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Cellular and epigenetic drivers of stem cell ageing
Abstract
Adult tissue stem cells have a pivotal role in tissue maintenance and regeneration throughout the lifespan of multicellular organisms. Loss of tissue homeostasis during post-reproductive lifespan is caused, at least in part, by a decline in stem cell function and is associated with an increased incidence of diseases. Hallmarks of ageing include the accumulation of molecular damage, failure of quality control systems, metabolic changes and alterations in epigenome stability. In this Review, we discuss recent evidence in support of a novel concept whereby cell-intrinsic damage that accumulates during ageing and cell-extrinsic changes in ageing stem cell niches and the blood result in modifications of the stem cell epigenome. These cumulative epigenetic alterations in stem cells might be the cause of the deregulation of developmental pathways seen during ageing. In turn, they could confer a selective advantage to mutant and epigenetically drifted stem cells with altered self-renewal and functions, which contribute to the development of ageing-associated organ dysfunction and disease.
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“The exact mechanism for decreased stem and progenitor cell capacity to rejuvenate is not known, but the common mechanisms of stem cell aging can be explained by some cell-intrinsic and extrinsic factors including telomere attrition, molecular damage, epigenetic drift and deregulation of developmental pathways”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Ermolaeva et al. 2018
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Metadata
- Authors
- Ermolaeva, M., Neri, F., Ori, A., & Rudolph, K. L.
- Affiliations
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Corresponding author
- Ermolaeva, Maria
- Neri, Francesco
- Rudolph, K. Lenhard
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2018-06-01
- Volume
- 19
- Issue
- 9
- Pages
- 594-610
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2805636495
- Semantic Scholar
- 422884d09599558429d720d9e413dadf9c506510
- Cited by
- 272
- References
- 258
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 37 · 2023: 42 · 2022: 33 · 2021: 49 · 2020: 33 · 2019: 27 · 2018: 5
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- stem cell aging, epigenetic drift, stem cell niche, tissue homeostasis, age-related diseases, stem cell self-renewal, organ dysfunction
- MeSH terms
- Animals, Homeostasis, Humans, Stem Cells, Cellular Senescence, Epigenesis, Genetic, Epigenomics
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