Stress-induced senescence

Stress-induced senescence is a very broad concept encompassing a variety of stresses and sources of damage to cells. These stresses act via intracellular pathways, which may be multiple, to a final common state of irreversible cell division. In this state the cell is held in the nondividing state by the combination of CDKI activity, heterochromatin formation, and gene expression changes. Here, a case is made that, although the mediators of stress-induced senescence may be multiple, the p38 MAP kinase pathway stands out as potentially the most important. However, both the means by which it may become activated by stresses and the means by which it acts to cause senescence are both as yet unclear. Future studies should focus on appropriate in vivo models in which stress-induced senescence can be studied under pathophysiologically relevant conditions.