Senescence and immortalization of human cells

被引:39
作者
Duncan, EL
Wadhwa, R
Kaul, SC
机构
[1] AIST, Natl Inst Biosci & Human Technol, Tsukuba, Ibaraki 3058566, Japan
[2] Chugai Res Inst Mol Med, Niihari, Ibaraki 30041, Japan
关键词
human; immortalization; senescence;
D O I
10.1023/A:1010000132671
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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/p16(INK4)-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 p16(INK4). 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.
引用
收藏
页码:103 / 121
页数:19
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