Microcirculation in Aging Skeletal Muscle

衰老骨骼肌的微循环

• 批准号: 6431095
• 负责人: STEVEN S SEGAL
• 金额: $ 22.47万
• 依托单位: JOHN B. PIERCE LABORATORY, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6431095
• 关键词: aging; arterioles; biological models; capillary; catecholamines; hemodynamics; histology; intravital microscopy; laboratory mouse; microcirculation; morphology; morphometry; muscle contraction; muscle function; neuroregulation; neurotransmitters; norepinephrine; oxygen transport; striated muscles; sympathetic nervous system; tissue /cell preparation; vascular endothelium; vascular resistance; vascular smooth muscle; vasodilation

DESCRIPTION: (provided by applicant) The capacity for physical activity is diminished with aging. Though largely attributed to sarcopenia (reduced mass and quality of skeletal muscle), little is known of how aging influences muscle blood flow and oxygen supply. Our working hypothesis is that the ability of the microcirculation to supply skeletal muscle fibers is impaired with aging, with adverse consequences on muscle function. Based upon the burgeoning development of genomic strategies in murine systems, the C57BL/6 mouse will be developed here as a model. Our goal is to define the changes that occur in the structure and function of the microcirculation in skeletal muscle that occur with aging. Vascular conductance in muscle appears diminished with aging; however, the underlying structural and functional adaptations are unresolved. Therefore, using vascular casting and histology, Aim 1 is to determine how micro vascular topology and morphology are altered by aging. Little is known of how aging influences the interaction between muscle fiber contraction, metabolic vasodilation, and oxygen delivery. Therefore, Aim 2 is to determine the effect of aging on arteriolar tone, reactivity and capillaty perfusion. Using the cremaster muscle preparation, intravital microscopy will determine whether responses to endothelium-dependent or -independent vasodilators are impaired and thereby define how microvascular responsiveness to muscle fiber contraction may be blunted. During exercise, both the redistribution of cardiac output to active skeletal muscle and the maintenance of microvascular perfusion pressure are governed through sympathetic nerve activity. Whereas changes in sympathetic neuroeffector pathways have been inferred, the effect of aging on the ability of sympathetic nerves to govern arterioles and venules is unknown. Therefore, Aim 3 is to determine the effect of aging on neural control of microvascular resistance and capacitance. We will test whether aging impairs sympathetic vasoconstriction, distinguish whether such changes are due to altered release of neurotransmitter vs. depressed responsiveness of microvascular smooth muscle cells, and determine whether the effects of aging on vasomotor responses to neurotransmitters are unique to catecholamines. Defining these key relationships in control (C57BL/6) mice will generate mechanistic hypotheses focused on how aging influences the cellular and molecular signaling pathways that dictate microvascular structure and function. Our long-term goal is to apply physiological genomics towards developing novel strategies for minimizing the adverse consequences of aging on muscle function and physical activity and to thereby preserve the quality of life.

描述：（由申请人提供）体育锻炼的能力是 随着衰老而减少。尽管主要归因于肌肉减少症（质量减少 骨骼肌肉的质量），对衰老如何影响肌肉知之甚少 血流和氧气供应。我们的工作假设是 微循环以提供骨骼肌纤维的衰老受损， 对肌肉功能的不利后果。基于新兴的发展 在鼠系统中的基因组策略中，将开发C57BL/6小鼠 在这里作为模型。我们的目标是定义结构中发生的变化 与衰老发生的骨骼肌中微循环的功能。 肌肉中的血管电导似乎随着衰老而减少。但是， 基本的结构和功能适应尚未解决。所以， AIM 1使用血管铸造和组织学，是确定微血管的方式 拓扑和形态会因衰老而改变。对衰老的年龄知之甚少 影响肌肉纤维收缩，代谢之间的相互作用 血管舒张和氧递送。因此，目标2是确定效果 衰老的动脉张力，反应性和毛细血管灌注。使用 Cremaster肌肉制备，插入式显微镜将确定是否是否 对内皮依赖性或非依赖性血管扩张剂的反应受损 从而定义了微血管对肌肉纤维收缩的反应 可能很钝。在锻炼过程中，心输出量的重新分配至 活跃的骨骼肌和微血管灌注压力的维持 通过交感神经活动来控制。而同情的变化 已经推断出神经射击器途径，衰老对能力的影响 尚不清楚控制动脉和静脉的交感神经。所以， 目标3是确定衰老对微血管神经控制的影响 电阻和电容。我们将测试衰老是否会损害同情 血管收缩，区分此类更改是否是由于释放的变化 神经递质与微血管平滑肌的抑郁反应能力 细胞，并确定衰老对血管舒适反应的影响是否 神经递质是儿茶酚胺独有的。定义这些钥匙 控制中的关系（C57BL/6）小鼠将产生机械假设 专注于衰老如何影响细胞和分子信号通路 这决定了微血管结构和功能。我们的长期目标是 将生理基因组学应用于制定新型策略以最大程度地减少 衰老对肌肉功能和体育锻炼的不利后果以及 从而保留生活质量。