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Aging and oxidatively damaged nuclear DNA in animal organs
Authors:Peter Møller  Mille Løhr  Janne K Folkmann  Lone Mikkelsen  Steffen Loft
Institution:1. Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, Jiangsu, China;2. Department of Endocrinology, Affiliated Drum Tower Hospital, Medical College of Nanjing University, Nanjing, Jiangsu, China;3. Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, Jiangsu, China;4. The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, China
Abstract:Oxidative stress is considered to contribute to aging and is associated with the generation of oxidatively damaged DNA, including 8-oxo-7,8-dihydroguanine. We have identified 69 studies that have measured the level of oxidatively damaged DNA in organs of animals at various ages. In general, organs with limited cell proliferation, i.e., liver, kidney, brain, heart, pancreas, and muscle, tended to show accumulation of DNA damage with age, whereas organs with highly proliferating cells, such as intestine, spleen, and testis, showed more equivocal or no effect of age. A restricted analysis of studies reporting a baseline level of damaged DNA that was fewer than 5 lesions/106 dG showed that 21 of 29 studies reported age-associated accumulation of DNA damage. The standardized mean difference in oxidatively damaged DNA between the oldest and the youngest age groups was 1.49 (95% CI 1.03–1.95). There was no difference between age span, number of tested organs, statistical power, sex, strain, or breeding between the studies showing positive and null effects. Citation and publication bias seems to be a problem in the overall dataset, whereas it is less pronounced in the restricted dataset. There is compelling evidence for aging-associated accumulation of oxidatively damaged DNA in organs with limited cell proliferation.
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