S. S. Akimov

Reverse transcriptase inhibitors suppress telomerase function and induce senescence-like processes in cultured mouse fibroblasts

Spontaneous transformation of mouse embryonic fibroblasts in the presence of the reverse transcriptase inhibitors azidothymidine and carbovir led to the formation of telomerase‐free clones. After prolonged cultivation of fibroblasts in the presence of carbovir, resistant cells with a very high level of telomerase activity were obtained. Azidothymidine and carbovir, but not dideoxycytidine, induced senescence‐like processes in cultures of immortal mouse fibroblasts. After long‐term incubation, cell proliferation gradually decreased, their morphology becoming similar to that of the senescent ones. The process was reversible: after inhibitor removal, the cells, including the giant ones, entered mitoses. All these data suggest that reverse transcriptase inhibitors block telomerase function in mouse cells.

Senescent accelerated mouse (SAM): A model that binds in vivo and in vitro aging

It is known that the longevity of senescence accelerated mouse (SAM) is significantly reduced. We intended to check the relationship of the SAM shortened longevity with some characteristics of their cells in culture. Investigations of lifespans of SAM embryo fibroblasts, survival of senescent nondividing cells, endogenous β-galactosidase activity, telomerase activity, and telomere length were conducted. There is correlation of longevity of SAMP1 (senescence prone strain), SAMR1 (accelerated senescence resistant strain), and CBA mice with proliferative lifespans of their embryo fibroblasts in vitro as well as with the survival time of nondividing senesced embryo fibroblasts. The premature senescence of SAMP1 and SAMR1 fibroblasts is associated with accelerated accumulation of the β-galactosidase-positive cells. Terminal restriction fragments of chromosomes of SAMP1 are more heterogeneous than SAMR1 ones. There is relatively high telomerase activity (in comparison with CBA mice) in SAM embryos and cell cult...

Proliferative Senescence of Embryo Fibroblasts of Japanese Senescence Accelerated Mice is Accompanied by Parallel Decreasing of the Response to Various Growth Factors

The Japanese senescence accelerated mice (SAM) are a group of the low-longevity mouse lines and represent a new convenient model for studying the senescence process. We studied the proliferation of embryo fibroblasts of SAMP1 and SAMR1 mouse lines. It was shown that fibroblasts of the shortest longevity line SAMP1 have a markedly decreased proliferative potential of the mean 8.7 population doublings, whereas fibroblasts of a relatively high-longevity line SAMR1 have an average proliferative potential of 12.3 doublings. The fibroblast senescence in both lines is accompanied by simultaneous lowering of the cell proliferative response to the blood serum, epidermal, fibroblast, and platelet-derived growth factors. At initial stages of the cell culture growth, lines SAMP1 and SAMR1 exhibit the same reactions to growth factors, but already beginning from the fifth doubling, the SAMP1 cell response is sharply decreased as compared with SAMR1. Lowering of the proliferative reaction is accompanied by decreased phosphorylation of tyrosine in the cell proteins responsible for the mitogenic reaction. Thus, the parallel decrease in the proliferative response to different growth factors during fibroblast senescence is most likely due to the emergence of a regulatory block at common stages of the mitogenic signal transduction.