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Extracellular Superoxide Dismutase Is a Major Antioxidant in Human Fibroblasts and Slows Telomere Shortening
Open accessAbstract
There is good evidence that telomere shortening acts as a biological clock in human fibroblasts, limiting the number of population doublings a culture can achieve. Oxidative stress also limits the growth potential of human cells, and recent data show that the effect of mild oxidative stress is mediated by a stress-related increased rate of telomere shortening. Thus, fibroblast strains have donor-specific antioxidant defense, telomere shortening rate, and growth potential. We used low-density gene expression array analysis of fibroblast strains with different antioxidant potentials and telomere shortening rates to identify gene products responsible for these differences. Extracellular superoxide dismutase was identified as the strongest candidate, a correlation that was confirmed by Northern blotting. Over-expression of this gene in human fibroblasts with low antioxidant capacity increased total cellular superoxide dismutase activity, decreased the intracellular peroxide content, slowed the telomere shortening rate, and elongated the life span of these cells under normoxia and hyperoxia. These results identify extracellular superoxide dismutase as an important antioxidant gene product in human fibroblasts, confirm the causal role of oxidative stress for telomere shortening, and strongly suggest that the senescence-like arrest under mild oxidative stress is telomere-driven.
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“overexpressing the antioxidant enzyme superoxide dismutase (SOD3) in human fibroblasts, or reducing the levels of intracellular peroxide using antioxidants, are effective in reducing the rate of telomere shortening and extending replicative lifespan of these cells (von Zglinicki et al., 2000, Serra et al., 2003).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Serra et al., 2003
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Metadata
- Authors
- Serra, V., von Zglinicki, T., Lorenz, M., & Saretzki, G.
- Affiliations
- Stiftung Charité (DE)
- Newcastle University (GB)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 278
- Issue
- 9
- Pages
- 6824-6830
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2128014750
- Cited by
- 278
- References
- 41
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 18 · 2020: 6 · 2019: 11 · 2018: 8 · 2017: 7 · 2016: 7 · 2015: 14 · 2014: 13 · 2013: 13 · 2012: 14
- FWCI
- 10.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- 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
- extracellular superoxide dismutase, telomere shortening, human fibroblasts, oxidative stress, antioxidant defense, cellular aging, replicative lifespan, hyperoxia, hydrogen peroxide, gene expression profiling, senescence
- MeSH terms
- Actins, Aging, Hypoxia, Antioxidants, Cells, Cultured, Cytoplasm, Fibroblasts, Humans, Superoxide Dismutase, Blotting, Northern, Gene Expression, Telomere, Oxidative Stress, Reverse Transcriptase Polymerase Chain Reaction
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