High Doses of Synthetic Antioxidants Induce Premature Senescence in Cultivated Mesenchymal Stem Cells
Open accessAbstract
Stress-induced premature senescence program is known to be activated in cells by various genotoxic stressors, and oxidative stress is considered to be the main of those. To this end, many studies discover antioxidants as protective anti-aging agents. In the current study, we examined the effects of different antioxidants (Tempol, resveratrol, NAC, DPI) on the mesenchymal stem cells maintained in normal physiological conditions. We used high, but non-cytotoxic antioxidant doses which are widely used in laboratory practice to protect cells from oxidative damage. We show that these substances induce reversible block of cell proliferation and do not cause any genotoxic effects when applied to the quiescent cells. However, the same doses of the same substances, when applied to the proliferating cells, can induce irreversible cell cycle arrest, DNA strand breaks accumulation and DNA damage response activation. As a consequence, antioxidant-induced DNA damage results in the stress-induced premature senescence program activation. We conclude that high doses of antioxidants, when applied to the proliferating cells that maintain physiological levels of reactive oxygen species, can cause DNA damage and induce premature senescence which suggests to re-estimate believed unconditional anti-aging antioxidant properties.
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High doses of antioxidants promote cellular senescence.
“Accordingly, it has been reported that high doses of antioxidants promote cellular senescence [156,475,476].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [476]
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- Authors
- Kornienko, J. S., Smirnova, I. S., Pugovkina, N. A., Ivanova, J. S., Shilina, M. A., Grinchuk, T. M., Shatrova, A. N., Aksenov, N. D., Zenin, V. V., Nikolsky, N. N., & Lyublinskaya, O. G.
- Affiliations
- Russian Academy of Sciences (RU)
- Corresponding author
- Lyublinskaya, O. G.
- Venue
- Scientific Reports
- Published
- 2019-02-04
- Volume
- 9
- Issue
- 1
- Pages
- 1296-1296
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6361906
- OpenAlex
- W2914548578
- Cited by
- 135
- References
- 66
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 18 · 2023: 30 · 2022: 24 · 2021: 14 · 2020: 21 · 2019: 5 · 2016: 1
- FWCI
- 10.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Russian Science Foundation (14-50-00068)
- Topics
- Health Sciences › Medicine › Physiology › 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
- stress-induced premature senescence, mesenchymal stem cells, antioxidants, oxidative stress, DNA damage response, DNA strand breaks, cell cycle arrest, cell proliferation, anti-aging, reactive oxygen species, tempol, resveratrol, N-acetylcysteine, DPI, genotoxicity
- MeSH terms
- Antioxidants, DNA Damage, Female, Humans, Cellular Senescence, Reactive Oxygen Species, Oxidative Stress, Cell Proliferation, Cell Cycle Checkpoints, Mesenchymal Stem Cells
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