Stress, DNA damage and ageing -: an integrative approach

被引：143

作者：

von Zglinicki, T ^{[1
]}

Bürkle, A ^{[1
]}

Kirkwood, TBL ^{[1
]}

机构：

[1] Newcastle Univ, Newcastle Gen Hosp, Wolfson Res Ctr, Inst Hlth Elderly,Dept Gerontol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England

来源：

EXPERIMENTAL GERONTOLOGY | 2001年 / 36卷 / 07期

关键词：

cell replicative senescence; stress; oxidative damage; DNA repair; telomere loss; poly(ADP-ribose)polymerase (PARP); mitochondrial mutations; mathematical models;

D O I：

10.1016/S0531-5565(01)00111-5

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：

Ageing is highly complex, involving multiple mechanisms at different levels. Nevertheless, recent evidence suggests that several of the most important mechanisms are linked via endogenous stress-induced DNA damage caused by reactive oxygen species (ROS). Understanding how such damage contributes to age-related changes requires that we explain how these different mechanisms relate to each other and potentially interact. In this article, we review the contributions of stress-induced damage to cellular DNA through (i) the role of damage to nuclear DNA and its repair mediated via the actions of poly(ADP-ribose) polymerase-1, (ii) the role of damage to telomeric DNA and its contribution to telomere-driven cell senescence, and (iii) the role of damage to and the accumulation of mutations in mitochondrial DNA. We describe how an integrative approach to studying these mechanisms, coupled with computational modelling, may be of considerable importance in resolving some of the complexity of cellular ageing. (C) 2001 Elsevier Science Inc. All rights reserved.

引用

页码：1049 / 1062

页数：14

共 89 条

[31] Postnatal growth failure, short life span, and early onset of cellular senescence and subsequent immortalization in mice lacking the xeroderma pigmentosum group G gene [J].