Aging and oxidatively damaged nuclear DNA in animal organs.
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/10(6) 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.
Møller
Peter
P
Section of Environmental Health, Department of Public Health, University of Copenhagen, DK-1014 Copenhagen K, Denmark. pemo@sund.ku.dk
Løhr
Mille
M
Folkmann
Janne K
JK
Mikkelsen
Lone
L
Loft
Steffen
S
D000375:Aging; D000825:Animal Structures / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D004249:DNA Damage; D019992:Databases as Topic; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D017594:Publication Bias
C024829:8-hydroxyguanine; D006147:Guanine