Age related decline in the expression of proliferating cell nuclear antigen in human diploid fibroblasts

Proliferating cell nuclear antigen mRNA and protein levels were determined in human diploid fibroblasts of different in vitro ages as they progressed through the cell cycle. Cells were analyzed at G0; at various stages of G1, including the G1/S interface; and during S. At all in vitro ages, PCNA message levels were low to undetectable at G0, were evident 8 to 12 h following entrance into G1, peaked at G1/S and declined during S phase. Message levels were 2-3-fold lower in older populations at all stages of the cell cycle tested. PCNA protein increased from G0 through S phase in both age groups with 2-3-fold less being found in older cells. The decline in PCNA mRNA in older populations was not the result of changes in mRNA turnover or transcription. The results suggest that the reduction in PCNA expression is due to an age related alteration in a post-transcriptional regulatory function. The decline in the expression of the PCNA gene would contribute to the inability of older cells to initiate replicative DNA synthesis.