In old age, female prematurely aging mice - who show lower antioxidant defenses than their controls in adulthood - reach similar defense levels but maintain higher oxidation

INTRODUCTION: Adult prematurely aging mice (PAM), identified by their altered stress response, exhibit higher oxidative stress in leukocytes and shorter lifespan than non-prematurely aging mice (NPAM). It is unknown whether these differences persist with advancing age. The aim of this study was to evaluate antioxidant defenses related to the glutathione cycle in organs such as the spleen, heart, and liver of PAM and NPAM at different ages, as well as hepatic oxidative stress. MATERIALS AND METHODS: Six groups of female Swiss mice (N=10) were used: PAM and NPAM at adult (7 months), mature (13 months), and old (17 months) ages. Spleen, heart, and liver were collected to analyze total glutathione (TG), glutathione peroxidase (GPx), and glutathione reductase (GR). In the liver, reduced glutathione (GSH), oxidized glutathione (GSSG), the GSSG/GSH ratio, catalase (CAT) antioxidant activity, and xanthine oxidase (XO) oxidant activity were also measured. RESULTS: Adult PAM showed lower antioxidant defenses than NPAM across all organs. These differences diminished at the mature age and disappeared in old age. In the liver, PAM maintained lower GPx activity in old age, but at all ages displayed higher XO activity, higher GSSG levels, and an increased GSSG/GSH ratio compared with NPAM. CONCLUSION: Female adult PAM exhibit reduced antioxidant defenses compared with NPAM, but these differences fade with aging. The persistence of elevated hepatic oxidative stress in PAM may contribute to their reduced lifespan.