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.
Hayakawa
M
M
Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
Sugiyama
S
S
Hattori
K
K
Takasawa
M
M
Ozawa
T
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000375:Aging; D000818:Animals; D001483:Base Sequence; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004579:Electron Transport; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D051381:Rats
D004272:DNA, Mitochondrial; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine