The hallmarks of fibroblast ageing

• Extrinsic skin ageing converges on the dermis consisting of fibroblasts and matrix.
• Dermal fibroblasts are long lived cells undergoing age-associated damage accumulation.
• Dermal fibroblasts aged in vitro exhibit most of the ubiquitous hallmarks of ageing.
• Dermal fibroblasts aged in situ recapitulate not all features of cellular senescence induced in vitro.
• Dermal fibroblast ageing in vitro and in vivo encompasses additional features currently not considered ubiquitous hallmarks of ageing.

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.