[Molecular mechanisms of aging and its prevention by hormonal treatment in rats]

In two previous communications to the RANM four and two years ago, some data were shown supporting the role of GH, Melatonin and Estrogens in the prevention of aging in a group of physiological parameters including bone, liver metabolism and vascular activity, the Central nervous System (CNS,) the immune system and the skin. In the present work data about the molecular mechanisms involved will be presented. A total of 140 male and female rats have been submitted to different treatments over 10 weeks, between 22 and 24 months of age. Males have been treated with GH and Melatonin. Females were divided in two groups: intact and castrated at 12 months of age. The first group was treated with GH and Melatonin and the second with these two and additionally with Estradiol and Phytosoya. Aging was associated with a reduction in the number of neurones of the Hylus of the dentate gyrus of the hypothalamus and with a reduction of neurogenesis. GH treatment increased the number of neurones but did not increase neurogenesis thus suggesting a reduction of apoptosis. This was supported by the reduction in nucleosomes and the increase in Bcl2 observed in cerebral homogenates together with an increase in sirtuin2 and a reduction of caspases. Melatonin, estrogens and phytosoya treatments increased neurogenesis but did not enhanced the total number of neurones. On the liver, aging induced a signi-ficant increase in mitochondrial nitric oxide, an increase in cytochrome C in the cytosolic fraction and a reduction in the mitochondrial fraction thus inducing apoptosis as confirmed by the increase in caspases. Treatment for 2.5 months of old rats with GH and melatonin were able to significantly reduce the enhanced and increase the reduced values reducing apoptosis. A reduction in glutathione peroxidase and glutathione S-transferase was found also in old control rats when compared with the group of young animals. Keratinocytes from old rats in culture showed an increase in nucleosomes and a reduction in Bcl2 that was restored with GH and Melatonin. In conclusion, the mentioned hormonal treatment seems to have beneficial effects against age-induced damage in the CNS the liver and the skin through molecular mechanisms reducing oxidative stress and apoptosis.