Reduction of potential for replicative but not unscheduled DNA synthesis in hepatocytes isolated from aged as...

Replicative DNA synthesis of hepatocytes obtained from 2- to 3-month-old and 28- to 30-month-old rats was examined in primary culture under serum-free conditions to clarify whether observed age-related changes in DNA replication depend exclusively on intracellular events, or whether humoral factors are involved. Hepatocyte replicative DNA synthesis of the aged rats was significantly lower (less than one tenth, P less than 0.001) than that of 2- to 3-month-old rats. EGF receptor assays, however, revealed no difference in either number or affinity of the cell surface receptors between hepatocytes from aged as opposed to young rats. Furthermore, sera obtained from aged rats did not demonstrate any inhibitory effect on DNA synthesis of young rat hepatocytes. After treatment with N-hydroxy acetylaminofluorene, N-nitroso-N-methylurea, or 254-nm UV irradiation degree of resultant UDS was similar in hepatocytes from both young and aged animals. Thus, while the results suggest that potential for DNA replication markedly diminishes with age, DNA repair systems are well preserved.