Gender difference in glutathione metabolism during aging in mice.

Oxidative damage of the macromolecules increases with age and has been suggested to contribute importantly to the aging process and the pathogenesis of many age-related diseases. However, what causes such an increase in the oxidative damage of the macromolecules and whether male and female have the same susceptibility are not clear. In this study, we demonstrated for the first time that although the concentrations of GSH were similar between young male and female mice in most tissues examined and GSH content declined with age in both genders, male mice seemed to experience more dramatic age-associated change in GSH content than did female mice in many tissues. The age-related decline in the GSH content in both male and female mice was also associated with a decrease in the amounts of glutamate cysteine ligase (GCL) mRNAs and proteins as we have reported previously in male rats, further suggesting an important role of GCL in maintaining GSH homeostasis during the aging process. The results from this study may reveal an important basis underlying the gender-associated differences in the longevity and the susceptibility to certain age-related diseases, and also further suggest that the decreased synthesis, which is mainly due to the down regulation of GCL gene expression, may be responsible for the age-associated decline in GSH content.