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Non-linear accumulation of 8-hydroxy-2'-deoxyguanosine, a marker of oxidized DNA damage, during aging
1Tokyo Metropolitan Institute of Gerontology, Japan. kaneko@center.tmig.or.jp
Abstract:
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.
Insights
DNA damage, measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG), increases in rat organs after 24 months of age. This finding links oxidative stress biomarkers to aging and potential age-associated diseases.
Area of Science:
- Gerontology
- Molecular Biology
- Biochemistry
Background:
- DNA damage is implicated in aging and age-related diseases.
- Oxidative stress is a key factor contributing to DNA damage.
- 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a biomarker for oxidative DNA damage.
Purpose of the Study:
- To investigate the changes in DNA damage during the aging process.
- To quantify 8-OHdG levels in various rat organs across different ages.
Main Methods:
- Nuclear DNA was isolated from the brain, heart, liver, and kidneys of male Fischer 344 rats of varying ages.
- High-performance liquid chromatography with electrochemical detection was used to measure 8-OHdG content.
- 8-OHdG levels were quantified relative to deoxyguanosine.
Main Results:
- 8-OHdG levels in heart, liver, and kidney DNA remained stable from 2 to 24 months, then progressively increased.
- Brain DNA showed no change in 8-OHdG until 27 months, with a significant increase at 30 months.
- A twofold increase in 8-OHdG was observed in all tested organs of 30-month-old rats compared to younger rats.
Conclusions:
- DNA damage, specifically 8-OHdG accumulation, begins in rat organs after 24 months of age.
- These findings suggest a link between aging, oxidative stress, and DNA damage accumulation in vital organs.