Stress, DNA damage and ageing -- an integrative approach.
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.
von Zglinicki
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Department of Gerontology, Institute for the Health of the Elderly, Wolfson Research Centre, University of Newcastle upon Tyne, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK. t.vonglinicki@ncl.ac.uk
Bürkle
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Kirkwood
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D000375:Aging / Q000235:genetics*; D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D016922:Cellular Senescence; D004249:DNA Damage; D006801:Humans; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases; D013312:Stress, Physiological / Q000235:genetics*; D016615:Telomere
D011065:Poly(ADP-ribose) Polymerases