Oxygen Radicals and Aging
G. Barja
Department of Animal Biology II (Animal Physiology), Faculty of Biology, Complutense University, Madrid 28040, Spain.
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.
Key words:
aging, oxygen radicals, DNA damage, caloric restriction, Ames dwarf mice
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