Cited by 45Microtubule and mitosis dynamicsGenetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and Senescence

Stem cell ageing and non-random chromosome segregation

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Charville, Gregory W., Rando, Thomas A.·2011·Philosophical Transactions of the Royal Society B: Biological Sciences

Abstract

Adult stem cells maintain the mature tissues of metazoans. They do so by reproducing in such a way that their progeny either differentiate, and thus contribute functionally to a tissue, or remain uncommitted and replenish the stem cell pool. Because ageing manifests as a general decline in tissue function, diminished stem cell-mediated tissue maintenance may contribute to age-related pathologies. Accordingly, the mechanisms by which stem cell regenerative potential is sustained, and the extent to which these mechanisms fail with age, are fundamental determinants of tissue ageing. Here, we explore the mechanisms of asymmetric division that account for the sustained fitness of adult stem cells and the tissues that comprise them. In particular, we summarize the theory and experimental evidence underlying non-random chromosome segregation—a mitotic asymmetry arising from the unequal partitioning of chromosomes according to the age of their template DNA strands. Additionally, we consider the possible consequences of non-random chromosome segregation, especially as they relate to both replicative and chronological ageing in stem cells. While biased segregation of chromosomes may sustain stem cell replicative potential by compartmentalizing the errors derived from DNA synthesis, it might also contribute to the accrual of replication-independent DNA damage in stem cells and thus hasten chronological ageing.

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Crossref · 10.1098/rstb.2010.0279

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  • Stem cells in different tissue compartments exhibit template strand segregation during cell divisions.

    “Emerging evidence has demonstrated that stem cells in different tissue compartments exhibit template strand segregation during cell divisions128.”

    From Molecular regulation of stem cell quiescence (2013) · cites this paper as [128]

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Authors
Charville, G. W., & Rando, T. A.
Affiliations
  • Stanford Medicine (US)
  • VA Palo Alto Health Care System (US)
Corresponding author
Rando, Thomas A.
Venue
Philosophical Transactions of the Royal Society B: Biological Sciences
Published
2011-01-12
Volume
366
Issue
1561
Pages
85-93
ISSN
  • 0962-8436 (ISSN-L)
  • 1471-2970
OpenAlex
W2133799215
Cited by
45
References
67
Citations by year
2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 1 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 9 · 2012: 9
FWCI
0.69
Type
journal article
Language
en
Open access
Locations
  • Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Federation for Aging Research
  • Glenn Foundation for Medical Research
  • Fondation pour la Recherche Médicale
  • National Institutes of Health (DP1OD000392, R01 AG23806)
  • National Institute on Aging (R01 AG23806, F30 AG35521, R37AG023806, R01AG023806, F30AG035521)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
adult stem cells, stem cell aging, asymmetric cell division, chronological aging, DNA damage, tissue aging, stem cell self-renewal
MeSH terms
Animals, Cell Differentiation, Humans, Mitosis, Cellular Senescence, Cell Lineage, Chromosome Segregation, Adult Stem Cells

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