Functional and structural decline in the neuromuscular system with aging has been recognized as a cause of impairment in physical performance and loss of independence in the elderly. Alterations in spinal cord motor neurones and at the neuromuscular junction have been identified as evidence of denervation in skeletal muscles from aging mammals, including humans. However, the reciprocal influences of neurones on gene expression in muscle and of muscle on age-related neurodegeneration are poorly understood, and, as a result, interventions aimed at delaying or preventing degeneration of the neural component in aging muscle have been largely unsuccessful. The present article discusses the evidence for neural influence on age-related impairments of skeletal muscle, including a role in excitation-contraction uncoupling. The role of nerves in regulating the trophic actions of insulin-like growth factor-1 (IGF-1) and other neurotrophic factors is considered as a novel influence on the effects of aging on the neuromuscular junction. A better understanding of nerve-muscle interactions will allow for more rational interventions in the aging neuromuscular system.