Does oxidative damage to DNA increase with age?
The levels of 8-oxo-2-deoxyguanosine (oxo8dG) in DNA isolated from tissues of rodents (male F344 rats, male B6D2F1 mice, male C57BL/6 mice, and female C57BL/6 mice) of various ages were measured using sodium iodide to prevent oxidative damage to DNA during DNA isolation. Oxo8dG was measured in nuclear DNA (nDNA) isolated from liver, heart, brain, kidney, skeletal muscle, and spleen and in mitochondrial DNA (mtDNA) isolated from liver. We observed a significant increase in oxo8dG levels in nDNA with age in all tissues and strains of rodents studied. The age-related increase in oxo8dG in nDNA from old mice was shown not to the result of the tissue's reduced ability to remove the oxo8dG lesion. Rather, the increase in oxo8dG levels appears to arise from an age-related increase in the sensitivity of these tissues to oxidative stress. We also observed an age-related increase in oxo8dG in mtDNA isolated from the livers of the rats and mice. Dietary restriction, which is known to retard aging and increase the lifespan of rodents, was shown to significantly reduce the age-related accumulation of oxo8dG levels in nDNA in all tissues of male B6D23F1 mice and in most tissues of male F344 rats. Our study also showed that dietary restriction prevented the age-related increase in oxo8dG levels in mtDNA isolated from the livers of both rats and mice.
Hamilton
M L
ML
Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Van Remmen
H
H
Drake
J A
JA
Yang
H
H
Guo
Z M
ZM
Kewitt
K
K
Walter
C A
CA
Richardson
A
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004032:Diet; D005260:Female; D005508:Food Deprivation; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344; D012974:Sodium Iodide; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000378:metabolism; D014018:Tissue Distribution
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D012974:Sodium Iodide; D003849:Deoxyguanosine