title: The unexpected anabolic phenotype and extended longevity of skin fibroblasts after chronic glucocorticoid excess.
abstract: Intense stress can challenge tissue homeostasis and accelerate the ageing process. However, several lines of evidence indicate that repeated mild stresses can have beneficial and even life-prolonging effects. Hypersecretion of glucocorticoids (GC) represents the major hormonal response to stress. Besides its life-sustaining role, GC excess, usually due to several side-effects that promote a "catabolic" phenotype, can be detrimental for several tissues. Cushing's syndrome patients are characterized by chronic endogenous GC excess and consequently at the time of diagnosis they have an atrophic elderly-like skin. Interestingly, when Cushing's syndrome fibroblasts were removed from the high-GC milieu in vivo and cultured in vitro under standard conditions they express an "anabolic" phenotype, i.e. they restore their ability for collagen synthesis, they secrete reduced levels of metalloproteases (MMP-1 and MMP-2) and have an increased proliferative capacity and contractility. Furthermore, these cells exhibit a significant extension of their proliferative lifespan, while they respond better to exogenous stress by producing significantly higher levels of heat-shock protein-70 (HSP70). These results imply that long-term hypercortisolism in vivo can have beneficial consequences on fibroblast physiology in vitro.
authors.affiliation: Laboratory of Cell Proliferation and Ageing, Institute of Biology, National Centre for Scientific Research Demokritos, Athens, Greece.
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.forename: Stylianos
authors.initials: S
authors.lastname: Tsagarakis
authors.forename: Irene
authors.initials: I
authors.lastname: Zervolea
authors.forename: Dimitri
authors.initials: D
authors.lastname: Stathakos
authors.forename: Nikos
authors.initials: N
authors.lastname: Thalassinos
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kletsas