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

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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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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