Expansion and Cell-Cycle Arrest: Common Denominators of Cellular Senescence

Cellular senescence is amajor driver of age-related diseases, and senotherapies are being tested in clinical trials. Despite its popularity, cellular senescence is weakly defined and is frequently referred to as irreversible cell-cycle arrest. In this article we hypothesize that cellular senescence is a phenotype that results from the coordination of two processes: cell expansion and cell-cycle arrest. We provide evidence for the compatibility of the proposed model with recent findings showing senescence in postmitotic tissues, wound healing, obesity, and development. We believe our model also explains why some characteristics of senescence can be found in non-senescent cells. Finally, we propose new avenues for research from our model.