Effect of age and dietary restriction on the expression of alpha 2u-globulin

The effect of aging on the expression of alpha 2u-globulin was studied in liver tissue from 6-30-month-old male Fischer F344 rats. The synthesis of alpha 2u-globulin by suspensions of isolated hepatocytes decreased 90% between 6 and 22 months of age. The levels of alpha 2u-globulin mRNA and the transcription of alpha 2u-globulin genes by isolated liver nuclei decreased 80-85% between 5 and 24 months of age. Because alpha 2u-globulin has been suggested to be a "senescence marker protein," the expression of alpha 2u-globulin was measured in rats fed a diet restricted in calories. This dietary restriction procedure has been shown to increase significantly the longevity of rodents. The expression of alpha 2u-globulin was compared in liver tissue from 18-month-old rats fed ad libitum and a restricted diet (40% restriction of total calories). The synthesis, mRNA levels, and transcription of alpha 2u-globulin were 1.8-3-fold higher for liver tissue from restricted rats compared to liver tissue from rats fed ad libitum. Therefore, dietary restriction alters the age-related change in the expression of alpha 2u-globulin. Our results demonstrate that the changes in alpha 2u-globulin expression that arise during aging or dietary restriction are regulated at the level of transcription.