Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany.
Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany; Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Düsseldorf, Germany.
Mech Ageing Dev. 2014 Jun;138:26-44. doi: 10.1016/j.mad.2014.03.004. Epub 2014 Mar 29.
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.
衰老是由内在的倾向性决定的，这种倾向性描绘了什么是最大可能的，而外在的因素则决定了这个框架是如何被个体利用的。内在和外在的衰老过程作用于真皮，真皮是一个有丝分裂后皮肤的隔室，主要由细胞外基质和成纤维细胞组成。真皮成纤维细胞是长寿细胞，不断经历着损伤的积累和（不适宜的）适应，因此构成了人类衰老的一个强大的指示系统。在这里，我们使用普遍存在的衰老标志系统（Lopez-Otin 等人，2013，Cell 153）来对有关真皮成纤维细胞衰老的现有知识进行分类。我们将可在培养中诱导的过程与皮肤活检或老年供体的原代细胞中出现的现象区分开来，得出以下结论：（i）在培养中衰老的成纤维细胞表现出大多数已建立的、普遍存在的衰老标志。（ii）并非所有这些标志都在原位（在皮肤中）衰老的成纤维细胞中被检测到或研究过。（iii）在体外和体内衰老的真皮成纤维细胞表现出目前不被认为是普遍存在的衰老标志的其他特征。（iv）尽管这些细胞几十年来一直是体外细胞衰老的首选模型，但真皮成纤维细胞在其生理组织环境中的衰老过程仅部分阐明。
