Curcumin-induced hormetic effects in human skin fibroblasts : implications toward anti-ageing interventions

Abstract

Ageing is associated with decreased cellular antioxidant defenses and with reduced ability to induce stress responses. We have tested the curcumin-induced hormetic stimulation of cellular stress responses in normal human skin fibroblasts, and associate those with potential anti-ageing effects. Curcumin incubation for 24h induced heme oxygenase-1 (HO-1) protein levels, GST activity, GSH levels and GSH/GSSG ratio. These effects were preceded in the first hours of incubation by induction of oxidative stress as shown by increased levels of ROS and DNA damage, and impairment of cells’ GSH redox state. The curcumin-induced increase in antioxidant defenses was shown to be redox and PI3K/Akt-dependent in human fibroblasts. The induction of this stress response led to protective hormetic effects via a further oxidant challenge with tert-BOOH. Replicative senescent cells possessed already higher HO-1 levels, and induction of HO-1 by curcumin was considerably impaired. In conclusion, the induction of stress responses by curcumin in human skin fibroblasts, which resulted in protection against a subsequent stressor, supports the view that phytochemical-induced hormetic stimulation of cellular antioxidant defenses can be a useful approach toward anti-aging intervention. Acknowledgements: This work is supported by FCT research grant NaturAge – PTDC/QUI-BIQ/101392/2008, which is co-funded by the program COMPETE from QREN with co-participation from the European Community fund FEDER.