Reduced calcium uptake by rat brain mitochondria and synaptosomes in response to aging

Synaptosomes were isolated from cerebral cortex of 3-, 18- and 24-month-old male, Fisher 344 rats and 45Ca2+ uptake was measured at 1, 3, 5, 15 and 30 s time periods following 65 mM KCl depolarization. Identical experiments were performed in which 5 mM KCl was added to examine age-related changes in resting 45Ca2+ accumulation by synaptosomes. Both 'fast-' and 'slow-phase' voltage-dependent 45Ca2+ uptake were significantly reduced in synaptosomes from 18- and 24- vs 3-month-old rats. No age-related change in resting (5 mM KCl) 45Ca2+ accumulation was observed. ATP-dependent and respiration-linked 45Ca2+ uptake was examined in mitochondria isolated from whole brains of 3- and 28-month-old male, hooded Long-Evans rats. Both ATP-dependent and glutamate-malate-ADP stimulated 45Ca2+ uptake by mitochondria were markedly reduced in response to aging. Respiratory control ratios were the same for 3- and 28-month-old mitochondria, suggesting that the decrement in 45Ca2+ uptake was not caused by an age-related decline in respiratory activity of mitochondria. The results of this study show that both voltage-dependent calcium entry into presynaptic nerve terminals and calcium uptake by mitochondria in brain decline with advanced aging. Age-related changes in cytosolic calcium levels could underlie, at least in part, cellular decrements in brain observed with aging.