Age-related alterations in cytochrome c-mediated caspase activation in rhesus macaque monkey (Macaca mulatta) brains.

Age-related changes and regional differences in caspase expression were determined in the primate brain. Using immunoblot analysis, the levels of endogenous caspase-3, caspase-9 and cytochrome c-triggered activated caspase-3 were examined in brain homogenates from the prefrontal, motor and visual cortices, cerebellum, hippocampus and amygdala of 4-year-old and 20-year-old rhesus macaques. Procaspase-3 was detected in similar quantities in all brain regions of both young and aging macaques. Being found in all brain regions, caspase-9 was significantly elevated in old macaques as compared to young ones. After incubation with cytochrome c, active forms of caspase-3 were detected in all brain regions of young and old macaques. In almost all brain regions of old monkeys, the levels of cytochrome c-dependent caspase-3 activation were higher than those of young macaques. These results suggest that the aging rhesus macaque brain has a lower threshold to apoptotic stimuli.