Cellular senescence involves irreversible growth arrest accompanied by phenotypic changes such as enlarged morphology, reorganization of chromatin through formation of senescence-associated heterochromatic foci (SAHF), and changes in gene expression that result in secretion of a number of proteins that alter local tissue environment, known as senescence-associated secretory phenotype (SASP).
Senescence is considered to be a cancer protective mechanism and is also involved in aging. Senescent cells accumulate in aged tissues (reviewed by Campisi 1997 and Lopez-Otin 2013), which may be due to an increased senescence rate and/or decrease in the rate of clearance of senescent cells. In a mouse model of accelerated aging, clearance of senescent cells delays the onset of age-related phenotypes (Baker et al. 2011).
Cellular senescence can be triggered by the aberrant activation of oncogenes or loss-of-function of tumor suppressor genes, and this type of senescence is known as the oncogene-induced senescence, with RAS signaling-induced senescence being the best studied. Oxidative stress, which may or may not be caused by oncogenic RAS signaling, can also trigger senescence. Finally, the cellular senescence program can be initiated by DNA damage, which may be caused by reactive oxygen species (ROS) during oxidative stress, and by telomere shortening caused by replicative exhaustion which may be due to oncogenic signaling. The senescent phenotype was first reported by Hayflick and Moorhead in 1961, when they proposed replicative senescence as a mechanism responsible for the cessation of mitotic activity and morphological changes that occur in human somatic diploid cell strains as a consequence of serial passaging, preventing the continuous culture of untransformed cells-the Hayflick limit (Hayflick and Moorhead 1961).
Senescent cells may remain viable for years, such as senescent melanocytes of moles and nevi, or they can be removed by phagocytic cells. The standard marker for immunohistochemical detection of senescent cells is senescence-associated beta-galactosidase (SA-beta-Gal), a lysosomal enzyme that is not required for senescence.
For a recent review, please refer to Collado et al. 2007, Adams 2009, Kuilman et al. 2010. For a review of differential gene expression between senescent and immortalized cells, please refer to Fridman and Tainsky 2008.
|17662938||Cellular senescence in cancer and aging||Cell||2007|
|19818705||Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence||Mol. Cell||2009|
|21078816||The essence of senescence||Genes Dev.||2010|
|17667954||Cellular senescence: when bad things happen to good cells||Nat. Rev. Mol. Cell Biol.||2007|
|9282108||The biology of replicative senescence||Eur. J. Cancer||1997|
|23746838||The hallmarks of aging||Cell||2013|
|22048312||Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders||Nature||2011|
|13905658||The serial cultivation of human diploid cell strains||Exp. Cell Res.||1961|
|18711403||Critical pathways in cellular senescence and immortalization revealed by gene expression profiling||Oncogene||2008|