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Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks - Nature Cell Biology

  • ️Barrett, J. Carl
  • ️Mon Feb 02 2004
  • Brief Communication
  • Published: 02 February 2004

Nature Cell Biology volume 6, pages 168–170 (2004)Cite this article

Abstract

Humans and animals undergo ageing, and although their primary cells undergo cellular senescence in culture, the relationship between these two processes is unclear1,2. Here we show that γ-H2AX foci (γ-foci), which reveal DNA double-strand breaks (DSBs)3,4, accumulate in senescing human cell cultures and in ageing mice. They colocalize with DSB repair factors, but not significantly with telomeres. These cryptogenic γ-foci remain after repair of radiation-induced γ-foci, suggesting that they may represent DNA lesions with unrepairable DSBs. Thus, we conclude that accumulation of unrepairable DSBs may have a causal role in mammalian ageing.

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Figure 1: Accumulation of γ-foci during senescence in culture and in ageing mice.

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Acknowledgements

We thank C. Redon, D. Pilch and T. Furuta for their thoughtful advice, and I. Kareva for her technical assistance.

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Authors and Affiliations

  1. Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892, MD, USA

    Olga A. Sedelnikova & William M. Bonner

  2. Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892, MD, USA

    Izumi Horikawa & J. Carl Barrett

  3. Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892, MD, USA

    Drazen B. Zimonjic & Nicholas C. Popescu

Authors

  1. Olga A. Sedelnikova

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  2. Izumi Horikawa

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  3. Drazen B. Zimonjic

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  4. Nicholas C. Popescu

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  5. William M. Bonner

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  6. J. Carl Barrett

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Corresponding author

Correspondence to William M. Bonner.

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The authors declare no competing financial interests.

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Sedelnikova, O., Horikawa, I., Zimonjic, D. et al. Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nat Cell Biol 6, 168–170 (2004). https://doi.org/10.1038/ncb1095

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  • Received: 03 November 2003

  • Accepted: 07 January 2004

  • Published: 02 February 2004

  • Issue Date: 01 February 2004

  • DOI: https://doi.org/10.1038/ncb1095

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