Aging in vertebrates, and the effect of caloric restriction: a mitochondrial free radical production-DNA damage mechanism?
Oxygen is toxic to aerobic animals because it is univalently reduced inside cells to oxygen free radicals. Studies dealing with the relationship between oxidative stress and aging in different vertebrate species and in caloric-restricted rodents are discussed in this review. Healthy tissues mainly produce reactive oxygen species (ROS) at mitochondria. These ROS can damage cellular lipids, proteins and, most importantly, DNA. Although antioxidants help to control this oxidative stress in cells in general, they do not decrease the rate of aging, because their concentrations are lower in long- than in short-lived animals and because increasing antioxidant levels does not increase vertebrate maximum longevity. However, long-lived homeothermic vertebrates consistently have lower rates of mitochondrial ROS production and lower levels of steady-state oxidative damage in their mitochondrial DNA than short-lived ones. Caloric-restricted rodents also show lower levels of these two key parameters than controls fed ad libitum. The decrease in mitochondrial ROS generation of the restricted animals has been recently localized at complex I and the mechanism involved is related to the degree of electronic reduction of the complex I ROS generator. Strikingly, the same site and mechanism have been found when comparing a long- with a short-lived animal species. It is suggested that a low rate of mitochondrial ROS generation extends lifespan both in long-lived and in caloric-restricted animals by determining the rate of oxidative attack and accumulation of somatic mutations in mitochondrial DNA.
Barja
Gustavo
G
Department of Animal Biology-II (Animal Physiology), Faculty of Biology, Complutense University, Madrid 28040, Spain.
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004249:DNA Damage; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D005609:Free Radicals / Q000378:metabolism; D008136:Longevity / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010101:Oxygen Consumption; D017382:Reactive Oxygen Species / Q000378:metabolism; D014714:Vertebrates / Q000235:genetics / Q000502:physiology*
D005609:Free Radicals; D017382:Reactive Oxygen Species