The overall aim of this Program Project is to test the hypothesis that the poor regeneration of skeletal muscle in old rats is due to a great extent to deficient reinnervation. By means of quantitative morphological methods, Project #1 will investigate aspects of deficient reinnervation of muscle grafts in old as compared with young rats by testing four hypotheses: A) In old rats, deficient reinnervation is reflected in delayed reinnervation of muscle and a reduced number of neuromuscular junctions in whole muscle grafts. B) If the age-related influence on muscle regeneration is heavily influenced by the nerve, two identifiable stages in the muscle regeneration process can be identified - a preinnervation stage in the muscle regeneration does not differ between old and young rats and a postinnervation stage in which structural deficiencies will be apparent in muscle fibers of old rats. C) Schwann cell proliferation, as part of a mechanism supporting axonal regeneration, is reduced in transected nerves in old rats. D) Through macroenvironmental influences from the host, the level of Schwann cell proliferation in nerve grafts will correspond to that appropriate to the age of the host. To test these hypotheses, muscle grafts will be analyzed by means of histology, histochemistry, nerve staining, electron microscopy, autoradiography and morphometric methods. The hypotheses will be supported if the data obtained show the postulated reductions in structural properties of muscles and muscle fibers and proliferative properties of Schwann cells in old rats. These studies are expected to clarify the basis for the poor regeneration of skeletal muscle in old individuals, and this information could be used to improve the recovery of injured muscle in old patients.
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