Sex differences and effects of aerobic capacity on redox stress resilience in older men and women

Resistance to oxidative stress is reduced with age but there is lack of data regarding sex differences. In general, many sex differences are driven by sex hormones and thus might be expected to be lessened after menopause and at older ages. Aerobic fitness has been shown to increase redox capacity in older adults but whether adaptations differ between men and women is unknown. The aim of this study was to investigate sex differences and the association between redox capacity and aerobic fitness. Healthy men (n=20 and women (n=17) ages 60-86y participated in this study. Maximal oxygen consumption was measured with a graded exercise test on a cycle ergometer. Resistance to oxidative stress was measured by F₂-isoprostane (F₂-isoP) response to forearm ischemia/reperfusion (I/R) trial. The I/R trial elicited a significant F₂-isoP response in the cohort as a whole (p<0.05). Women had higher F₂-isoP levels across time compared to men and an earlier peak (p<0.05). When the data were analyzed as percent change from baseline, the time-by-sex interaction remained significant (p<0.01) but the group difference was no longer significant. Fitness levels were negatively correlated with both the overall F₂-isoP levels (AUC; r=-0.490) and the response with respect to baseline (AURC; r=-0.476) in women (p<0.05) but not in men. These data suggest that age and menopause-related increases in oxidative stress are greater in women relative to the expected age-related increase in men. Furthermore, women are more responsive to the effects of physical fitness on attenuating oxidative stress, possibly mediated by body composition.