Transient induction of telomerase expression mediates senescence and reduces tumorigenesis in primary fibroblasts

Significance In the classic view, telomerase is silenced in terminally differentiated cells and its reactivation supports immortalization and unlimited growth of most cancers. Here, we determine the involvement of telomerase during replicative senescence in primary fibroblasts from mouse and human. In both cases, we find that cells that are unable to produce telomerase approach cellular senescence earlier and exhibit a significantly higher rate of malignant transformation than the control cells. Furthermore, an evident upregulation of telomerase expression is detected in wild-type control cells at the presenescence stage, which is accountable for the protection. In conclusion, this study suggests that telomerase has a previously underappreciated, protective role in buffering senescence stresses due to short, dysfunctional telomeres, thereby preventing malignant transformation.