Modulation of longevity-associated genes by estrogens or phytoestrogens.
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-kappa B) signaling pathway. Activation of NF-kappa B 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 beta. 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.
Viña
Jose
J
Departamento de Fisiología, Universidad de Valencia, E-46010 Valencia, Spain. jose.vina@uv.es
Sastre
Juan
J
Pallardó
Federico V
FV
Gambini
Juan
J
Borrás
Consuelo
C
D000818:Animals; D000975:Antioxidants / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008136:Longevity / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics; D015854:Up-Regulation
D000975:Antioxidants; D004967:Estrogens; D005609:Free Radicals; D048789:Phytoestrogens; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase