Dysregulated cholinergic transmission contributes to aging of the lower motor system

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Project Summary/ Abstract The loss of motor function that occurs with aging is closely associated with adverse health outcomes. To date, the contribution of different components of the motor system to age-related motor deficits remains unknown and despite extensive efforts. In addition, there are no therapeutics that can prevent the cellular and molecular changes that underlie loss of motor function with aging. The purpose of this proposal is to identify the contribution of the neuromuscular system to loss of motor function. We also seek to identify and test factors that function to maintain healthy skeletal muscles and motor neurons in the spinal cord, and thus preserve motor function. Specifically, we will determine whether maintaining normal levels of acetylcholine, genetically and pharmacologically, is sufficient to slow aging of skeletal muscle and motor neurons.