Models of initiation of replicative senescence by loss of telomeric DNA

被引:25
作者
Allsopp, RC [1 ]
机构
[1] MCMASTER UNIV,DEPT BIOCHEM,HAMILTON,ON,CANADA
关键词
replicative senescence; telomere; DNA damage;
D O I
10.1016/0531-5565(95)02008-X
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
Situated at the ends of all eukaryotic chromosomes are telomeres, genetic elements that are essential for genomic stability. It has recently been established that telomere length shortens during replicative aging of normal human somatic cells. Although the cause of replicative senescence of somatic cells is still debated, we believe that telomere shortening plays a causal role in this process. In support of this hypothesis, mutant strains of yeast and ciliates that are incapable of maintaining telomere length during cell division eventually acquire a senescent-like phenotype wherein the cells become sickly, stop growing and die. Also, replicative capacity of cultured human skin fibroblast strains shows a strong positive correlation with telomere length. Several theories explaining how telomere shortening could lead to the induction of replicative senescence are now presented, We favor a model in which replicative senescence is caused by the shortening of telomeres below a length that is critical for the maintenance of proper telomere structure and function.
引用
收藏
页码:235 / 243
页数:9
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