Exercise Training Restores Age-impaired Nrf2 Signaling And Redox Capacity: 2462 Board #8 May 29 9:30 AM - 11:30 AM

PURPOSE: Nuclear erythroid-2-p45-related factor 2 (Nrf2) is an inducible transcription factor and the master regulator of antioxidant defenses. We have previously shown that older men have blunted Nrf2 signaling in response to a single exercise stimulus, compared to young. The present RCT tested the hypothesis that moderate exercise training would improve Nrf2 signaling in older, inactive individuals and this would translate to greater redox capacity against non-exercise oxidative stress challenge. METHODS: Young (18-28y, n=21) and older (≥60y, n=24) men and women were randomized to an 8-week aerobic exercise intervention (EX) or a non-exercise control group (CON). EX performed supervised aerobic exercise 3d/wk for 45-min/d. VO2peak was measured on a cycle ergometer. Nrf2 nuclear localization and GCLC protein were measured in response to acute exercise (30-min cycling at 70% VO2peak) in peripheral blood mononuclear cells at 7 time points (Pre, +10m, +30m, +1h, +4h, +8h, +24h). Plasma F2 isoprostanes were measured in response to forearm ischemia-reperfusion (I/R trial) as a marker of redox capacity. All measures were performed pre- and post-intervention RESULTS: EX improved VO2peak by 15%, while CON did not change (p<0.001), with no differences between age-groups or sexes. Nrf2 signaling response to acute exercise increased in EX compared to CON (p<0.001), in both young and older, in support of aerobic exercise restoring Nrf2 signaling in previously inactive individuals. GCLC protein content was increased in EX with no change in CON (p=0.03). Interestingly, CON had higher basal levels of nuclear Nrf2 after the intervention but did not respond to the acute stimulus indicating impaired signaling responses. Redox capacity was improved in EX compared to CON (p<0.05) as shown by lower F2-isoP responses to the I/R trial. Furthermore, there was a significant association between improvements in VO2peak and improvements in the I/R response (r =-0.46, p<0.01). CONCLUSION: To our knowledge, this is the first study to show increased Nrf2 activation in healthy humans, in response to an exercise intervention. These data support our hypothesis and demonstrate that older individuals can improve their cell signaling in response to exercise and systemic response to a non-exercise oxidative challenge.