This study has shown that in aged rat brain (22-24 months) crude synaptosomes in comparison to that in young animals (4-6 months), a striking decrease in the activity of Na+,K+-ATPase occurs along with decreased Km and Vmax but without any change in enzyme content as seen by immunoblotting. This is associated with an accumulation of peroxidative damage products in aged brain. When rats are given antioxidant supplementation in the diet with a combination of N-acetylcysteine, α-tocopherol and α-lipoic acid daily from 18 months onwards and sacrificed at 22-24 months for experimentation, the age associated decrease of Na+, K+-ATPase activity, alterations of its kinetic parameters and accumulation of peroxidative damage products in brain synaptosomes are prevented nearly completely. Because of the critical importance of Na+,K+-ATPase in neuronal functions, the results of this study may be of potential implications in controlling age-related functional deficits of the brain. © Springer Science+Business Media B.V. 2008.