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.

Aging Cell
|April 26, 2012
PubMed

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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