ACCELERATED AGING OF DERMAL FIBROBLAST-LIKE CELLS FROM THE SENESCENCE-ACCELERATED MOUSE (SAM) - ACCELERATION OF CHANGES IN DNA-PLOIDY ASSOCIATED WITH IN-VITRO CELLULAR AGING

Accelerated changes in the DNA ploidy associated with in vitro aging w ere examined in fibroblast-like cells isolated from the dorsal dermis of newborn SAMP11 (accelerated senescence-prone, short-lived) mice, an d were compared to changes observed ill cell lines from SAMR1 (acceler ated senescence-resistant, long-lived) mice. Flow cytometric analysis of the DNA content in confluent cells and chromosome analysis in mitos es revealed that the diploid cells were being replaced with tetraploid cells until a growth crisis; thereafter, hypotetraploid cells became predominant, accompanied by immortalization. The number of mitoses dec reased as the crisis ensued, then increased. Although these changes we re observed in the cell lines from both strains of mice, the changes o ccurred more rapidly and at earlier population doublings in the cell l ines from the SAMP11 mice. These results suggest that the cell lines f rom SAMP11 mice might have higher susceptibility to factors that cause polyploidization, including oxidative stress.