Aging is associated with reduced liver regeneration and diminished thymidine kinase mRNA content and enzyme activity...

We studied the effect of aging on rat liver regeneration. We compared the time course of total hepatic mass, DNA and RNA accumulation, and thymidine kinase (TK) messenger RNA (mRNA) content and enzyme activity, after two-thirds partial hepatectomy in 6-week-old (young adult) and 1-year-old rats. Whereas 6-week-old rats had completely regenerated all liver mass, DNA, and RNA by 7 days, the regenerating 1-year-old rat livers at 7 days contained only 60% to 70% of the mass, DNA, and RNA in the normal 1-year-old rat liver. However, rates of tissue regeneration during this time were very similar in both ages. At 28 days the weight and RNA content of the 1-year-old rat livers were 93% of normal, but total DNA was still reduced, at 78% of normal. In the younger rats TK mRNA content and enzyme activity increased substantially after partial hepatectomy and were observed to peak at 24 hours. In the 1-year-old rats TK mRNA was less abundant in normal liver and the peak level observed was lower and delayed until 48 hours. Nonetheless, the incremental increase from baseline to peak was greater in the 1-year-old than in the 6-week-old rats. In contrast to the mRNA, TK activity peaked at 24 hours, but at substantially lower levels than in the 6-week-old rats. Rates of disappearance of TK mRNA and enzyme activity after peak levels were not significantly different by age.(ABSTRACT TRUNCATED AT 250 WORDS)