Age-related changes in apolipoprotein A-I expression

Abstract

To determine the age-related changes in apolipoprotein A-I (ApoA 1) expression, male Fischer 344 rats at 4 (young), 12 (intermediate age), and 24–26 (aged) months of age were studied. Immunoblot analysis of plasma proteins indicated that 26-month-old rats (1.79 ± 0.16 mg/ml) and 12-month-old rats (2.23 ± 0.11 mg/ml) have significantly higher plasma ApoA 1 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 hepatic ApoA 1 mRNA in aged rats was also reflected in the increased translation of ApoA 1 mRNA in vitro. Reduced mRNA turnover may account for the increased hepatic ApoA 1 mRNA content in 26-month-old rats, since the rate of ApoA 1 gene transcription as measured with nuclear run off assays was significantly reduced with age. The ApoA 1 synthesis in vivo, as measured by [ 14C]leucine incorporation at 30 min, was reduced 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 protein is probably secondary to reduced metabolic clearance rate of ApoA 1 protein or is the result of increased intestinal synthesis of ApoA 1.