The importance of antioxidant enzymes in cellular aging and degeneration.

Aerobic cells contain various amounts of the three main antioxidant enzymes: superoxide dismutase (SOD), catalase and GSH peroxidase. These three enzymes are necessary for cell survival since inhibition of their activity leads to the arrest of cell mitosis and to cell death. Amongst them, GSH peroxidase was shown to be more efficient than catalase and much more than SOD. This result was obtained by comparing the cell protection against oxidative stress after their microinjection in the cytoplasm. With age, the level of these antioxidant enzymes does not change in several experimental models, so that it is not possible to explain the aging process by a lack of protection due to a decrease in the activity of these three enzymes. However, tissues and cells are more susceptible to free radical attacks with age. In order to understand the importance of free radicals in this process, we have to distinguish between their respective effects on cell mitosis, cell death and cell aging. The effects on mitosis and cell death are well described, and the results clearly show a threshold of response which is determined by the antioxidant content of the cell. There is now evidence that short free radical stresses can also speed up the aging of in vitro cultured human fibroblasts. However, such effects are not typical of free radicals but are also obtained with many other deleterious substances so that free radicals have to be considered as one amongst other factors responsible for influencing the evolution of a cell to an older stage or to cell death. The lowering of the general metabolism and of the free energy in old cells are probably the main factors responsible for the increased susceptibility of these cells to stresses such as oxidative stresses.