Induction of Premature Cell Senescence Stimulated by High Doses of Antioxidants Is Mediated by Endoplasmic Reticulum Stress
Open accessAbstract
In our previous study, we found that high doses of several substances with antioxidant capacities (Tempol, resveratrol, diphenyleneiodonium) can cause genotoxic stress and induce premature senescence in the human mesenchymal stem cells (MSCs). Here, using whole-transcriptome analysis, we revealed the signs of endoplasmic reticulum stress and unfolded protein response (UPR) in MSCs stressed with Tempol and resveratrol. In addition, we found the upregulation of genes, coding the UPR downstream target APC/C, and E3 ubiquitin ligase that regulate the stability of cell cycle proteins. We performed the molecular analysis, which further confirmed the untimely degradation of APC/C targets (cyclin A, geminin, and Emi1) in MSCs treated with antioxidants. Human fibroblasts responded to antioxidant applications similarly. We conclude that endoplasmic reticulum stress and impaired DNA synthesis regulation can be considered as potential triggers of cell damage and premature senescence stimulated by high-dose antioxidant treatments.
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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 [475]
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- Authors
- Lyublinskaya, O., Kornienko, J., Ivanova, J., Pugovkina, N., Alekseenko, L., Lyublinskaya, E., Tyuryaeva, I., Smirnova, I., Grinchuk, T., Shorokhova, M., Krasnenko, A., Plotnikov, N., & Nikolsky, N.
- Affiliations
- Russian Academy of Sciences (RU)
- Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Tikhoretskii pr. 4, 194064 St. Petersburg, Russia
- Genotek LLC, Nastavnicheskii per. 17/1, 105120 Moscow, Russia
- Corresponding author
- Lyublinskaya, Olga
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2021-10-31
- Volume
- 22
- Issue
- 21
- Pages
- 11851
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC8584632
- OpenAlex
- W3210540760
- Cited by
- 13
- References
- 60
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 1
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (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, cc-by-sa)
- Funders
- Russian Foundation for Basic Research (19-04-00994)
- Russian Science Foundation (21-74-20178)
- 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 › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Keywords
- endoplasmic reticulum stress, unfolded protein response, antioxidants, mesenchymal stem cells, fibroblasts, genotoxic stress, tempol, resveratrol, diphenyleneiodonium, anaphase-promoting complex, E3 ubiquitin ligase, protein degradation, cyclin A, geminin, Emi1, DNA synthesis regulation
- MeSH terms
- Antioxidants, Cell Line, Humans, Cellular Senescence, Mesenchymal Stem Cells, Endoplasmic Reticulum Stress
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