Laboratory of Cell Proliferation and Ageing, Institute of Biology, National Centre for Scientific Research Demokritos, Athens, Greece.
Dose Response. 2006 Aug 19;4(2):133-44. doi: 10.2203/dose-response.05-007.Pratsinis.
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.
强烈的压力会挑战组织内环境平衡并加速衰老过程。然而,有几条证据表明,反复的轻度压力可能会产生有益的甚至延长寿命的效果。糖皮质激素(GC)的过度分泌是应激的主要激素反应。GC 过量除了维持生命的作用外,通常由于促进“分解代谢”表型的多种副作用,对几种组织都是有害的。库欣综合征患者的特点是慢性内源性 GC 过量,因此在诊断时,他们的皮肤呈现出萎缩的老年样外观。有趣的是,当库欣综合征成纤维细胞从体内高 GC 环境中被去除,并在标准条件下在体外培养时,它们表现出“合成代谢”表型,即它们恢复了胶原蛋白合成的能力,它们分泌的金属蛋白酶(MMP-1 和 MMP-2)水平降低,增殖能力和收缩性增加。此外,这些细胞的增殖寿命显著延长,而它们通过产生更高水平的热休克蛋白-70(HSP70)对外源应激的反应更好。这些结果表明,体内长期的高皮质醇血症对成纤维细胞的体外生理学可能有有益的影响。