Non-linear accumulation of 8-hydroxy-2'-deoxyguanosine, a marker of oxidized DNA damage, during aging

Damage to DNA seems to be involved in aging and the etiology of age-associated degenerative diseases. The purpose of this study is to examine changes in DNA damage during aging. An oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (8-OHdG), is a proposed biomarker for DNA damaged by oxidative stress. The content of 8-OHdG in nuclear DNA isolated from brain, heart, liver, and kidneys of male Fischer 344 rats of different ages was measured. 8-OHdG can be detected selectively and sensitively at the fmol level by high performance liquid chromatography-electrochemical detection at an applied potential of + 350 mV. The amount of 8-OHdG, expressed as the ratio to deoxyguanosine in nuclear DNA, in heart, liver, and kidney remained steady from 2 to 24 months and then increased progressively. The content of 8-OHdG in the DNA in brain showed no changes from 2 to 27 months, but was significantly higher in 30 month-old rats. There was a significant 2-fold increase in the amount of 8-OHdG in the nuclear DNA of all organs tested in 30 month-old rats as compared to 2-24 month-old rats. These results indicate that the accumulation of 8-OHdG in the DNA of rat organs begins at ages above 24 months.