Calorie restriction modulates redox-sensitive AP-1 during the aging process.

Oxidative stress is claimed to be a major cause of aging. Recent data suggest that calorie restriction (CR) prolongs life span by its ability to retard aging, possibly by regulating the intracellular redox status through its antioxidative actions. Currently, there is little information showing the influences of age and CR on the redox-sensitive transcription factor activator protein-1 (AP-1). In the present study, we investigated how age affects the status of AP-1 and whether CR modulates the age effect. For our study, we used the kidney from male Fischer 344 rats, ages 6, 12, 18, and 24 months fed ad libitum (AL) or a CR diet. Results from our study showed that AP-1 binding activity markedly increases with age, while CR keeps this activity at the level of 6-month-old rats. We found that c-Jun and c-Fos protein levels increase during aging, and that aging induces phosphorylation of c-Jun, which might enhance AP-1 transcriptional activity. For CR's action, we found that in the nucleus of aged rats, AP-1 activation was blunted by decreasing c-Jun and c-Fos levels and inhibiting c-Jun protein phosphorylation. Results also indicated that matrix metalloproteinase-13 and heme oxygenase-1, which have an AP-1 binding site in their promoter regions, have a similar tendency toward AP-1 binding activity. Based on the data of these findings, we concluded that AP-1 activity increases in rat kidney with age and that CR reduces AP-1 activity.