Chronic in vivo exposure to glucocorticoids prolongs cellular lifespan: the case of Cushing's syndrome-patients' fibroblasts.
Glucocorticoid (GC) hypersecretion constitutes the major hormonal response to stress. In an effort to investigate the impact of a long-lasting exposure to high GC levels in vivo on cellular longevity, we have studied the lifespan of skin fibroblasts from patients suffering from Cushing's syndrome, who are characterised by chronic endogenous GC excess. Interestingly, we have observed that these cells exhibit a significant increase in their proliferative lifespan when cultured in vitro, under standard conditions, compared to fibroblasts from normal donors. In parallel, these cells secrete lower levels of transforming growth factor-beta, known to be implicated in stress-induced premature senescence. Furthermore, they also exhibit an intense stress reaction (near 2-fold, compared to normal cells) in terms of heat-shock protein-70 induction. These results support the hypothesis that stress response may have beneficial consequences in cellular longevity, as well as in tissue homeostasis.
Pratsinis
Harris
H
Laboratory of Cell Proliferation & Ageing, Institute of Biology, National Centre for Scientific Research, Demokritos, 153 10 Athens, Greece.
Tsagarakis
Stylianos
S
Zervolea
Irene
I
Giannakopoulos
Fivos
F
Stathakos
Dimitri
D
Thalassinos
Nikos
N
Kletsas
Dimitris
D
D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D003480:Cushing Syndrome / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005938:Glucocorticoids; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D013312:Stress, Physiological / Q000150:complications; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D005938:Glucocorticoids; D006360:Heat-Shock Proteins; D016212:Transforming Growth Factor beta