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

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

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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Crossref · 10.1074/jbc.m207939200

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  • Overexpressing SOD3 or reducing intracellular peroxide reduces the rate of telomere shortening and extends replicative lifespan of human fibroblasts.

    “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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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
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
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
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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