Oxidative damage to DNA is shown to be extensive and could be a major cause of the physiological changes associated with aging and the degenerative diseases related to aging such as cancer. The oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (oh8dG), one of the -20 known oxidative DNA damage products, has been measured in DNA isolated from various organs of Fischer 344 rats of different ages. oh8dG was present in the DNA isolated from all the organs studied: liver, brain, kidney, intestine, and testes. Steady-state levels of oh8dG ranged from 8 to 73 residues per 10' deoxyguanosine residues or 0.2-2.0 x 105 residues per cell. Levels of oh8dG in DNA increased with age in liver, kidney, and intestine but remained unchanged in brain and testes. The urinary excretion of oh8dG, which presumably reflects its repair from DNA by nuclease activity, decreased with age from 481 to 165 pmol per kg of body weight per day for urine obtained from 2-month-and 25-month-old rats, respectively. 8-Hydroxyguanine, the proposed repair product of a glycosylase activity, was also assayed in the urine. We estimate -9 x 104 oxidative hits to DNA per cell per day in the rat. The results suggest that the age-dependent accumulation of oh8dG residues observed in DNA from liver, kidney, and intestine is principally due to the slow loss of DNA nuclease activity; however, an increase in the rate of oxidative DNA damage cannot be ruled out.The biochemical mechanisms of aging are under extensive investigation but remain poorly understood. Endogenous metabolic processes are implicated as important factors in aging by the impressive inverse correlation between life-span and species-specific metabolic rate (1).The damage produced by endogenously produced oxygen radicals has been proposed to be a major contributor to aging and the degenerative diseases associated with it, such as cancer and heart disease (2-7). In vivo, oxygen radicals are mainly produced as by-products of normal metabolism (8) from phagocytic cells (9) and from lipid peroxidation (10). Numerous defense systems protect cellular macromolecules against oxidation; nevertheless, there is a high rate of damage to DNA (11), proteins (12), and lipids (10, 13). The steadystate level of oxidatively modified nucleosides in genomic and mitochondrial DNA in rats (11) and the release of these damage products in human and rodent urine (14-16) have been determined. Oxidative damage to DNA has been estimated as 104 hits per cell per day in humans and 1 order of magnitude higher in rodents (7,14,15).Some evidence suggests that an increased production of reactive oxygen species and/or a decreased efficiency of antioxidant defense systems is associated with aging (17,18). Endogenous oxidative damage to lipids (19) and proteins (12) has been reported to increase with age. Damage to DNA has been reported to increase with age in rats fed diets deficient in vitamin E, but not in rats fed vitamin E-sufficient diets (20).The purpose of this study was to evaluate endogenous oxidative damage to DNA as...

Consuming polyphenols is associated with benefits to cardiometabolic health and brain function, which are driven by their complex interrelationship with the gut microbiome, their bioactive metabolites, and other phytochemicals.

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