Effects of age and food restriction on oxidative DNA damage and antioxidant enzyme activities in the mouse aorta

In this study, DNA damage in mouse aortic cells was measured using the come t assay. The tail moment of the comet assay in aortic cells obtained from 2 6-month-old mice fed ad libitum (O) was significantly increased as compared to 6-month-old mice fed ad libitum (Y-AL) after the cells were incubated w ith formamidopyrimidine-DNA glycosylase (Fpg), which specifically recognize s oxidized purines, endonuclease III (Endo III), which specifically recogni zes oxidized pyrimidines, or the combination of Endo III and Fpg. The tail moment in aortic cells obtained from 26-month-old mice fed a food-restricte d diet (O-FR) was significantly reduced as compared to O-AL mice after the cells were incubated with the combination of Endo III and Fpg. These result s indicate that oxidative DNA lesions, i.e. the Endo III- and Fpg-sensitive sites, increase with age in mouse aortic cells and that FR attenuates the age-related increase in oxidative DNA damage. To determine if the changes i n oxidative DNA damage in mouse aortic cells are related to the antioxidant status in these cells, we measured the activities of Cu/Zn-superoxide dism utase (SOD), Mn-SOD, extracellular-SOD, catalase and glutathione peroxidase -1 in the mouse aorta, We observed that the activities of all antioxidant e nzymes studied were significantly increased with age and that FR attenuated the age-related increase. These data indicate that the age-related increas e and FR-induced decrease in oxidative DNA damage, i.e. the Endo III- and F pg-sensitive sites, in mouse aortic cells is not due to alteration of the a ntioxidant defense system. (C) 2001 Elsevier Science Ireland Ltd. All right s reserved.