cellular senescence

Definition : Cellular senescence is the process that limits the replicative life span of normal human cells in culture.

The senescent phenotype entails an essentially permanent arrest of cell proliferation that can be reversed under certain.

Senescent cells assume a distinctive enlarged and flattened morphology. Senescent cells accumulate in diverse tissues.

Cells continually experience stress and damage from exogenous and endogenous sources, and their responses range from complete recovery to cell death.

Proliferating cells can initiate an additional response by adopting a state of permanent cell-cycle arrest that is termed cellular senescence.

Understanding the causes and consequences of cellular senescence has provided novel insights into how cells react to stress, especially genotoxic stress, and how this cellular response can affect complex organismal processes such as the development of cancer and ageing.

Detection

They stain positive for the lysosomal senescence-associated beta-galactosidase (SA-beta-galactosidase). This histochemically detectable enzyme activity is strongly associated with senescence.

All senescent cells show changes in gene expression that appear unrelated to growth arrest.

Many, but not all, senescent cells become resistant to apoptosis, which may explain why they accumulate in vivo.

Oncogenes

Oncogene activation in normal cells induces a permanent proliferative arrest known as cellular senescence. This phenomenon restrains the expansion of cells that bear an activated oncogene and acts as a powerful tumor-suppressive process.

Some oncogenes alter the DNA-replication process and cause DNA-damage accumulation. DNA-damage checkpoint-response activation together with the increased appearance of heterochromatin formation that leads to transcriptional silencing of proliferative genes are, presently, the two main mechanisms known that establish and maintain oncogene-induced senescence.

See also

 senescence

• tissular senescence
• systemic senescence : ageing

 replicative senescence

References

 Di Micco R, Fumagalli M, di Fagagna F. Breaking news: high-speed race ends in arrest—how oncogenes induce senescence. Trends Cell Biol. 2007 Nov;17(11):529-36. PMID: 17980599

 Campisi J, d’Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007 Sep;8(9):729-40. PMID: 17667954

 Mooi WJ, Peeper DS. Oncogene-induced cell senescence—halting on the road to cancer. N Engl J Med. 2006 Sep 7;355(10):1037-46. PMID: 16957149

 Fossel M. Cell senescence in human aging and disease. Ann N Y Acad Sci. 2002 Apr;959:14-23. PMID: 11976181

 Campisi J. Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol. 2001 Nov;11(11):S27-31. PMID: 11684439

 Smith JR, Pereira-Smith OM: Replicative senescence: implications for in vivo aging and tumor suppression. Science 273:63, 1996.