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: 8656404
• 负责人: Darren Patrick Casey
• 金额: $ 24.4万
• 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/8656404
• 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/文摘