Why females live longer than males?: Importance of the upregulation of longevity-associated genes by oestrogenic compounds

Females live longer than males in many mammalian species, including humans. Mitochondria from females produce approximately half the amount of H2O2 than males. We have found that females behave as double transgenics overexpressing both superoxide dismutase and glutathione peroxidase. This is due to oestrogens that act by binding to the estrogen receptors and subsequently activating the mitogen activated protein (MAP) kinase and nuclear factor kappa B (NF-κ B) signalling pathways. Phyloestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of upregulating antioxidant genes, by hormonal and dietary manipulations, in order to increase longevity is discussed. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.