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Updated: May 22, 2026

Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
The oxidative DNA lesions 8,5'-cyclopurines accumulate with aging in a tissue-specific manner
Jin Wang1, Cheryl L Clauson, Paul D Robbins
1Department of Chemistry, University of California, Riverside, CA 92521-0403, USA.
Abstract:
Accumulation of DNA damage is implicated in aging. This is supported by the fact that inherited defects in DNA repair can cause accelerated aging of tissues. However, clear-cut evidence for DNA damage accumulation in old age is lacking. Numerous studies report measurement of DNA damage in nuclear and mitochondrial DNA from tissues of young and old organisms, with variable outcomes. Variability results from genetic differences between specimens or the instability of some DNA lesions. To control these variables and test the hypothesis that elderly organisms have more oxidative DNA damage than young organisms, we measured 8,5'-cyclopurine-2'-deoxynucleosides (cPu), which are relatively stable, in tissues of young and old wild-type and congenic progeroid mice. We found that cPu accumulate spontaneously in the nuclear DNA of wild-type mice with age and to a greater extent in DNA repair-deficient progeroid mice, with a similar tissue-specific pattern (liver > kidney > brain). These data, generated under conditions where genetic and environmental variables are controlled, provide strong evidence that DNA repair mechanisms are inadequate to clear endogenous lesions over the lifespan of mammals. The similar, although exaggerated, results obtained from progeroid, DNA repair-deficient mice and old normal mice support the conclusion that DNA damage accumulates with, and likely contributes to, aging.
Insights
Aging is linked to DNA damage accumulation. This study shows oxidative DNA damage, specifically 8,5'-cyclopurine-2'-deoxynucleosides (cPu), increases with age in mice, suggesting DNA repair is insufficient over a lifespan.
Area of Science:
- Molecular Biology
- Genetics
- Gerontology
Background:
- DNA damage accumulation is a proposed mechanism driving the aging process.
- Inherited DNA repair deficiencies are known to cause premature aging syndromes.
- Direct evidence for age-related DNA damage accumulation in mammals has been limited and variable.
Purpose of the Study:
- To investigate the accumulation of oxidative DNA damage with age in mammals.
- To test the hypothesis that elderly organisms accumulate more oxidative DNA damage than younger organisms.
- To assess the role of DNA repair mechanisms in preventing age-related DNA damage.
Main Methods:
- Measurement of 8,5 -cyclopurine-2 -deoxynucleosides (cPu), a stable marker of oxidative DNA damage.
- Analysis in tissues (liver, kidney, brain) of young and old wild-type mice.
- Comparison with congenic progeroid mice with known DNA repair deficiencies.
Main Results:
- Spontaneous accumulation of cPu in nuclear DNA was observed in wild-type mice with increasing age.
- CPu levels were significantly higher in DNA repair-deficient progeroid mice compared to age-matched wild-type mice.
- A consistent tissue-specific pattern of cPu accumulation (liver > kidney > brain) was noted in both mouse models.
Conclusions:
- Age-related accumulation of endogenous oxidative DNA damage occurs in mammals.
- Existing DNA repair mechanisms appear inadequate to fully clear these lesions throughout the lifespan.
- DNA damage accumulation likely contributes to the aging process.
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