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: 8639634
• 负责人: Darren Patrick Casey
• 金额: $ 23.7万
• 依托单位: UNIVERSITY OF IOWA
• 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 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8639634
• 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

PROJECT SUMMARY/ABSTRACT 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.

项目总结/摘要 在动态运动骨骼肌血流量增加迅速和显着（运动 充血）以满足收缩组织的代谢需要。衰老与衰减的 动态运动时的充血反应。负责增加血流的机制 运动的开始以及在年轻人中随着时间的推移保持运动涉及以下因素之间的复杂相互作用： 机械因素、交感神经系统和局部代谢和内皮衍生物质 影响血管紧张度。运动血流量减少的机制 在老年人中的作用还不完全清楚。 申请人提出了两个主要目标：1）鉴定有助于改变血管扩张剂的机制， 老年人对单一肌肉收缩和动态运动的反应，以及2）检查效果 衰老对运动过程中骨骼肌血流/血管舒张动力学的影响K99期间/辅导 在赠款的第一阶段，申请人将检查血管中的机械，内皮和神经改变。 功能，并确定这些变化如何与衰减的快速血管扩张剂 一次肌肉收缩后的反应。在授权的R 00/独立阶段的第一部分， 申请人将检查节律性运动期间血管舒张的动力学（静止至稳态过渡 并量化衰老对这些反应的影响。在R 00阶段的第二部分，申请人 评估是否减弱血管扩张反应单肌肉收缩和较慢的动力学 在老年受试者的上肢和下肢中，有节奏运动期间的血管舒张是相似的。最后，在 在R 00阶段的第三部分，申请人将确定是否在流量变化后单 收缩和/或血管舒张的动力学是生理老化的结果或与 训练状态。总的来说，本提案中概述的实验侧重于机械， 内皮和神经的变化，发生在骨骼肌血管与老化，以及如何 这些变化影响运动肌肉中的血液流动。确定血液流向 随着年龄的增长，收缩肌肉的变化将有助于理解这些变化是否是由于 生理年龄本身或不活动的结果。 在K99/指导阶段的奖励，申请人将1）继续获得基本的专业知识， 在有意识的人类中进行综合生理学研究，2）继续学习药理学和生物化学 从机械观点研究肌肉血流控制的方法。另夕h 候选人将获得新的研究技能和先进的前沿超声技术相关的知识 和动脉特性的测量（具体地，剪切波分散超声振动测量法; SDUV）， James Greenleaf博士（共同导师）的指导。在已建立的生产性实验室进行培训， 就像迈克尔·乔伊纳博士沿着马约诊所的詹姆斯·格林里夫博士的帮助下所做的那样， 实现上述目标所需的机会。重要的是，这项培训将促进 实现申请人的长期目标，发展国际知名的独立 心血管生理学的研究项目。