The role of chromatin reorganization in the process of cellular senescence.

Cellular senescence is a state of irreversible growth arrest and thought to be a tumor suppressive mechanism. In addition, it has been reported that cellular senescence may play an important role in wound healing, tissue remodeling, organismal aging and age-related diseases. This loss of ability to divide, associated with senescence, is induced by factors that are intrinsic, such as genetically defined pathways and telomere erosion, and extrinsic eg. DNA damage, oxidative stress, over-expression of oncogenes and inadequate growth conditions. The p53/p21 and RB/p16 pathways are key to the cell cycle arrest associated with cellular senescence. Extensive molecular changes occur when cells become senescent, as gene expression profiling of senescent versus young cells has demonstrated, and this is, in part, due to alterations in chromatin structure. Here, we review the molecular basis of the cell cycle arrest in cellular senescence, focusing on chromatin regulation. We also summarize our current knowledge of the role of cellular senescence in vivo.