Importancia del estrés oxidativo en la diferencia de longevidad entre machos y hembras

Résumé

Females live longer than males in many species, including humans. This can be explained on the basis of the mitochondrial theory of aging. We have investigated the differential mitochondrial oxidative stress between males and females to understand the molecular mechanisms enabling females to live longer than males. Mitochondria are a major source of free radicals in cells. Those from female rats generate half the amount of peroxides than those of males. Mitochondria from females have higher levels of reduced glutathione than those from males. Oxidative damage to mitochondrial DNA in males is four fold higher than that of females. This is due to a higher expression and activities of Mn-superoxide dismutase and of glutathione peroxidase in females, which behave as double transgenics overexpressing superoxide dismutase, and glutathione peroxidase, conferring protection against free radical mediated damage in aging. Moreover, 16S rRNA expression, which decreases significantly with aging, is four times higher in mitochondria from females than in those from males of the same chronological age. Studies in vitro show that oestradiol is an antioxidant, but that estrogenic effects must be transcriptional, by inducing the antioxidant enzyme gene expression. The facts reported here provide molecular evidence to explain the different life span in males and females. 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.