The goal of this program is to elucidate age-related changes in neurons which are likely to be involved in the reduced functional capacity of the nervous system in aged humans. The program combines the approaches of morphology, electrophysiology and molecular biology to study the capacity of aging neurons to maintain and regenerate axons and synaptic connections. Three model systems will be employed: the mammalian neuromuscular systems, we will define certain changes which occur as a result of aging, altered usage, loss of afferent input, or reinnervation. In order to elucidate the underlying molecular processes which give rise to these changes, we will determine the possible synapses, by altering usage or type or innervation. The amphibian systems will be used to explore neurotrophic capacity as a function of age, and the role of ependymal cells, in regeneration of central connections. Information regarding the cellular and biochemical mechanisms which give rise to age-changes in neurons will be important in our eventual understanding of the aging process in the human nervous system. Furthermore, the possibility of reversing certain aging changes in the nervous system, which will explored in some of these studies, has important implications.