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PMID: 17986462 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

DNA damage in telomeres and mitochondria during cellular senescence: is there a connection?

Nucleic acids research ·Vol. 35 ·No. 22 ·2007-00-00 ·Pages 7505-13

Passos JF, Saretzki G, von Zglinicki T

Abstract

Cellular senescence is the ultimate and irreversible loss of replicative capacity occurring in primary somatic cell culture. It is triggered as a stereotypic response to unrepaired nuclear DNA damage or to uncapped telomeres. In addition to a direct role of nuclear DNA double-strand breaks as inducer of a DNA damage response, two more subtle types of DNA damage induced by physiological levels of reactive oxygen species (ROS) can have a significant impact on cellular senescence: Firstly, it has been established that telomere shortening, which is the major contributor to telomere uncapping, is stress dependent and largely caused by a telomere-specific DNA single-strand break repair inefficiency. Secondly, mitochondrial DNA (mtDNA) damage is closely interrelated with mitochondrial ROS production, and this might also play a causal role for cellular senescence. Improvement of mitochondrial function results in less telomeric damage and slower telomere shortening, while telomere-dependent growth arrest is associated with increased mitochondrial dysfunction. Moreover, telomerase, the enzyme complex that is known to re-elongate shortened telomeres, also appears to have functions independent of telomeres that protect against oxidative stress. Together, these data suggest a self-amplifying cycle between mitochondrial and telomeric DNA damage during cellular senescence.

MeSH Terms
Cellular Senescence/genetics DNA Damage DNA, Mitochondrial/chemistry Humans Mitochondria/metabolism Mutation Oxidative Stress Reactive Oxygen Species/metabolism Telomerase/metabolism Telomere/metabolism
Chemicals
DNA, Mitochondrial Reactive Oxygen Species Telomerase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Passos João F
Henry Wellcome Laboratory for Biogerontology Research, Institute for Ageing and Health, University of Newcastle, Newcastle upon Tyne NE4 6BE, UK.
Saretzki Gabriele
von Zglinicki Thomas
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkm893
Published
2007-00-00
Epub
2007-00-05
Pages
7505-13
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2190715
Subset
IM
Grants
Medical Research Council · G0601333 · United Kingdom
External Links
PubMed source DOI: 10.1093/nar/gkm893 PMC Full Text View journal details
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