Cited by 278Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsRedox biology and oxidative stress

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Extracellular Superoxide Dismutase Is a Major Antioxidant in Human Fibroblasts and Slows Telomere Shortening

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Serra, Violeta, von Zglinicki, Thomas, Lorenz, Mario, Saretzki, Gabriele·2003·Journal of Biological Chemistry

DOI 10.1074/jbc.m207939200

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Abstract

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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Authors: Serra, V., von Zglinicki, T., Lorenz, M., & Saretzki, G.
Affiliations: Stiftung Charité (DE)
Newcastle University (GB)
ORCID: Serra, Violeta
Lorenz, Mario
Saretzki, Gabriele
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2003-02
Volume: 278
Issue: 9
Pages: 6824-6830
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m207939200
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6536 d)
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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Extracellular Superoxide Dismutase Is a Major Antioxidant in Human Fibroblasts and Slows Telomere Shortening

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