Ovariectomy causes immunosenescence and oxi-inflamm-ageing in peritoneal leukocytes of aged female mice similar to that in aged males.

Immunosenescence involves age-associated restructuring changes of innate and adaptative immune functions. We have suggested that these changes of the immune system participate in the rate of ageing through modulating oxi-inflamm-ageing. Thus, age-related changes in the immune system can be biological age markers and predictors of longevity. Gender differences in oxidation status and immune functions have been observed in rats, with males showing higher oxidation and immunosenescence than females of the same age. Oestrogens are sex hormones that actively participate in modulating the mammalian immune function and, therefore, the age-related impairment of the immune response is drastically accelerated in females during the menopausal transition. Ovariectomy in rodents constitutes a good model for mimicking human oestrogen loss and thus the menopausal situation. Recently, we have shown the deleterious effects of oestrogen loss on several functions of leukocytes from immune organs in rats and mice. In addition, ovariectomised rats show similar levels in these immune functions to those in males. The present work studied several functions as well as inflammatory and oxidative stress parameters in mouse peritoneal macrophages and lymphocytes from old sham and ovariectomised females, as well as in males of the same age. In general, the results show that females, which have a higher immune response and a lower oxidation and inflammation than males, appear similar to males in the parameters studied when they have lost oestrogens by ovariectomy. Thus, these data support the positive role of oestrogens in the immune function through the ageing process.

Effects of growth hormone, melatonin, oestrogens and phytoestrogens on the oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio and lipid peroxidation in aged ovariectomized rats.

Ovariectomy constitutes a commonly used model in rats and mice for human menopause. After ovariectomy, an imbalance between oxidant production and antioxidant levels appears in favour of the former, with increased oxidative stress and consequently an acceleration of ageing. In the present work, the levels of reduced glutathione (GSH), a relevant antioxidant, and oxidized glutathione (GSSG), an oxidant compound, as well as lipid peroxidation (through malondialdehyde (MDA) levels), were studied in liver, heart, kidney and spleen homogenates of old (24 months of age) unovariectomized and ovariectomized female Wistar rats. The results showed a significant increase of the GSSG/GSH ratio, a marker of oxidative stress, and higher MDA production in all the studied organs of ovariectomized rats as compared with unovariectomized animals. These data confirm the idea that ovariectomy accelerates the ageing process. Administration of growth hormone (GH), melatonin (MEL) and oestrogens (OE), as well as soybean phytoestrogens (PE) for 10 weeks, between 22 and 24 months of age, was able to decrease oxidative stress in the investigated organs of ovariectomized old rats, therefore slowing down the ageing process in those animals.