Sulforaphane improves exercise-induced NRF2 signaling in older adults: an in vivo-ex vivo approach

Redox signaling is a key mechanism of exercise-induced adaptation. However, studies have demonstrated impaired responses to acute exercise in older organisms. Adjunctive therapies to augment exercise effects may overcome these deficits. Sulforaphane (SFN), a phytochemical from cruciferous vegetables, stimulates NRF2. This study tested the hypothesis that combining acute exercise (in vivo stimulus) with ex vivo SFN treatment would induce greater NRF2 activation and signaling in older adults compared to either treatment alone. Twenty-five older adults (12 men, 13 women; mean age: 67 ± 5 years) performed 30-min cycling exercise (AET). Blood was drawn before and immediately after the AET to isolate PBMCs and incubate with and without SFN (5 µM) treatment (four conditions: DMSO (CON), SFN, exercise (EX), and EX + SFN). PBMCs were harvested after 2-h or 5-h incubation for measures of NRF2 or gene expression for NQO1, HO-1, GR, and GCLC targets, respectively. All treatments (SFN, EX, EX + SFN) increased NRF2 activation compared to CON (p < 0.05). The response to EX + SFN was significantly greater than either SFN or EX alone (2.1-fold versus 1.5-fold, p = 0.01). SFN stimulation resulted in a significant upregulation of all four genes compared to control (p < 0.001). EX + SFN treatment stimulated a greater increase in gene expression compared to EX (p < 0.05); however, SFN did not differ statistically from EX + SFN, suggesting a possible ceiling effect of the SFN concentration in terms of gene expression. There were no significant sex differences in any of the responses. These data suggest that combining exercise with SFN may amplify the strength of NRF2/ARE redox signaling in older adults. ClinicalTrials.gov ID: NCT04848792.