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Dicarbonyl-induced accelerated aging in vitro in human skin fibroblasts

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Abstract

Dicarbonyls glyoxal (GO) and methylglyoxal (MGO) produced during the autoxidation of reducing sugars are a source of macromolecular damage in cells. Since an accumulation of damaged macromolecules is a universal characteristic of aging, we have tested whether GO and MGO which cause oxidative damage to proteins and other macromolecules can bring about accelerated aging in normal human skin fibroblasts in vitro. A treatment of cells with 1.0 mM GO or 400 μM MGO leads to the appearance of senescent phenotype within 3 days, as judged by the following criteria: morphological phenotype, irreversible growth arrest and G2 arrest, increased senescence-associated β-galactosidase (SABG) activity, increased H2O2 level, increased Nξ-(carboxymethyl)-lysine (CML) protein level, and altered activities of superoxide dismutase and catalase antioxidant enzymes. This experimental model of accelerated cellular aging in vitro can be useful for studies on testing the effects of various physical, chemical and biological conditions, including natural and synthetic molecules, for the modulation of aging.

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Acknowledgments

We thank Dr. Peter Kristensen for his interest and useful suggestions made during the course of these studies. Thanks to Helle Jakobsen and Gunhild Siboska for their technical assistance; to Alexander Schmitz for help in the FACS analysis; and to Cristovao Lima for performing the comet assay. The Laboratory of Cellular Ageing is supported by research grants from the Danish Medical Research Council (FSS), and EU’s Biomed Health Programme, Proteomage.

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  1. Henrik Sejersen

    Present address: Department of Animal Health, Welfare and Nutrition, Faculty of Agricultural Sciences, University of Aarhus, 8830, Tejle, Denmark

Authors and Affiliations

  1. Laboratory of Cellular Ageing, Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10-C, 8000, Aarhus, Denmark

    Henrik Sejersen & Suresh I. S. Rattan

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  1. Henrik Sejersen
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  2. Suresh I. S. Rattan
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Correspondence to Suresh I. S. Rattan.

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Sejersen, H., Rattan, S.I.S. Dicarbonyl-induced accelerated aging in vitro in human skin fibroblasts. Biogerontology 10, 203–211 (2009). https://doi.org/10.1007/s10522-008-9172-4

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  • DOI: https://doi.org/10.1007/s10522-008-9172-4

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