Effects of age and dietary restriction on oxidative DNA damage, antioxidant protection and DNA repair in rats.
BACKGROUND
Experimentally imposed dietary restriction is known to extend the lifespan of rodents, perhaps by slowing the accumulation of oxidative damage that is thought to be one of the causes of aging.


OBJECTIVE
We examined the effects of restricted total food intake, and protein and calorie restriction, on DNA oxidation and related biomarkers in rats.


METHODS
From 1 to 17 months, rats in group 1 received normal diet ad libitum. Group 2 received 70% of the quantity consumed by the first group. Group 3 had the same quantity as group 2, but with a reduction in protein (from 18% to 10% of the diet by weight), and group 4 were further restricted with a 30% decrease in calories. Lymphocytes were isolated from blood samples taken every two months. DNA breaks, oxidised pyrimidines, resistance to H2O2-induced damage, and strand break repair were measured with the comet assay. Organs were isolated from rats killed at 17 months, with 1 month-old rats for comparison; DNA oxidation and antioxidant enzyme activities were measured.


RESULTS
DNA breaks in lymphocytes increased from 1 to 3 months but thereafter declined with age, except in ad libitum fed rats. Oxidised pyrimidines did not change significantly. Resistance to H2O2-induced damage was least at 3 months, and increased with age. Repair of DNA strand breaks was efficient at all ages. Diet had little effect on these endpoints. Diet had no influence on 8-oxo-7.8-dihydroguanine levels in DNA from liver, testis and brain of 17 month old rats. Combining data from all four groups, the levels in brain and liver were significantly higher at 17 months compared with 1 month. Antioxidant enzyme activities tended to increase between 1 and 17 months; effects of diet were not so consistent.


CONCLUSIONS
While DNA damage shows a modest increase with age in some organs, antioxidant status and DNA strand break repair do not decline with age. Restricted diets (including protein and calorie restriction) have no effect on any of these markers of genetic stability.
Rowett Research Institute, Greenburn Road, Aberdeen AB21 9SB, Scotland.
C M
CM
Gedik
G
G
Grant
P C
PC
Morrice
S G
SG
Wood
A R
AR
Collins
D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000502:physiology*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D005508:Food Deprivation / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D010084:Oxidation-Reduction; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms
D000975:Antioxidants; D006861:Hydrogen Peroxide