AGE-ASSOCIATED DAMAGE IN MITOCHONDRIAL-DNA IN HUMAN HEARTS

Damage to mitochondrial DNA seems to be involved in the etiology of age-associated degenerative diseases. The aim of this study is to elucidate effects of aging on human mitochondrial DNA. 8-Hydroxy-deoxyguanosine, a product of free radical damage to deoxyguanosine, is reported to cause random point mutations. In human mitochondrial DNA, 8-hydroxy-deoxyguanosine increased exponentially with age, and the population of mitochondrial DNA with deletion increased also exponentially with age. Furthermore, a clear correlation existed between the accumulation of 8-hydroxy-deoxyguanosine and that of mitochondrial DNA with deletion. We also determined the effects of aging on rat mitochondrial function together with 8-hydroxy-deoxyguanosine content in mitochondrial DNA. The activities of complexes I and IV of the mitochondrial electron transport chain decreased significantly in rats aged 100 weeks compared with those in rats aged 7 weeks. A concomitant increase in 8-hydroxy-deoxyguanosine was observed in mitochondrial DNA of rats aged 100 weeks. From our results, it is concluded that the age-associated accumulation of somatically acquired oxygen damage together with deletions in mitochondrial DNA might be important contributors to the deterioration of cardiac function associated with age.