Cited by 5Telomeres, Telomerase, and SenescenceT-cell and B-cell ImmunologyGenetics, Aging, and Longevity in Model Organisms

SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures

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Marthandan, Shiva, Freeburn, Robin, Steinbrecht, Susanne, Pawelec, Graham, Barnett, Yvonne·2014·Immunity & Ageing

Abstract

BACKGROUND: Damage to T cells of the immune system by reactive oxygen species may result in altered cell function or cell death and thereby potentially impact upon the efficacy of a subsequent immune response. Here, we assess the impact of the antioxidants Ebselen and N-acetyl cysteine on a range of biological markers in human T cells derived from a SENIEUR status donor. In addition, the impact of these antioxidants on different MAP kinase pathways in T cells from donors of different ages was also examined. METHODS: T cell clones were derived from healthy 26, 45 and SENIEUR status 80 year old people and the impact of titrated concentrations of Ebselen or N-acetyl cysteine on their proliferation and in vitro lifespan, GSH:GSSG ratio as well as levels of oxidative DNA damage and on MAP kinase signaling pathways was examined. RESULTS: In this investigation neither Ebselen nor N-acetyl cysteine supplementation had any impact on the biological endpoints examined in the T cells derived from the SENIEUR status 80 year old donor. This is in contrast to the anti-immunosenescent effects of these antioxidants on T cells from donors of 26 or 45 years of age. The analysis of MAP kinases showed that pro-apoptotic pathways become activated in T cells with increasing in vitro age and that Ebselen or N-acetyl cysteine could decrease activation (phosphorylation) in T cells from 26 or 45 year old donors, but not from the SENIEUR status 80 year old donor. CONCLUSIONS: The results of this investigation demonstrate that the biological phenotype of SENIEUR status derived human T cells negates the anti-immunosenescence effects of Ebselen and also N-acetyl cysteine. The results highlight the importance of pre-antioxidant intervention evaluation to determine risk-benefit.

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  • The antioxidant effects on T cell clones were not replicated in T cell clones from an elderly donor despite conforming to SENIEUR protocol criteria.

    “Critically, these effects were not replicated in T cell clones from an elderly donor (Marthandan et al. 2014) despite conforming to SENIEUR protocol criteria (Ligthart et al. 1984, 1990)”

    From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Marthandan et al. 2014

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Authors
Marthandan, S., Freeburn, R., Steinbrecht, S., Pawelec, G., & Barnett, Y.
Affiliations
  • Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
  • University of the West of Scotland (GB)
  • University of Tübingen (DE)
  • Nottingham Trent University (GB)
Corresponding author
Marthandan, Shiva
Venue
Immunity & Ageing
Published
2014-11-30
Volume
11
Issue
1
Pages
17-17
ISSN
1742-4933 (ISSN-L)
OpenAlex
W2158199059
Cited by
5
References
47
Citations by year
2019: 1 · 2017: 1 · 2016: 2 · 2015: 1
FWCI
0.89
Type
journal article
Language
en
Open access
Locations
  • Immunity & Ageing (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (acceptedVersion)
  • Anglia Ruskin Research Online (Anglia Ruskin University) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
Funders
  • University of Sussex
  • Bundesministerium für Bildung und Forschung (0315581)
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
immunosenescence, ebselen, N-acetylcysteine, antioxidants, T cells, reactive oxygen species, oxidative DNA damage, glutathione, MAPK signaling, apoptosis, T cell proliferation, donor age

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