title: The hallmarks of fibroblast ageing.
abstract: Ageing is influenced by the intrinsic disposition delineating what is maximally possible and extrinsic factors determining how that frame is individually exploited. Intrinsic and extrinsic ageing processes act on the dermis, a post-mitotic skin compartment mainly consisting of extracellular matrix and fibroblasts. Dermal fibroblasts are long-lived cells constantly undergoing damage accumulation and (mal-)adaptation, thus constituting a powerful indicator system for human ageing. Here, we use the systematic of ubiquitous hallmarks of ageing (Lopez-Otin et al., 2013, Cell 153) to categorise the available knowledge regarding dermal fibroblast ageing. We discriminate processes inducible in culture from phenomena apparent in skin biopsies or primary cells from old donors, coming to the following conclusions: (i) Fibroblasts aged in culture exhibit most of the established, ubiquitous hallmarks of ageing. (ii) Not all of these hallmarks have been detected or investigated in fibroblasts aged in situ (in the skin). (iii) Dermal fibroblasts aged in vitro and in vivo exhibit additional features currently not considered ubiquitous hallmarks of ageing. (iv) The ageing process of dermal fibroblasts in their physiological tissue environment has only been partially elucidated, although these cells have been a preferred model of cell ageing in vitro for decades.
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: Jean
authors.initials: J
authors.lastname: Krutmann
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; Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Haendeler
authors.affiliation: Center for Microbiology and Virology, Institute of Virology, Heinrich-Heine-University, Med. Faculty, D-40225 Düsseldorf, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Schaal
authors.affiliation: Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
authors.forename: Jens W
authors.initials: JW
authors.lastname: Fischer
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: Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany; Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Reinke
authors.affiliation: Department of Neuropathology, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.affiliation: Institute for Molecular Medicine, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany; Molecular Proteomics Laboratory, Centre for Biological and Medical Research (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Stühler
authors.affiliation: Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany; Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
authors.forename: Natascia
authors.initials: N
authors.lastname: Ventura
authors.affiliation: German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gundermann
authors.affiliation: German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Boukamp
authors.affiliation: Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany. Electronic address: boege@med.uni-duesseldorf.de.
authors.forename: Fritz
authors.initials: F
authors.lastname: Boege
mesh_terms: D000375:Aging; D016922:Cellular Senescence / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism; D015595:Skin Aging / Q000502:physiology*; D012879:Skin Physiological Phenomena
chemical_list: D046988:Proteasome Endopeptidase Complex
keywords: Altered proteostasis; Cellular senescence; DNA damage; Dermal fibroblasts; Extrinsic skin ageing; Mitochondrial dysfunction