Klotho RNAi induces premature senescence of human cells via a p53/p21 dependent pathway

被引：81

作者：

de Oliveira, Rita Machado

机构：

[1] MIT, Dept Biol, Cambridge, MA 02139 USA

[2] Univ Porto, ICBAS, Grad Program Basic & Appl Biol, P-4099003 Oporto, Portugal

来源：

FEBS LETTERS | 2006年 / 580卷 / 24期

基金：

美国国家卫生研究院;

关键词：

Klotho; senescence; aging; p53; human lung fibroblasts; insulin/IGF-1; signaling;

D O I：

10.1016/j.febslet.2006.09.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Klotho has recently emerged as a regulator of aging. To investigate the role of Klotho in the regulation of cellular senescence, we generated stable MRC-5 human primary fibroblast cells knockdown for Klotho expression by RNAL Downregulation of Klotho dramatically induces premature senescence with a concomitant upregulation of p21. The upregulation of p21 is associated with cell cycle arrest at G1/S boundary. Knockdown of p53 in the Klotho attenuated MRC-5 cells restores normal growth and replicative potential. These results demonstrate that Klotho normally regulates cellular senescence by repressing the p53/p21 pathway. Our findings implicate Klotho as a regulator of aging in primary human fibroblasts. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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收藏

页码：5753 / 5758

页数：6

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