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There is controversy whether age-related neuroanatomical and neurophysiological changes in the central nervous system affect healthy old adults' abilities to acquire and retain motor skills. We examined the effects of age on motor skill acquisition and retention and potential underlying mechanisms by measuring corticospinal and intracortical excitability, using transcranial magnetic stimulation. Healthy young (n = 24, 22 years) and old (n = 22, 71 years) adults practiced a wrist flexion-extention visuomotor task or only watched the templates as an attentional control for 20 minutes. Old compared with young adults performed less well at baseline. Although the absolute magnitude of skill acquisition and retention was similar in the 2 age groups (age × intervention × time, p = 0.425), a comparison of baseline-similar age sub-groups revealed impaired skill acquisition but not retention in old versus young. Furthermore, the neuronal mechanisms differed as revealed by an opposite direction of associations in the age-groups between relative skill acquisition and intracortical facilitation during the task, and opposite changes during skill retention in corticospinal excitability at rest and during the task and intracortical inhibition during the task., (Copyright © 2016 Elsevier Inc. All rights reserved.)