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Nat Cell Biol. 2014 Mar;16(3):201-7. doi: 10.1038/ncb2928.

Impact of genomic damage and ageing on stem cell function.

Author information

1
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.
2
Department of Pediatric and Adolescent Medicine and the Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
3
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.
4
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, Z├╝lpicher Str. 47a, 50674 Cologne, Germany.

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.

PMID:
24576896
PMCID:
PMC4214082
DOI:
10.1038/ncb2928
[Indexed for MEDLINE]
Free PMC Article

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