Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1
Open accessAbstract
Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose) polymerase-1 (PARP-1) and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κ b and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline) in human fibroblasts (HF) cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP). Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.
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Fisetin is protective when administered in the presence of OS, but if given chronically in physiological conditions, it may cause telomere shortening and promote senescence.
“If on the one hand fisetin is protective when administered in the presence of OS, if it is given chronically in physiological conditions, it may even cause telomere shortening, therefore promoting senescence [275].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [275]
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The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
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- Authors
- Boesten, D. M. P. H. J., de Vos-Houben, J. M. J., Timmermans, L., den Hartog, G. J. M., Bast, A., & Hageman, G. J.
- Affiliations
- Maastricht University (NL)
- Department of Toxicology, Maastricht University, P.O. Box 6200 MD, Maastricht, The Netherlands
- Corresponding author
- Boesten, Daniëlle M. P. H. J.
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2013
- Volume
- 2013
- Pages
- 1-10
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC3844163
- OpenAlex
- W2154476866
- Cited by
- 37
- References
- 69
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 4
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- PARP1, accelerated aging, chronic oxidative stress, telomere shortening, telomere stability, PARP1 inhibition, fisetin, minocycline, tert-butyl hydroperoxide, human fibroblasts, cellular senescence, chronic inflammatory diseases, NF-κB, AP-1
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Chromosomes, Human, Pair 2, Fibroblasts, Flavonoids, HeLa Cells, Humans, Hydrogen Peroxide, Minocycline, Poly Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Telomere, Cellular Senescence, Oxidative Stress, Telomerase, DNA Methylation, tert-Butylhydroperoxide, Flavonols, Telomere Homeostasis
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