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

Abstract

Accelerated changes in the DNA ploidy associated with in vitro aging were examined in fibroblast-like cells isolated from the dorsal dermis of newborn SAMP11 (accelerated senescence-prone, short-lived) mice, and were compared to changes observed in cell lines from SAMR1 (accelerated senescence-resistant, long-lived) mice. Flow cytometric analysis of the DNA content in confluent cells and chromosome analysis in mitoses 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 decreased as the crisis ensued, then increased. Although these changes were observed in the cell lines from both strains of mice, the changes occurred more rapidly and at earlier population doublings in the cell lines from the SAMP11 mice. These results suggest that the cell lines from SAMP11 mice might have higher susceptibility to factors that cause polyploidization, including oxidative stress.