Age-related changes in glutathione and lipid peroxide content in mouse synaptic mitochondria: relationship to cytochrome c oxidase decline.

To elucidate the contribution of lipid peroxides and glutathione to brain aging, we have carried out a comparative study of their contents in synaptic mitochondria from young (10-week-old), adult (24-week-old), and senescent (72-week-old) mice. In synaptic mitochondria, there is a significant decline in lipid peroxide content (P < 0.01) and cytochrome c oxidase activity (P < 0.001) in senescent as compared to adult and young mice. By contrast, glutathione concentration showed an increase in senescent (P < 0.05) in comparison to the other age groups. Moreover, there was a significant inverse correlation between age and lipid peroxide content (r = -0.5, P < 0.001) or cytochrome c oxidase-specific activity (r = -0.58, P < 0.001). We suggest that this age-dependent decrease in lipid peroxide content in synaptic mitochondria may be the result of an age-related decline in the activity of the electron transport chain, with concomitant decrease in oxyradical production, in the senescent organelles.