MUSCLE CONTRACTILITY--DENERVATION AND AGING

提出的实验是由工作假设驱动的，即 在结构和功能性能方面的主要下降 骨骼肌出现在成熟和老年之间，以及 尤其是在老年和极端老年之间，是一种 肌肉纤维的失神经。具体的假设是 为探索外科手术的细胞和分子生物学而制定的- 幼年大鼠失神经和增龄大鼠失神经作用 非常大的34月龄大鼠。2号项目将对整体 通过开发电刺激方案来实现目标 可植入微刺激器的失神经肌肉；以及 单纤维、电机组件力学性能的测量 以及完整的肌肉，肌肉移植，以及非刺激和 刺激失去神经的肌肉。在去神经后，特定的时间 周期对于潜在的细胞和分子事件是关键的 结构和功能恢复：在10天内，信号 级联反应改变EF1α、S1、nAChR的表达水平 异构体和MRF；在1个月内，70%的肌肉和 90%的部队都失去了。与立即恢复神经状态相比 肌肉，失神经2个月后的再神经支配会导致 100%恢复，但4个月后恢复至40%，4个月后恢复20% 7个月后。电刺激失神经肌肉维持 肌肉质量为控制值的70%，力量为控制值的50%。基于 这些观察，无论是非刺激的还是刺激的-去神经的 肌肉研究将在10天、1个月、2个月、4个月和7个月后进行。 项目2将在形态细胞的关联方面进行合作 和分子事件中的缺陷和恢复的力量和力量 非刺激去神经肌肉和刺激去神经肌肉。这个 有待检验的假说是，快速纤维的选择性去神经作用 与老年大鼠相比，极老大鼠的肌肉会引起戏剧性的 运动单位丢失和重塑。严重的运动单位损失也是 预计在移植极老的EDL肌肉后 与老年供体大鼠相比较，将其转化为年轻宿主。的相互作用 快和慢纤维类型，快和慢运动神经，以及 大鼠就成功地进行了神经再支配和再生 自体神经支配和交叉神经支配的研究 自体足底和比目鱼肌移植。蜂窝技术的结合 以及分子探针和单光纤、马达的信号传递过程 单位和整个肌肉的结构-功能关系提供了 分层方法，承诺对时代有重要的新见解- 诱导骨骼肌失神经萎缩。

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.