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Impact of genomic damage and ageing on stem cell function

Nature Cell Biology volume 16, pages 201–207 (2014)Cite this article

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Abstract

Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells.

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Figure 1: Cell-autonomous and systemic responses to DNA damage.
Figure 2: Impact of DNA damage on the stem cell environment.
Figure 3: Consequences of DNA damage on clonal selection in tissue stem cells during ageing.

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Acknowledgements

We thank the Else Kröner-Fresenius-Foundation for funding the 5th Else Kröner-Fresenius-Symposium in Molecular Medicine on the 'Role of Stem Cells in Aging, Diseases, and Cancer'. This meeting fostered the discussion on DNA damage in stem cells and was the basis of this Review. We apologize to our colleagues for omitting numerous references due to space limitations.

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Authors and Affiliations

  1. Axel Behrens is at the Mammalian Genetics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK, and the School of Medicine, King's College London, Guy's Campus, London, SE1 1UL, UK,

    Axel Behrens

  2. Jan M. van Deursen is in the Department of Pediatric and Adolescent Medicine and the Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA,

    Jan M. van Deursen

  3. K. Lenhard Rudolph is at the Leibniz Institute of Age Research, Fritz Lipmann Institute e.V., Jena, 07745, Germany, and the Research Group on Molecular Aging, Faculty of Medicine, Friedrich-Schiller-University, Jena, Germany,

    K. Lenhard Rudolph

  4. Björn Schumacher is at the Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, 50931 Cologne, and the Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), Institute for Genetics, and Systems Biology of Cologne, University of Cologne, Zülpicher Str. 47a, 50674 Cologne, Germany,

    Björn Schumacher

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  1. Axel Behrens
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Correspondence to Axel Behrens, Jan M. van Deursen, K. Lenhard Rudolph or Björn Schumacher.

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Behrens, A., van Deursen, J., Rudolph, K. et al. Impact of genomic damage and ageing on stem cell function. Nat Cell Biol 16, 201–207 (2014). https://doi.org/10.1038/ncb2928

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