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Mech Ageing Dev. 2014 Jun;138:26-44. doi: 10.1016/j.mad.2014.03.004. Epub 2014 Mar 29.

The hallmarks of fibroblast ageing.

Author information

1
Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany.
2
Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany; Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
3
Center for Microbiology and Virology, Institute of Virology, Heinrich-Heine-University, Med. Faculty, D-40225 Düsseldorf, Germany.
4
Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
5
Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
6
Department of Neuropathology, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
7
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.
8
German Cancer Research Centre (DKFZ), Heidelberg, Germany.
9
Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany. Electronic address: boege@med.uni-duesseldorf.de.

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.

KEYWORDS:

Altered proteostasis; Cellular senescence; DNA damage; Dermal fibroblasts; Extrinsic skin ageing; Mitochondrial dysfunction

PMID:
24686308
DOI:
10.1016/j.mad.2014.03.004
[Indexed for MEDLINE]

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