Cellular senescence in telomerase-expressing Syrian hamster embryo cells

We have observed that normal, diploid Syrian hamster embryo cells (SHE) express the enzyme telomerase but undergo senescence at the end of their replicative lifespan. After 20-30 population doublings (pd) these cells cease proliferating, enlarge in size, exhibit a pH 6.0 senescence-associated beta-galactosidase activity, and fail to phosphorylate the RB protein or enter into S-phase after serum stimulation. We have observed that SHE cells express telomerase throughout their replicative lifespan and that the average telomere length does not appear to decrease, remaining at about 23 kb in senescent cells. In addition, individual clones of SHE cells also have telomerase activity and telomeres that do not decrease in length, ruling out the possibility that there is a rare, immortal subpopulation of telomerase-expressing cells that is lost during passaging. Together, these data suggest that SHE cells are likely to senesce by a mechanism that does not involve telomere loss.