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Mild Hyperoxia Shortens Telomeres and Inhibits Proliferation of Fibroblasts: A Model for Senescence?
Abstract
Mild oxidative stress as exerted by culture of human WI-38 fibroblasts under 40% oxygen partial pressure blocks proliferation irreversibly after one to three population doublings. Hyperoxically blocked cells are similar to senescent ones in terms of general morphology and lipofuscin accumulation. Moreover, they, like senescent fibroblasts, are blocked preferentially in G1 as evident from DNA content measurements by flow cytometry. Southern blotting of AluI- and HinfI-restricted genomic DNA shows an increase of the rate of telomere shortening from 90 bp per population doubling under normoxia to more than 500 bp per population doubling under hyperoxia. In every case, proliferation is blocked if a telomere cutoff length of about 4 kb is arrived at. The fact that telomere length correlates with the final inhibition of proliferation under conditions of varied oxidative stress, while the population doubling level does not, suggests that telomere shortening provides the signal for cell cycle exit in senescence. In postmitotic cells, no further telomere shortening occurs. However, the sensitivity of terminal restriction fragments to S1 nuclease increases, indicating the accumulation of single-strand breaks in telomeres of nondividing fibroblasts. This effect is found both under normoxic and hyperoxic culture, although it is more pronounced under conditions of higher oxidative stress. It might be speculated that accumulation of single-strand breaks and the resultant loss of distal single-stranded fragments during replication could be a major cause of telomere shortening, possibly more important than incomplete replication per se.
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“telomere shortening is accelerated when cells are exposed to mild oxidative stress, leading to reduced replicative capacity and a phenotype that resembles replicative senescence (von Zglinicki et al., 1995, von Zglinicki, 2002, Saretzki et al., 2003).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as von Zglinicki et al., 1995
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Metadata
- Authors
- von Zglinicki, T., Saretzki, G., Döcke, W., & Lotze, C.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- ORCID
- Saretzki, Gabriele
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 1995-09
- Volume
- 220
- Issue
- 1
- Pages
- 186-193
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W2071673220
- Cited by
- 856
- References
- 0
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 12 · 2023: 15 · 2022: 23 · 2021: 27 · 2020: 18 · 2019: 27 · 2018: 16 · 2017: 19 · 2016: 23 · 2015: 27 · 2014: 26 · 2013: 28 · 2012: 34
- FWCI
- 8.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- hyperoxia, telomere shortening, cellular senescence, fibroblast proliferation, oxidative stress, WI-38 cells, G1 cell cycle arrest, telomere length, terminal restriction fragments, S1 nuclease, lipofuscin, postmitotic cells
- MeSH terms
- Aerobiosis, Cell Cycle, Cells, Cultured, Fibroblasts, Flow Cytometry, Lipofuscin, Microscopy, Electron, Oxygen, Phenotype, Ploidies, Oligonucleotide Probes, Telomere, Cellular Senescence, Oxidative Stress
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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