MUSCLE CONTRACTILITY--DENERVATION AND AGING

所提出的实验是由工作假设驱动的， 的结构和功能特性的主要递减 骨骼肌发生在成熟和老年之间，以及 特别是在老年和极端老年之间， 肌肉纤维的去神经支配。 具体的假设是 制定了探测手术的细胞和分子生物学- 在年轻大鼠中诱导的去神经和在年龄诱导的去神经中 34个月大的老鼠 #2项目将有助于整体 通过制定电刺激方案实现目标 植入式微刺激器的失神经肌肉;以及 单根纤维机械性能的测量，电动机部件 和整个肌肉，肌肉移植，和非刺激， 刺激失神经肌肉 去神经后，特定时间 周期对于细胞和分子事件至关重要， 结构和功能恢复：在10天内， 级联反应改变EF 1 α、S1、nAChR的表达水平 同种型和MRF;并且在1个月内，70%的肌肉质量和 失去了90%的力量。 与即刻神经再支配相比 肌肉，去神经支配2个月后的神经再支配导致 100%恢复，但4个月后恢复福尔斯降至40%， 7个月后。 对失神经肌肉的电刺激 肌肉质量为对照值的70%，力为对照值的50%。 基于 这些观察结果，无论是非刺激和刺激-去神经 肌肉将在10天、1、2、4和7个月后进行研究。 项目#2将在形态细胞的相关性方面进行合作， 和分子事件的缺陷和恢复的力量和权力， 非刺激-去神经和刺激-去神经肌肉。 的 要检验的假设是，选择性去神经支配快纤维， 与老老鼠相比， 运动单位丧失和重塑 严重的运动单位损失也是 预期在移植来自极老年人的EDL肌肉后， 相比之下，老年供体大鼠进入年轻的宿主。 的相互作用 快和慢纤维类型，快和慢运动神经，以及年龄 大鼠的神经再支配和再生将取得成功 研究通过自我神经支配和交叉神经支配的 跖肌和比目鱼肌的自体移植。 细胞的结合 和分子探针以及信号传递过程， 单位和整个肌肉结构-功能关系提供了一个 分层的方法，承诺对年龄的重要新见解- 诱发骨骼肌失神经萎缩。

The experiments proposed are driven by the working hypothesis that the major decrements in the structural and functional properties of skeletal muscles that occur between maturity and old age, and particularly between old age and extreme old age, are a function of denervation of muscle fibers. Specific hypotheses have been formulated to probe the cellular and molecular biology of surgically- induced denervation in young rats and of age-induced denervation in extremely-old 34 month rats. Project #2 will contribute to the Overall Goals through the development of protocols for electrical stimuation of denervated muscles with implantable microstimulators; and the measurement of mechanical properties of single fibers, motor units and whole muscles, muscle grafts, and both nonstimulated and stimulated denervated muscles. Following denervation, specific time periods are critical for cellular and molecular events underlying structural and functional recovery: within 10 days, the signaling cascades change the levels of expression of EF1alpha, S1, nAChR isoforms, and MRFs; and within 1 month, 70% of the muscle mass and 90% of the force are lost. Compared with immediately reinnervated muscles, reinnervation following 2 months of denervation results in 100% recovery, but recovery falls to 40% after 4 months and 20% after 7 months. Electrical stimulation of denervated muscles maintains muscle mass at 70% and force at 50% of control value. Based on these observations, both nonstimulated and stimulated-denervated muscles will be studied after periods of 10 days, 1, 2, 4 and 7 months. Project #2 will collaborate in the correlation of morphological cellular and molecular events with deficits and recovery in force and power of nonstimulated-denervated and stimulated-denervated muscles. The hypothesis to be tested is that selective denervation of fast fibers in muscles of extremely-old compared wit old rats will cause dramatic motor unit loss and remodeling. Severe motor unit loss is also expected following the grafting of EDL muscles from extremely old compared with old donor rats into young hosts. The interactions of fast and slow fiber types, fast and slow motor nerves, and the age of the rats on the success of reinnervation and regeneration will be investigated through self-innervation and cross-innervation of autografts of plantaris and soleus muscles. The combination of cellular and molecular probes and signaling processes with single fiber, motor unit and whole muscle structure-function relationships provides an hierarchical approach which promises significant new insights into age- induced denervation atrophy of skeletal muscle.