Natural and conditional ageing of mouse fibroblasts: genetic vs. epigenetic control.

Mouse embryonic fibroblasts were fused with a spontaneously immortalized mouse fibroblast cell line and a large number of heterogeneous hybrid populations were obtained. These showed variations with respect to their chromosomal number as well as in vitro life span but none acquired immortal phenotype. Apart from demonstrating the dominant nature of senescence over immortalization in mouse system, we also provide the first report on the analysis of genomic DNA methylation during in vitro passaging of parental and hybrid cell populations representing the normal and conditional ageing, respectively. Since no random decline in DNA methylation could be detected in any of the cases, our results suggest that it is unlikely that mortality of cells in culture is the outcome of random loss of epigenetic control imposed by 5-methyldeoxycytidine at CpG sites in the genome.