Molecular mechanisms of cellular senescence

Cellular senescence is a stress response characterized by a stable cell cycle arrest and with numerous macromolecular alterations including a hypersecretory phenotype. Besides acting as a potent tumor suppressor mechanism via the cell autonomous cell cycle arrest, senescence participates in various biological events via the noncell autonomous secretory phenotype. Acute and transient senescent cells are thought to be part of a programmed process that contributes to tissue remodeling and regeneration. In contrast, chronic accumulation of senescent cells is associated to disrupted tissue homeostasis and inflammation, and considered a leading cause for the onset and progression of different age-related diseases, including cancer. These different and oftentimes opposite functional roles are partly explained by recent evidences supporting the concept that the senescence state is an exquisitely dynamic process. In this chapter, we discuss the mechanisms regulating induction and establishment of various senescence programs, with particular emphasis on their biological heterogeneity and functional implications.