The oxidative DNA lesions 8,5′-cyclopurines accumulate with aging in a tissue-specific manner
Open accessAbstract
Summary: 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.
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Ercc1 / D mice accumulate oxidative DNA damage faster than wild-type mice.
“accumulate oxidative DNAdamagefasterthanwild-typemice”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Wang et al., 2012
The Abstract (page not provided) reports greater accumulation of oxidative cPu lesions in Ercc1−/Δ mice and a faster increase in their kidneys from 10 to 21 weeks. The claim is too broad: the increase was similar to wild-type mice in liver, while cPu levels decreased with age in Ercc1−/Δ brains. (LLM, conf=0.87)
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Self-citation
- Authors
- Wang, J., Clauson, C. L., Robbins, P. D., Niedernhofer, L. J., & Wang, Y.
- Affiliations
- University of California, Riverside (US)
- University of Pittsburgh (US)
- Corresponding author
- Wang, Yinsheng
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2012-05-22
- Volume
- 11
- Issue
- 4
- Pages
- 714-716
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3399950
- OpenAlex
- W1554622477
- Cited by
- 142
- References
- 16
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 15 · 2020: 7 · 2019: 15 · 2018: 9 · 2017: 9 · 2016: 7 · 2015: 14 · 2014: 11 · 2013: 20 · 2012: 6
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P30AG024827)
- National Cancer Institute (R01CA101864, P30CA047904)
- National Institute of Environmental Health Sciences (R01ES016114)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- oxidative DNA damage, aging, DNA repair deficiency, progeroid mice, tissue-specific accumulation, nuclear DNA, mitochondrial DNA
- MeSH terms
- Aging, Animals, Brain, DNA Damage, DNA Repair, DNA-Binding Proteins, Endonucleases, Female, Kidney, Liver, Male, Purines, Mice, Knockout, Aging, Premature, Mice, Congenic, Mice
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