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

Abstract

La inmunosenescencia implica cambios de reestructuración relacionados con la edad en las funciones inmunitarias innatas y adaptativas. Hemos sugerido que estos cambios del sistema inmunitario participan en la velocidad de envejecimiento al modular el proceso de oxi-inflamm-ageing. Así, las alteraciones relacionadas con la edad en la inmunidad pueden ser marcadores de edad biológica y predictores de longevidad. Se han observado diferencias de género en el estado de oxidación y en las funciones inmunes en ratas, con mayor oxidación e inmunosenescencia en los machos. Los estrógenos participan activamente en la modulación de la función inmune y su pérdida durante la transición menopáusica acelera el deterioro inmunitario. La ovariectomía en roedores constituye un modelo adecuado de pérdida de estrógenos humanos. En este trabajo se estudian funciones inmunes y parámetros inflamatorios y de estrés oxidativo en macrófagos y linfocitos peritoneales de hembras ancianas sometidas o no a ovariectomía y de machos de la misma edad, observándose que la pérdida de estrógenos hace que las hembras se asemejen a los machos, lo que apoya el papel protector de los estrógenos a lo largo del envejecimiento.

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.