The love and hate relationship between cellular senescence and stemness

Cellular senescence and stemness represent two biological entities with several opposing properties. However, both senescence and stemness serve to maintain tissue homeostasis, via different mechanisms. In adults, while non-dividing senescent cells represent a major barrier to potentially harmful cell insults, propagating stem cells are responsible for restoring the structure and functionality of damaged tissue. In this review, we highlight distinct cellular settings where an antagonistic relationship between the two states is naturally established. In contrast, major synergy between senescence and stemness is observed primarily in cancer, where inherent senescent cell features may actively promote the emergence of cancer stem cells. As the complex interplay between senescence and stemness may heavily vary between different cell types and physiological contexts, elucidating the nature of the interaction and the potential effects per case, is of considerable clinical importance.