Oxidants are a major contributor to aging.
Very high level oxidative damage to DNA occurs during normal metabolism. In each rat cell the steady-state level of this damage is estimated to be about 10(6) oxidative adducts, and about 10(5) new adducts are formed daily. This endogenous DNA damage appears to be a major contributor to aging and to the degenerative diseases associated with aging such as cancer. The oxidative damage rate in mammalian species with a high metabolic rate, short life span, and high age-specific cancer rate such as rats is much higher than the rate in humans, long-lived mammals with a lower metabolic rate and a lower age-specific cancer rate. It is argued that deficiency of micronutrients that protect against oxidative DNA damage is a major contributor to human cancer. Epidemiological studies, a large body of experimental evidence, and theoretical work on the mechanisms of carcinogenesis point to mitogenesis as a major contributor to cancer. Dividing cells compared to nondividing cells are at an enormously increased risk for mutations in part due to the conversion of DNA adducts to mutations. Mitogenesis also increases the probability of gene amplification and loss of 5-methylcytosine. Dietary interventions that lower mitogenesis, such as calorie restriction, decrease the incidence of cancer.
Ames
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BN
Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720.
Shigenaga
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MK
D000375:Aging; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D004249:DNA Damage; D004032:Diet; D002149:Energy Intake; D006801:Humans; D008938:Mitosis; D016877:Oxidants / Q000633:toxicity*
D016587:Antimutagenic Agents; D000975:Antioxidants; D016877:Oxidants