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Cited by 21Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsMitochondrial Function and Pathology

Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice

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Guachalla, Luis Miguel, Ju, Zhenyu, Koziel, Rafal, von Figura, Guido, Song, Zhangfa, Fusser, Markus, Epe, Bernd, Jansen-Dűrr, Pidder +1 more·2009·Aging
DOI 10.18632/aging.100030PMC PMC2830048
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Abstract

Telomere shortening represents a causal factor of cellular senescence. At the same time, several lines of evidence indicate a pivotal role of oxidative DNA damage for the aging process in vivo. A causal connection between the two observations was suggested by experiments showing accelerated telomere shorting under conditions of oxidative stress in cultured cells, but has never been studied in vivo. We therefore have analysed whether an increase in mitochondrial derived oxidative stress in response to heterozygous deletion of superoxide dismutase (Sod2(+/-)) would exacerbate aging phenotypes in telomere dysfunctional (mTerc(-/-)) mice. Heterozygous deletion of Sod2 resulted in reduced SOD2 protein levels and increased oxidative stress in aging telomere dysfunctional mice, but this did not lead to an increase in basal levels of oxidative nuclear DNA damage, an accumulation of nuclear DNA breaks, or an increased rate of telomere shortening in the mice. Moreover, heterozygous deletion of Sod2 did not accelerate the depletion of stem cells and the impairment in organ maintenance in aging mTerc(-/-) mice. In agreement with these observations, Sod2 haploinsufficiency did not lead to a further reduction in lifespan of mTerc(-/-) mice. Together, these results indicate that a decrease in SOD2-dependent antioxidant defence does not exacerbate aging in the context of telomere dysfunction.

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  • Other mutations in ROS metabolism, such as SOD2 haploinsufficiency, do not cooperate with telomere dysfunction, and N-acetylcysteine treatment does not rescue progeric phenotypes of late-generation TERT-deficient mice.

    “However, other mutations in genes involved in ROS metabolism, such as SOD2 haploinsufficiency, do not cooperate with telomere dysfunction (Guachalla et al., 2009), and the treatment with N‐acetylcysteine does not rescue progeric phenotypes of late‐generation TERT‐deficient mice (Sahin et al., 2011).”

    From P66SHC deletion improves fertility and progeric phenotype of late-generation TERC-deficient mice but not their short lifespan (2016) · cites this paper as Guachalla et al., 2009

    The Discussion reports that Sod2 haploinsufficiency did not cooperate with telomere dysfunction to accelerate nuclear DNA damage, and the paper reports no exacerbation of aging phenotypes. But the Results say the combination impaired stress-induced ROS detoxification, so the unqualified claim that they do not cooperate is broader than the findings. The N-acetylcysteine clause is attributed to a different citation and is not assessed here. (LLM, conf=0.85)

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Authors
Guachalla, L. M., Ju, Z., Koziel, R., von Figura, G., Song, Z., Fusser, M., Epe, B., Jansen-Dűrr, P., & Rudolph, K. L.
Affiliations
  • Universität Ulm (DE)
  • Institute for Biomedical Aging Research, Austrian Academy of Sciences, A-6020 Innsbruck, Austria
  • Institute of Molecular Medicine and Max-Planck-Research-Group on Stem Cell Aging, University of Ulm, 89081 Ulm, Germany
  • Johannes Gutenberg University Mainz (DE)
Corresponding author
Rudolph, K. Lenhard
ORCID
Venue
Aging
Publisher
Impact Journals, LLC
Published
2009-03-05
Volume
1
Issue
3
Pages
303-315
ISSN
1945-4589 (ISSN-L)
DOI
10.18632/aging.100030
PMC
PMC2830048
OpenAlex
W2144170687
Cited by
21
References
12
Citations by year
2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2013: 1 · 2012: 3
FWCI
2.44
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Deutsche Forschungsgemeinschaft
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 › Mitochondrial Function and Pathology
Keywords
manganese superoxide dismutase, haploinsufficiency, telomere dysfunction, telomere shortening, oxidative DNA damage, mitochondrial oxidative stress, cellular senescence, lifespan, stem cell depletion, antioxidant defense
MeSH terms
Superoxide Dismutase 2, Aging, Animals, Antioxidants, DNA Damage, Hematopoietic Stem Cells, Heterozygote, Longevity, Mitochondria, Superoxide Dismutase, Telomere, Cellular Senescence, Mice, Knockout, Oxidative Stress, Telomerase, Mice

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