Aging alters ornithine decarboxylase and decreases polyamines in regenerating rat liver but putrescine replacement...

Aging decreases rat liver regeneration. We (1) compared the expression of ornithine decarboxylase (ODC), a critical enzyme for liver regeneration, and polyamine levels in regenerating liver of 6-week-old and 1-year-old rats and (2) evaluated the effect of exogenous putrescine supplementation on liver regeneration in 1-year-old rats. ODC messenger ribonucleic acid (mRNA) transcript sizes were the same in rats of both ages. ODC mRNA content and enzyme activity were higher in the younger rats; however, magnitudes of increase after partial hepatectomy were greater in the older rats. From peak levels, the rate of decline of the mRNA was slower in the older rats, but enzyme activity declined at the same rate in both ages. ODC apoenzyme content was significantly less in normal liver tissue from 1-year-old rats, but there was little change after partial hepatectomy in rats of either age. No change in ODC transcriptional activity was found. Hepatic putrescine levels were lower in 48 hours regenerating liver tissue from 1-year-old rats. To determine whether supplemental putrescine would increase liver regeneration in 1-year-old rats, putrescine (600 mumol/kg IP every 4 hours) was administered beginning 4 days before or at the time of partial hepatectomy. This raised polyamine levels and decreased ODC activity significantly, but there was no change in regenerating liver weight, total DNA and RNA content, and tritiated thymidine incorporation at 48 hours. These results indicate that ODC expression is different and polyamine levels are lower in 1-year-old rats than in 6-week-old rats. However, putrescine supplementation that is sufficient to decrease ODC activity has no apparent effect on regeneration.