Ovariectomy shortens the life span of female mice

Abstract

// Valeria Benedusi 1 , Elisa Martini 2 , Marinos Kallikourdis 2, 3 , Alessandro Villa 1 , Clara Meda 1 , Adriana Maggi 1 1 Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133, Milan, Italy 2 Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy 3 Department of Medical Biotechnologies and Translational Medicine, University of Milan, 20089 Rozzano, Milan, Italy Correspondence to: Adriana Maggi, e-mail: adriana.maggi@unimi.it Keywords: female mammals, ovariectomy, life span, inflammation, estrogens Received: December 19, 2014      Accepted: December 19, 2014      Published: February 12, 2015 ABSTRACT This study shows that lack of ovarian activity has a negative impact on the life span of female mice. The extent to which this phenomenon could be associated with the anti-inflammatory effect of estrogens was analyzed in metabolic organs and aorta, by quantitative analysis of mRNAs encoding proteins in the inflammatory cascade. We demonstrate that the TNFα, IL-1β, MCP-1, MIP-2 and IL-6 mRNA contents are increased in the liver, adipose tissue and aorta 7 months after ovariectomy (ovx) and this increased basal inflammation is maintained as the mice aged. In contrast, the extent of inflammatory gene expression is directly proportional to age in sham-operated mice. As a consequence, at 22 months, most of the inflammatory parameters examined were higher in the sham-operated group compared with the ovx group. These observations led us to propose that the decreased longevity of ovx mice may be due to an acceleration of the basal state of inflammation in metabolic organs, which is likely driven by the combination of a lack of estrogen-mediated anti-inflammatory activity and the loss of gonadal control of energy metabolism.