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Resveratrol, but not dihydroresveratrol, induces premature senescence in primary human fibroblasts

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Abstract

Resveratrol, trans-3,5,4′-trihydroxystilbene, is a polyphenolic compound which has been reported to mimic the gene expression patterns seen in whole animals undergoing dietary restriction. The mechanism of action of resveratrol remains poorly understood, but modulation of both cellular proliferation and apoptosis has been proposed as important routes by which the molecule may exert its effects. This study reports the effects of both resveratrol and dihydroresveratrol (a primary in vivo metabolite) on the proliferative capacity of human primary fibroblasts. No generalised reduction in the growth fraction was observed when fibroblasts derived from three different tissues were treated with resveratrol at concentrations of 10 μm or less. However, concentrations above 25 μm produced a dose-dependent reduction in proliferation. This loss of the growth fraction was paralleled by an increase in the senescent fraction as determined by staining for senescence associated beta galactosidase and dose recovery studies conducted over a 7-day period. Entry into senescence in response to treatment with resveratrol could be blocked by a 30-min preincubation with the p38 MAP kinase inhibitor SB203580. No effects on proliferation were observed when cells were treated with dihydroresveratrol at concentrations of up to 100 μm.

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Acknowledgements

The authors would like to acknowledge the support of Research into Ageing, the Biotechnology and Biological Sciences Research Council, and the EPSRC/BBSRC Strategic Promotion of Ageing Research Capacity (SPARC) network. Also we would like to acknowledge the support of the Glen Foundation for Medical Research in addition to our other research sponsors.

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Authors and Affiliations

  1. School of Pharmacy and Biomolecular Sciences, Cockcroft Building, University of Brighton, Lewes Road, Moulsecoomb, Brighton, East Sussex, UK

    Richard G. A. Faragher, Patricia Majecha, Noel S. Y. Fong, Angela Sheerin & Elizabeth L. Ostler

  2. Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA

    Dominic G. A. Burton

  3. Department of Pathology, School of Medicine, University of Cardiff, Heath Park, Cardiff, Wales, UK

    Terence Davis

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  1. Richard G. A. Faragher
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  2. Dominic G. A. Burton
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  3. Patricia Majecha
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  4. Noel S. Y. Fong
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  5. Terence Davis
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  6. Angela Sheerin
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  7. Elizabeth L. Ostler
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Correspondence to Richard G. A. Faragher.

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Faragher, R.G.A., Burton, D.G.A., Majecha, P. et al. Resveratrol, but not dihydroresveratrol, induces premature senescence in primary human fibroblasts. AGE 33, 555–564 (2011). https://doi.org/10.1007/s11357-010-9201-5

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  • DOI: https://doi.org/10.1007/s11357-010-9201-5

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