EFFECT OF AGE ON THE EXPRESSION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE IN RAT-LIVER

The effect of age on the expression of phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) was studied using hepatocytes isolated from 6-, 15-, and 26-mo-old-male Fischer 344 rats fasted for 12 h. The activity of PEPCK in hepatocyte extracts decreased 40-50% (P < 0.05) between 6 and 26 mo of age. The age-related decrease in PEPCK activity was paralleled by a similar decrease (P < 0.05) in the level of PEPCK mRNA. Thus the decrease in PEPCK activity appears to arise from a decrease in level of the PEPCK transcript available for translation. The stability, i.e., half-life of PEPCK mRNA in hepatocytes isolated from 6- and 26-mo-old rats was similar; however, the nuclear transcription of PEPCK by hepatocytes isolated from 26-mo-old rats was 44% lower (P < 0.05) than the nuclear transcription of PEPCK by hepatocytes isolated from 6-mo-old rats. Thus the age-related decline in PEPCK mRNA levels in the liver of fasted rats appears to arise from a decrease in the transcription of PEPCK. A significant decrease (P < 0.05) in the activity and mRNA level of PEPCK also was observed with age in kidney tissue isolated from rats fasted for 12 h.