Microcirculation in Aging Skeletal Muscle

描述：(申请人提供)体力活动能力为 随着年龄的增长而减少。尽管很大程度上归因于骨质疏松症(质量减少 和骨骼肌的质量)，对衰老如何影响肌肉知之甚少 血液流动和氧气供应。我们的工作假设是， 供应骨骼肌纤维的微循环随着年龄的增长而受损， 对肌肉功能的不利影响。基于蓬勃发展的 在小鼠系统的基因组策略中，C57BL/6小鼠将被开发出来 在这里作为一个模特。我们的目标是定义结构中发生的变化 以及骨骼肌微循环随年龄增长而发生的功能。 肌肉中的血管传导性似乎随着年龄的增长而减少；然而， 潜在的结构和功能适应问题尚未解决。因此， 利用血管铸型和组织学，目标1是确定微血管 老化会改变组织的拓扑和形态。很少有人知道衰老是如何发生的 影响肌肉纤维收缩、代谢之间的相互作用 血管扩张和氧气输送。因此，目标2是确定效果 衰老对小动脉张力、反应性和毛细血管血流的影响。使用 提睾肌准备，活体显微镜将决定是否 对内皮依赖性或非依赖性血管扩张剂的反应受损 从而定义微血管对肌肉纤维收缩的反应 可能是钝化的。在运动中，心输出量的重新分配到 活跃的骨骼肌与微血管灌注压的维持 是通过交感神经活动来控制的。而交感神经的变化 神经效应通路已经推断，衰老对能力的影响 交感神经控制小动脉和小静脉的作用尚不清楚。因此， 目的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心 血管收缩，区分这种变化是否是由于释放的改变 神经递质与微血管平滑肌抑制反应的关系 细胞，并确定衰老对血管运动反应的影响是否 神经递质是儿茶酚胺所特有的。定义这些关键字 对照(C57BL/6)小鼠的关系将产生机械性假说 重点关注衰老如何影响细胞和分子信号通路 这决定了微血管的结构和功能。我们的长期目标是 应用生理基因组学开发新的最小化策略 衰老对肌肉功能和体力活动的不利影响 从而保持生活质量。

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.