Age-related alterations in mitochondrial physiological parameters and nitric oxide production in synaptic and non-synaptic brain cortex mitochondria.

Brain aging has been associated with mitochondrial dysfunction and changes in nitric oxide levels. The aim of this study was to evaluate the susceptibility of synaptic and non-synaptic mitochondria to aging-dependent dysfunction. State 3 respiratory rate and respiratory control were 43% and 33% decreased, respectively in brain cortex synaptosomes from 14-month-old animals, as compared with synaptosomes from 3-month-old mice. Respiratory rates were not significantly affected by aging in non-synaptic mitochondrial fractions. Mitochondrial dysfunction was associated with increases of 84% and 38% in H₂O₂ production rates in brain cortex synaptosomes and non-synaptic mitochondria, respectively, from 14-month-old mice, as compared with young animals. Synaptic mitochondria seem to be more susceptible to calcium insult in 14-month-old mice, as compared with non-synaptic mitochondria, as measured by response of both types of fractions to calcium-induced depolarization. With aging, nitric oxide (NO) production was 44% and 27% decreased both in synaptosomal and non-synaptic mitochondrial fractions, respectively. The results of this study suggest that with aging, mitochondrial function at the nerve terminals would be more susceptible to suffer alterations by the constant calcium changes occurring as a consequence of synaptic activity. Non-synaptic mitochondria would be more resistant to age-related dysfunction and oxidative damage.