Document Detail

Inducing cellular senescence using defined genetic elements.
MedLine Citation:
PMID:  17634581     Owner:  NLM     Status:  MEDLINE    
Cellular senescence is generally defined as an irreversible state of G1 cell cycle arrest in which cells are refractory to growth factor stimulation. Cellular senescence can be induced through several different mechanisms. Primary mammalian cells display a finite life span, suggesting a mechanism that counts cell divisions. Those cells initially proliferate but eventually enter a state of permanent growth arrest, called replicative senescence. Erosion of telomeric DNA has emerged as a key factor in replicative senescence, which is antagonized during cell immortalization. Nevertheless, besides telomere shortening, there are other mechanisms inducing a growth arrest similar to the replicative senescencent phenotype. Oncogenic or mitogenic signals as well as DNA damage can induce such a phenotype of cellular senescence. All forms of cellular senescence share common signaling pathways and morphological features. Thereby, p53 seems to be essential for the senescence response. Many of these senescence inducing mechanisms can be experimentally recapitulated by the introduction of defined genetic elements. Replicative senescence due to telomere shortening can, for example, be induced by a dominant negative version of telomerase, premature senescence by the overexpression of oncogenic ras, or p16.
Hiroshi Nakagawa; Oliver G Opitz
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Methods in molecular biology (Clifton, N.J.)     Volume:  371     ISSN:  1064-3745     ISO Abbreviation:  Methods Mol. Biol.     Publication Date:  2007  
Date Detail:
Created Date:  2007-07-19     Completed Date:  2007-09-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9214969     Medline TA:  Methods Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  167-78     Citation Subset:  IM    
Gastroenterology Division, Department of Medicine and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
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MeSH Terms
Cell Aging / genetics*
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p16 / genetics*
DNA Damage / genetics*
G1 Phase / genetics*
Genes, ras / genetics*
Signal Transduction / genetics
Telomere / genetics
Tumor Suppressor Protein p53 / genetics*
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p16; 0/Tumor Suppressor Protein p53

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