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.