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Abstract Objective To test whether the normal aging itself may change the cortical plasticity in human. Methods Motor-evoked potentials (MEPs) were measured from 48 right-handed healthy volunteers (age 21–79) before and after the paired associative stimulation (PAS), comprising a single electric stimulus to the right median nerve at wrist and subsequent transcranial magnetic stimulation (TMS) of the left primary motor cortex. Results The magnitude of MEP increased by PAS in the young and middle but not in the elderly and its change was negatively correlated with the age. Conclusions These results suggest that the human M1 shows age-dependent reduction of cortical plasticity. Significance The reduction of the M1 plasticity may be caused by the attenuated responsiveness of intracortical circuits in the M1 and/or disrupted sensorimotor integration within basal ganglia-thalamocortical loop.