这些变化如何影响运动肌肉中的血流。确定流向收缩肌肉的血流随年龄增长而改变的机制将有助于了解这些变化是由于生理年龄本身还是由于不活动造成的。 在该奖项的 K99/指导阶段，申请人将 1) 继续获得有意识的人类基础综合生理学研究的专业知识，2) 继续学习药理学和生化方法，从机械的角度研究肌肉血流的控制。此外，候选人将在 James Greenleaf 博士（共同导师）的指导下获得与先进的尖端超声技术和动脉特性测量（特别是剪切波色散超声振动测量；SDUV）相关的新研究技能和知识。在梅奥诊所的 Michael Joyner 博士等成熟且富有成效的实验室以及 James Greenleaf 博士的帮助下进行培训将为实现上述目标提供所需的机会。重要的是，本次培训将有助于申请人实现开发国际知名的心血管生理学独立研究项目的长期目标。 公共卫生相关性：进行身体活动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。衰老与动态运动期间骨骼肌血流量减少有关。有趣的是，老年人也表现出运动能力下降。该提案旨在研究限制血液流向健康老年人运动肌肉的因素。该提案产生的信息可能有助于制定旨在改善老年人身体功能的具体干预措施。