AGE-RELATED INFLUENCES ON MUSCLE AND NERVE REGENERATION

骨骼肌和周围神经在老年人中再生更差 在幼鼠身上。根据交叉年龄嫁接获得的数据 机型中，与年龄相关的主机变化似乎会削弱容量 肌肉和神经才能再生。本计划的具体目标 项目将检验四个组假设，与旧的比较 幼年大鼠：A.肌肉移植物再生不良与缺乏有关 再支配；B.肌肉不存在结构或功能上的差异 纤维在早期的预神经支配阶段，但结构和功能 肌肉纤维和运动单位在神经支配后受损 C.轴突再生受损与神经元缺陷有关 基因表达、髓鞘清除、巨噬细胞和雪旺细胞 功能；以及D.跨年龄神经移植最终适应于 宿主的特征。假设A和B将通过以下方式进行检验 单肌纤维、运动单位和整体的生理学分析 肌肉特性、组织化学和神经染色，以及电子 显微镜。假设C和D将通过免疫细胞化学进行检验， 原位杂交、形态计量分析、放射自显影、生长 因子分析及Northern和Western印迹分析。的重要意义。 拟议的研究是对责任机制的澄清 用于改善老年动物的肌肉和神经再生。这个 这项研究的长期目标是为改善 修复老年人受损的肌肉和神经。

Skeletal muscle and peripheral nerve regenerate more poorly in old than in young rats. On the basis of data obtained from cross-age grafting models, an age-related change in the host appears to impair the capacity of muscle and nerve to regenerate. The Specific Aims of this Program Project are to test four Group Hypotheses that in old as compared with young rats: A. poor regeneration of muscle grafts is related to deficient reinnervation; B. no structural or functional differences exist in muscle fibers during an early preinnervation stage, but structure and function of muscle fibers and motor units are impaired during a postinnervation stage; C. impaired axonal regeneration is related to defects in neuronal gene expression, myelin clearance, and macrophage and Schwann cell function; and D. cross-age nerve grafts ultimately become adapted to characteristics of the host. Hypotheses A and B will be tested by physiological analysis of single muscle fiber, motor unit and whole muscle properties, histochemistry and nerve staining, and electron microscopy. Hypotheses C and D will be tested by immunocytochemistry, in situ hybridization, morphometric analysis, autoradiography, growth factor analysis and Northern and Western blotting. The significance of the proposed research is the clarification of the mechanisms responsible for the improvement of muscle and nerve regeneration in old animals. The long-term goal of this research is to provide the basis for improving the repair of damaged muscle and nerve in old individuals.