Sulforaphane improves exercise-induced NRF2 signaling in older adults: an in vivo-ex vivo approach.
Level 3 - non-randomized controlled study
Single-arm within-subject controlled study combining in vivo exercise with ex vivo PBMC treatments.
PubMed 41099966 · doi:10.1007/s11357-025-01939-5
What was done
Twenty-five older adults (12 men, 13 women; mean age 67 ± 5 years) completed a 30-minute cycling exercise bout. Blood samples drawn before and immediately after exercise were used to isolate peripheral blood mononuclear cells (PBMCs). Cells were incubated ex vivo across four conditions: control (DMSO), sulforaphane (SFN, 5 µM), exercise alone (EX), and exercise plus SFN (EX + SFN). PBMCs were harvested after 2 hours to measure NRF2 activation and after 5 hours to quantify gene expression of NQO1, HO-1, GR, and GCLC.
What was found
All treatments (SFN, EX, EX + SFN) significantly increased NRF2 activation compared to control (p < 0.05). The EX + SFN condition produced a 2.1-fold increase in NRF2 activation, which was significantly greater than the 1.5-fold increase seen with either SFN or EX alone (p = 0.01). SFN exposure significantly upregulated all four antioxidant target genes compared to control (p < 0.001). While EX + SFN stimulated greater target gene expression than EX alone (p < 0.05), it did not differ significantly from SFN alone. No significant sex differences were observed.
Why it matters
These findings show that sulforaphane can augment exercise-induced NRF2 redox signaling in cells from older adults, providing a mechanistic basis for future trials testing oral sulforaphane alongside exercise in aging populations.
Limits
Sulforaphane was applied ex vivo to isolated blood cells rather than administered orally in vivo. The sample size was small (n = 25), measurements were restricted to circulating PBMCs rather than skeletal muscle tissue, and downstream antioxidant protein levels or functional clinical outcomes were not assessed.