The hallmarks of fibroblast ageing

被引:174
作者
Tigges, Julia [1 ]
Krutmann, Jean [1 ]
Fritsche, Ellen [1 ]
Haendeler, Judith [1 ,2 ]
Schaal, Heiner [3 ]
Fischer, Jens W. [4 ]
Kalfalah, Faiza [2 ]
Reinke, Hans [1 ,2 ]
Reifenberger, Guido [5 ]
Stuehler, Kai [6 ,7 ]
Ventura, Natascia [1 ,2 ]
Gundermann, Sabrina [8 ]
Boukamp, Petra [8 ]
Boege, Fritz [2 ]
机构
[1] Leibniz Res Inst Environm Med IUF, Dusseldorf, Germany
[2] Univ Dusseldorf, Fac Med, Inst Clin Chem & Lab Diagnost, Dusseldorf, Germany
[3] Univ Dusseldorf, Ctr Microbiol & Virol, Inst Virol, D-40225 Dusseldorf, Germany
[4] Univ Dusseldorf, Fac Med, Inst Pharmacol & Clin Pharmacol, Dusseldorf, Germany
[5] Univ Dusseldorf, Dept Neuropathol, Fac Med, Dusseldorf, Germany
[6] Univ Dusseldorf, Inst Mol Med, Fac Med, Dusseldorf, Germany
[7] Univ Dusseldorf, Mol Prote Lab, Ctr Biol & Med Res BMFZ, Dusseldorf, Germany
[8] German Canc Res Ctr, Heidelberg, Germany
关键词
Dermal fibroblasts; Extrinsic skin ageing; Mitochondrial dysfunction; DNA damage; Altered proteostasis; Cellular senescence; HUTCHINSON-GILFORD-PROGERIA; EPIDERMAL-GROWTH-FACTOR; DNA-DAMAGE-RESPONSE; SENESCENCE-ASSOCIATED ALTERATIONS; ELEGANS MITOCHONDRIAL MUTANTS; INDUCED PREMATURE SENESCENCE; CIRCADIAN AUTOPHAGY RHYTHM; HUMAN-DIPLOID FIBROBLASTS; HUMAN DERMAL FIBROBLASTS; STRAND-BREAK REPAIR;
D O I
10.1016/j.mad.2014.03.004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:26 / 44
页数:19
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