Age-associated damage in mitochondrial function in rat hearts.

The aim of this study is to elucidate effects of aging on mitochondrial function and mitochondrial DNA (mtDNA) in rat heart and liver. The activities of complex I and complex IV of heart mitochondria of rats aged 100 weeks decreased significantly by 31% and 22%, respectively, compared with those of rats aged 7 weeks. No significant changes were observed in these two parameters in rats aged 7 weeks and aged 55 weeks. There were no significant differences in the specific activities of complex II and complex III among the age groups of 7, 55, and 100 weeks. The mtDNA content decreased by 58% in rats aged 100 weeks compared with that in rats aged 7 weeks. Content of 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative product of deoxyguanosine (dG), increased by 130% in rats aged 100 weeks compared with that in rats aged 7 weeks. No significant changes were observed in these parameters between rats aged 7 weeks and 55 weeks. In contrast to heart mtDNA, these age-dependent changes were not observed in liver mitochondria at rats aged up to 100 weeks. From our results, age-associated decline in mitochondrial function might play an important role in cell aging, particularly in postmitotic cells such as heart muscle, and accumulation of oxidative damage to mtDNA might be involved in this mechanism.