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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Modulation of longevity-associated genes by estrogens or phytoestrogens

Jose Viña1 / Juan Sastre2 / Federico V. Pallardó3 / Juan Gambini4 / Consuelo Borrás5

1Departamento de Fisiología, Universidad de Valencia, E-46010 Valencia, Spain

2Departamento de Fisiología, Universidad de Valencia, E-46010 Valencia, Spain

3Departamento de Fisiología, Universidad de Valencia, E-46010 Valencia, Spain

4Departamento de Fisiología, Universidad de Valencia, E-46010 Valencia, Spain

5Fundación Investigación Hospital Clínico Universitario de Valencia, E-46010 Valencia, Spain

Corresponding author

Citation Information: Biological Chemistry. Volume 389, Issue 3, Pages 273–277, ISSN (Online) 14374315, ISSN (Print) 14316730, DOI: 10.1515/BC.2008.027, March 2008

Publication History

Published Online:


Females live longer than males. We have shown that the higher levels of estrogens in females protect them against aging, by up-regulating the expression of antioxidant, longevity-related genes, such as that of selenium-dependent glutathione peroxidase (GPx) and Mn-superoxide dismutase (Mn-SOD). Both estradiol and genistein (the most abundant phytoestrogen in soybeans) share chemical properties which confer antioxidant features to these compounds. However, the low concentration of estrogens and phytoestrogens make it unlikely that they exhibit significant antioxidant capacity in the organism. Physiological concentrations of estrogens and nutritionally relevant concentrations of genistein activate the MAP kinase pathway. These, in turn, activate the nuclear factor kappa B (NF-κB) signaling pathway. Activation of NF-κB by estrogens subsequently activates the expression of Mn-SOD and GPx, but genistein is only capable of activating Mn-SOD expression. This could be due to the fact that genistein binds preferably to estrogen receptor β. The antioxidant protection is reflected in the lower peroxide levels found in cells treated with estrogens or phytoestrogens when compared with controls. The challenge for the future is to find molecules that have the beneficial effects of estradiol, but without its feminizing effects. Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet this challenge.

Keywords: aging; antioxidant enzymes; estrogenic compounds; free radicals; gender; oxidative stress

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