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DNA damage in aging, the stem cell perspective
Open accessAbstract
DNA damage is one of the most consistent cellular process proposed to contribute to aging. The maintenance of genomic and epigenomic integrity is critical for proper function of cells and tissues throughout life, and this homeostasis is under constant strain from both extrinsic and intrinsic insults. Considering the relationship between lifespan and genotoxic burden, it is plausible that the longest-lived cellular populations would face an accumulation of DNA damage over time. Tissue-specific stem cells are multipotent populations residing in localized niches and are responsible for maintaining all lineages of their resident tissue/system throughout life. However, many of these stem cells are impacted by genotoxic stress. Several factors may dictate the specific stem cell population response to DNA damage, including the niche location, life history, and fate decisions after damage accrual. This leads to differential handling of DNA damage in different stem cell compartments. Given the importance of adult stem cells in preserving normal tissue function during an individual's lifetime, DNA damage sensitivity and accumulation in these compartments could have crucial implications for aging. Despite this, more support for direct functional effects driven by accumulated DNA damage in adult stem cell compartments is needed. This review will present current evidence for the accumulation and potential influence of DNA damage in adult tissue-specific stem cells and propose inquiry directions that could benefit individual healthspan.
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“DNA damage and markers of DDR activation have been observed in various stem cell types in different tissues and species, during normal and pathological ageing121,122, suggesting that stem cells are not immune to DNA damage accumulation and DDR activation123.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [122]
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Metadata
- Authors
- McNeely, T., Leone, M., Yanai, H., & Beerman, I.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Beerman, Isabel
- Venue
- Human Genetics
- Published
- 2019-07-19
- Volume
- 139
- Issue
- 3
- Pages
- 309-331
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- PMC
- PMC6980431
- OpenAlex
- W2962795074
- Semantic Scholar
- e941bddd222e771b8a09dabfd854113fc588a2ed
- Cited by
- 52
- References
- 274
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 14 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 10
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIA / NIH Intramural Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Keywords
- DNA damage, aging, adult stem cells, genotoxic stress, stem cell niche, genome stability, lifespan, healthspan, stem cell fate
- MeSH terms
- Aging, Animals, DNA Damage, Homeostasis, Humans, Stem Cells
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