Induction of cellular stress responses by phytochemicals for nutritional applications toward anti-aging intervention

Abstract

Aging is an important risk factor for the development of age-related diseases and is associated with decreased cellular antioxidant defenses. Under the scope of the undergoing NaturAge project, our group is currently investigating the ability of some plant extracts and isolated phytochemicals to induce antioxidant defenses through Nrf2/ARE signaling. That, will be associated with possible anti-aging effects using normal human skin fibroblasts undergoing aging in vitro. Recently, we have shown the ability of the polyphenol curcumin to induce cellular antioxidant defenses through induction of a stress response in normal human skin fibroblasts, affording protection from a further oxidant challenge with tert-BOOH [1]. Curcumin incubation for 24h induced heme oxygenase-1 (HO-1) protein levels, GST activity, GSH levels and GSH/GSSG ratio. These effects were preceded by induction of oxidative stress as shown by increased levels of ROS and DNA damage, and impairment of the cells’ GSH redox state. The induction of antioxidant defenses in human fibroblasts was shown to be redox and PI3K/Akt dependent [1]. In conclusion, these results support the view that phytochemical-induced hormetic stimulation of cellular antioxidant defenses can be a useful approach toward anti-aging intervention. [1] Lima CF, Pereira-Wilson C, Rattan SIS (2011). Mol. Nutr. Food Res., 55: 430-42. Acknowledgements: ACC is supported by BI1-PTDC/QUI-BIQ/101392/2008 grant. This work is supported by FCT research grant NaturAge – PTDC/QUI-BIQ/101392/2008.