title: Proteome-wide analysis reveals an age-associated cellular phenotype of in situ aged human fibroblasts.
abstract: We analyzed an ex vivo model of in situ aged human dermal fibroblasts, obtained from 15 adult healthy donors from three different age groups using an unbiased quantitative proteome-wide approach applying label-free mass spectrometry. Thereby, we identified 2409 proteins, including 43 proteins with an age-associated abundance change. Most of the differentially abundant proteins have not been described in the context of fibroblasts' aging before, but the deduced biological processes confirmed known hallmarks of aging and led to a consistent picture of eight biological categories involved in fibroblast aging, namely proteostasis, cell cycle and proliferation, development and differentiation, cell death, cell organization and cytoskeleton, response to stress, cell communication and signal transduction, as well as RNA metabolism and translation. The exhaustive analysis of protein and mRNA data revealed that 77 % of the age-associated proteins were not linked to expression changes of the corresponding transcripts. This is in line with an associated miRNA study and led us to the conclusion that most of the age-associated alterations detected at the proteome level are likely caused post-transcriptionally rather than by differential gene expression. In summary, our findings led to the characterization of novel proteins potentially associated with fibroblast aging and revealed that primary cultures of in situ aged fibroblasts are characterized by moderate age-related proteomic changes comprising the multifactorial process of aging.
authors.affiliation: Institute for Molecular Medicine, Heinrich-Heine-University, Düsseldorf, Germany. Molecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Waldera-Lupa
authors.affiliation: Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
authors.forename: Faiza
authors.initials: F
authors.lastname: Kalfalah
authors.affiliation: Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Florea
authors.affiliation: Institute of Computational Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Sass
authors.affiliation: Institute for Molecular Medicine, Heinrich-Heine-University, Düsseldorf, Germany. Molecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Kruse
authors.affiliation: Institute for Molecular Medicine, Heinrich-Heine-University, Düsseldorf, Germany. Molecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Rieder
authors.affiliation: Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Tigges
authors.affiliation: Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Fritsche
authors.affiliation: Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.affiliation: Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Freiburg, Germany. German Cancer Consortium (DKTK), Freiburg, Germany. German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Busch
authors.affiliation: Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Freiburg, Germany. German Cancer Consortium (DKTK), Freiburg, Germany. German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Boerries
authors.affiliation: Department of Biomedical Research, Leibniz-Institute for Analytical Science - ISAS, Dortmund, Germany.
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.affiliation: Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Boege
authors.affiliation: Department of Mathematics, Technical University Munich, Garching, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Theis
authors.affiliation: Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.affiliation: Institute for Molecular Medicine, Heinrich-Heine-University, Düsseldorf, Germany. Molecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Stühler
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D035683:MicroRNAs; D008875:Middle Aged; D010641:Phenotype; D040901:Proteomics; D059467:Transcriptome; D055815:Young Adult
chemical_list: D035683:MicroRNAs