title: Senescence and immortalization of human cells.
abstract: Following a limited number of population doublings (PD), human diploid somatic cells enter the terminal proliferation arrest state of senescence. This is an intrinsic mechanism which involves p53- and pRB/p16INK4-mediated pathways. The most popular candidate for the counting mechanism which measures the age of a cell in PD is telomere shortening. Recent studies have shown that senescence can also be induced independently of a PD level by various factors; this premature senescence also appears to involve the activity of p53 and/or p16INK4. Immortalization of cells requires abrogation of p53 and pRB-mediated terminal proliferation arrest and/or activation of a telomere maintenance mechanism. The central role of telomeres in human cell senescence and immortalization has received much attention; however there is evidence that senescence can occur independently of telomere length and that genes that are not necessarily involved in telomere maintenance are involved in immortalization.
authors.affiliation: National Institute of Bioscience and Human-Technology, AIST, 1-1 Higashi, Tsukuba Science City, Ibaraki 305-8566, Japan.
authors.forename: E L
authors.initials: EL
authors.lastname: Duncan
authors.forename: R
authors.initials: R
authors.lastname: Wadhwa
authors.forename: S C
authors.initials: SC
authors.lastname: Kaul
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D006801:Humans; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016615:Telomere / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53