AGE-RELATED-CHANGES IN APOLIPOPROTEIN-A-I EXPRESSION

To determine the age-related changes in apolipoprotein A-I (ApoA(1)) e xpression, male Fischer 344 rats at 4 (young), 12(intermediate age), a nd 24-26 (aged) months of age were studied. Immunoblot analysis of pla sma proteins indicated that 26-month-old rats (1.79 +/- 0.16 mg/ml) an d 12-month-old rats (2.23 +/- 0.11 mg/ml) have significantly higher pl asma ApoA, concentrations compared to 4-month-old rats (1.14+/-0.15 mg /ml) P< 0.001. Hepatic ApoA(1) mRNA was approx. 2-fold higher in aged rats compared to 12-month-old and 4-month-old rats. This increase in h epatic ApoA(1) mRNA in aged rats was also reflected in the increased t ranslation of ApoA(1) mRNA in vitro. Reduced mRNA turnover may account for the increased hepatic ApoA, mRNA content in 26-month-old rats, si nce the rate of ApoA(1) gene transcription as measured with nuclear ru n off assays was significantly reduced with age. The ApoA(1) synthesis in vivo, as measured by [C-14]leucine incorporation at 30 min, was re duced in aged rats compared to young rats (170.5 +/- 10.2 vs. 253.9 +/ - 7.7 cpm per liver) P < 0.001 probably as a result of changes related to cellular metabolism rather than an alteration inherent to the ApoA (1) mRNA translatability. The age-related increase in plasma ApoA(1) p rotein is probably secondary to reduced metabolic clearance rate of Ap oA(1) protein or is the result of increased intestinal synthesis of Ap oA(1).