The overall aims of this Program Project are to test the hypothesis that denervation changes are responsible for much of the deficit in muscle mass and function that is seen in old age and to discover enough about the biology of denervated muscle to be able to devise methods for successfully preventing or reversing the course of denervation atrophy. Project 1 will employ principally morphological methods to investigate both satellite cell biology and to localize in tissue sections important molecules in muscles at various stages of aging and denervation, as well as to asses the success of restoration of denervated and/or aging muscle by grafting or electrical stimulation. In Group Aims 1 and 2, P-1 will provide quantitative data on the numbers and distribution of satellite cells on denervated muscle fibers of young and old rats, as well as localizing by immunocytochemical means molecules of the myogenic regulatory factor family and the proteins EF-1alpha and S1. In addition, P-1 will assess morphologically the success of grafts of denervated and aged muscles into young host rats. In Group Aim 3, p-1 will use satellite cell analysis and molecular localization techniques to test the hypothesis that electrical stimulation of denervated muscle significantly reduces the rate and degree of denervation atrophy. P-1 will also assess the morphology of grafts of stimulated-denervated muscles in testing the hypothesis that grafts of stimulated-denervated muscles recover better than grafts of non-stimulated denervated muscles. For Group aim 4, P-1 will assess the morphology of grafts of muscles that have been reinnervated with either fast or slow nerves in young, adult, old and extremely old rats. These studies are expected to clarify the cellular basis underlying denervation atrophy and the patterns of recovery seen after different periods of denervation of muscle. These data will than be used in the analysis of structural and functional deficits in aging muscle.
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