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Impact of genomic damage and ageing on stem cell function
Open accessAbstract
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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“Quite often, defects in DNA repair systems of stem cells accelerate the accumulation of genome instability in lineage-primed progenitor cells during aging [46].”
From Ultraviolet Radiation‐Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging (2016) · cites this paper as [46]
In the citing paper
“Although not a bona fide DNA repair gene, defects in ATM lead to accumulation of genomic damage and premature exhaustion of the stem cell pool in various tissues, including the skin [46].”
From Ultraviolet Radiation‐Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging (2016) · cites this paper as [46]
In the citing paper
“These observations suggest that DDR pathways, evolved to safeguard genomic integrity and maximize survival of the organism13,44–46, may show reduced activity in stem cells with age.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [46]
In the citing paper
“Some studies suggest that the ensuing loss of homeostasis in aging tissues might further create a microenvironment that favors the selection of stem cells with higher self-renewal but also neoplastic potentials46.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [46]
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“Another possibility is that depletion of the NSC pool could be a consequence of an increase in the number of stem cells becoming senescent due to telomeric attrition and/or DNA damage that accumulates with aging (Behrens et al., 2014).”
Metadata
- Authors
- Behrens, A., van Deursen, J. M., Rudolph, K. L., & Schumacher, B.
- Affiliations
- King's College London (GB)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- University of Cologne (DE)
- Corresponding author
- Behrens, Axel
- Rudolph, K. Lenhard
- Schumacher, Björn
- Venue
- Nature Cell Biology
- Published
- 2014-02-28
- Volume
- 16
- Issue
- 3
- Pages
- 201-207
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC4214082
- OpenAlex
- W2054525725
- Cited by
- 207
- References
- 98
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 11 · 2023: 12 · 2022: 10 · 2021: 17 · 2020: 19 · 2019: 27 · 2018: 13 · 2017: 18 · 2016: 20 · 2015: 32 · 2014: 13
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Cancer Research UK (15679)
- National Cancer Institute (R01CA126828)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- genomic instability, aging, stem cell function, DNA damage, stem cell niche, tissue maintenance, tissue repair, carcinogenesis
- MeSH terms
- Aneuploidy, Animals, Cells, Cultured, DNA Damage, DNA Repair, Humans, Neoplasms, Genome, Human, Cellular Senescence, Adult Stem Cells
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