Senescence and immortalization of human cells

TY - JOUR

T1 - Senescence and immortalization of human cells

AU - Duncan, Emma L.

AU - Wadhwa, Renu

AU - Kaul, Sunil C.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Human

KW - Immortalization

KW - Senescence

UR - http://www.scopus.com/inward/record.url?scp=0034575087&partnerID=8YFLogxK

U2 - 10.1023/A:1010000132671

DO - 10.1023/A:1010000132671

M3 - Review article

C2 - 11707927

AN - SCOPUS:0034575087

SN - 1389-5729

VL - 1

SP - 103

EP - 121

JO - BIOGERONTOLOGY

JF - BIOGERONTOLOGY

IS - 2

ER -