UVB-Induced Senescence of Human Dermal Fibroblasts Involves Impairment of Proteasome and Enhanced Autophagic Activity

In the current study, we have extended previous findings aiming at a better understanding of molecular mechanisms underlying UVB-induced senescence of diploid human dermal fibroblasts (HDFs), an experimental model to study the process of photoaging in the skin. We provide evidence that the inhibitio...

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Published inThe journals of gerontology. Series A, Biological sciences and medical sciences Vol. 72; no. 5; p. 632
Main Authors Cavinato, Maria, Koziel, Rafal, Romani, Nikolaus, Weinmüllner, Regina, Jenewein, Brigitte, Hermann, Martin, Dubrac, Sandrine, Ratzinger, Gudrun, Grillari, Johannes, Schmuth, Matthias, Jansen-Dürr, Pidder
Format Journal Article
LanguageEnglish
Published United States 01.05.2017
Subjects
Autophagy - radiation effects
Blotting, Western
Cell Proliferation - radiation effects
Cells, Cultured
Cellular Senescence - radiation effects
Dose-Response Relationship, Radiation
Fibroblasts - radiation effects
Humans
Proteasome Endopeptidase Complex - radiation effects
Radioimmunoprecipitation Assay
Reactive Oxygen Species - metabolism
Real-Time Polymerase Chain Reaction
Skin Aging - radiation effects
Ultraviolet Rays
UVB
Senescence
Skin aging
Autophagy
Proteasome
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Summary:In the current study, we have extended previous findings aiming at a better understanding of molecular mechanisms underlying UVB-induced senescence of diploid human dermal fibroblasts (HDFs), an experimental model to study the process of photoaging in the skin. We provide evidence that the inhibition of proteasomal degradation of damaged proteins and the activation of autophagosome formation are early events in UVB-induced senescence of HDFs, dependent on UVB-induced accumulation of reactive oxygen species. Our data suggest that autophagy is required for the establishment of the senescent phenotype in UVB-treated HDFs and that inhibition of autophagy is sufficient to change the cell fate from senescence to cell death by apoptosis. Studies in reconstructed skin equivalents revealed that UVB irradiation triggers hallmarks of autophagy induction in the dermal layer. These findings have potential implications for fundamental as well as translational research into skin aging, in particular photoaging.
ISSN:1758-535X
DOI:10.1093/gerona/glw150