Age-Related Shortening of Poly(A) Tail of Albumin mRNA

Abstract

To determine the molecular mechanisms of age-related changes in hepatic albumin gene expression, male Fisher 344 rats at 4, 12, and 24 months of age were studied. The hepatic albumin content was modestly increased by 20% and plasma albumin concentration was not altered with age. There were no age-related changes in albumin mRNA content of the liver. Thein vivosynthetic rate of albumin as measured with [14C]leucin incorporation in 4-month-old rats (350 ± 24.5 cpm) was not significantly different from that in 24-month-old rats (393 ± 30.3 cpm). However,in vitrotranslational efficiency of albumin mRNA from 24-month-old rats was only 49% of that in 4-month-old rats. This was correlated with shortening of the poly(A) tail of albumin mRNA from approximately 300–450 bases in 4-month-old rats to only 50–100 bases in 24-month-old rats. The reduced albumin mRNA translational efficiencyin vitroalong with shortening of the poly(A) tail with age is probably an adaptive response since hepatic albumin content was increased and plasma albumin concentrations were not altered with age. The age-related shortening of the poly(A) tail is yet another mechanism of age-related alterations in the expression of specific genes where the changes seen with age are mostly translational.Key Words:aging; albumin synthesis; translational control; poly(A) tail.