G. Barja

Reactive oxygen species (ROS), continuously generated in the mitochondria of healthy post-mitotic tissues, are thought to contribute significantly to aging. Studies from our laboratory dealing with the relationship between oxidative stress and aging will be presented. ROS can damage cellular lipids, proteins and, most importantly, DNA. Although antioxidants help to control oxidative stress in cells in general, they do not increase the maximum life span of mammals and their levels are lower in long-lived than in short-lived animals. 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 localized at complex I and the mechanism involved is related to the degree of electronic reduction of the complex I ROS generator. Interestingly, the same site and mechanism have been found when comparing a long-lived with a short-lived animal species. Lower levels of oxidative damage in mtDNA have also been recently found in long-lived Ames dwarf mice in comparison with wild type controls. Thus, the results obtained in three different mammalian models of extended longevity support the idea that the rate of mitochondrial ROS generation and oxidative attack to mtDNA is involved in determining aging rate: long- versus short-lived species, caloric restricted rodents and Ames dwarf mice.

Keywords (Optional): 
oxygen radicals
DNA damage
caloric restriction
Ames dwarf mice