Oxidative damage to proteins is implicated in aging and other age-related diseases. Because the level of damaged proteins reflects balance between prooxidant, antioxidant, repair, and degradation of damaged proteins, we examined the relations between aging and levels of oxidized proteins (carbonyl content), antioxidant enzymes, oxidized (GSSG) and reduced (GSH) forms of glutathione, and the capacity to undergo oxidative stress (hydrogen peroxide)-induced programmed cell death (apoptosis) in cultured fibroblasts from human individuals of different ages over the range of 2 to 76 years and also in other cell types (A431, Hela, NIH3T3, Jurket). It was found that aging is associated with an increase in protein carbonyl content, a decrease of activity in various antioxidant enzymes (catalase, GSH reductase, GSH peroxidase, GSH-s-transferase, glucose-6-phosphate dehydrogenase), but an increase of activity in superoxide dismutase, a decrease in total glutathione and an increase in GSSG. The apoptotic activities of fibroblasts did not change with age. However, the apoptotic responses of A431, Hela, NIH3T3, and Jurkat cells varied and exhibited a concentration-dependent biphasic response to hydrogen peroxide concentration, suggesting the occurrence of both reversible and irreversible inactivation of caspase 3 could be involved. The reversible inactivation might be due to the oxidation of essential cysteine or methionine residues in caspases and the irreversible inactivation might couple with protein degradation via specific pathways. These possibilities are currently under investigation.
