Replicative senescence in sheep fibroblasts is a p53 dependent process

被引:27
作者
Davis, T
Skinner, JW
Faragher, RGA
Jones, CJ
Kipling, D
机构
[1] Univ Cardiff, Sch Med, Dept Pathol, Cardiff CF14 4XN, S Glam, Wales
[2] Univ Brighton, Sch Pharm & Biomol Sci, Brighton BN2 4GJ, E Sussex, England
基金
英国生物技术与生命科学研究理事会;
关键词
ageing; animal models; cellular immortalisation; p21(WAFI); proliferative lifespan barriers; telomerase;
D O I
10.1016/j.exger.2004.09.004
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
Studies on telomere and telomerase biology are fundamental to the understanding of human ageing, and age-related diseases such as cancer. However, human studies are hampered by the lack of fully reflective animal model systems. Here we describe,basic studies of telomere length and telomerase activity in sheep tissues and cells. Terminal restriction fragment lengths from sheep tissues ranged from 9 to 23 kb, with telomerase activity present in testis but suppressed in somatic tissues. Sheep fibroblasts had a finite lifespan in culture, after which the cells entered senescence. During in vitro growth the mean terminal restriction fragment lengths decreased in size at a rate of 210 and 350 bp per population doubling (PD). Senescent skin fibroblasts had increased levels of p53 and p21(WAF1) Compared to young cells. Incubation of senescent cells with siRNA duplexes specific for p53 suppressed p53 expression and allowed the cells to re-enter the cell cycle. Five PDs beyond senescence the siRNA-treated cells reached a second proliferative barrier. This study shows that telomere biology in sheep is similar to that in humans, with senescence in sheep GM03550 fibroblasts being a telomere-driven, p53-(p21(WAF1))-dependent process. Therefore sheep may represent an alternative model system for studying telomere biology, replicative senescence, and by implication human ageing. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:17 / 26
页数:10
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