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）体力活动能力是 随着年龄的增长而减少。虽然很大程度上归因于肌肉减少症（减少的质量 和骨骼肌的质量），很少有人知道衰老如何影响肌肉 血液流动和氧气供应。我们的工作假设是， 随着年龄的增长，供应骨骼肌纤维的微循环受损， 对肌肉功能的不良影响。基于新兴的发展 在小鼠系统中的基因组策略，C57 BL/6小鼠将被开发 在这里作为一个模型。我们的目标是定义结构中发生的变化 以及骨骼肌微循环的功能。 随着年龄的增长，肌肉中的血管传导似乎减少;然而， 潜在的结构和功能适应尚未解决。因此，我们认为， 使用血管铸型和组织学，目的1是确定微血管 拓扑结构和形态学因老化而改变。人们对衰老 影响肌纤维收缩、代谢 血管舒张和氧气输送。因此，目标2是确定效果 老化对小动脉张力、反应性和毛细血管灌注的影响。使用 提睾肌准备、活体显微镜检查将确定是否 对内皮依赖性或非依赖性血管扩张剂的反应受损 从而确定微血管对肌纤维收缩的反应 可能会变钝。在运动过程中，心输出量的重新分配， 活动骨骼肌和微血管灌注压的维持 是由交感神经活动控制的而交感神经系统的变化 神经效应通路已经推断，老化对能力的影响 交感神经支配小动脉和小静脉的机制尚不清楚。因此，我们认为， 目的3：探讨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 血管收缩，区分这种变化是否是由于改变释放 微血管平滑肌的神经递质与抑制反应性 细胞，并确定是否老化对血管反应的影响， 神经递质是儿茶酚胺所特有的。定义这些键 对照组（C57 BL/6）小鼠的关系将产生机制假设 专注于衰老如何影响细胞和分子信号通路 决定了微血管的结构和功能我们的长期目标是 将生理基因组学应用于开发新的策略， 衰老对肌肉功能和身体活动的不利影响， 从而保持生活质量。