Aerobic exercise training partially reverses the impairment of Nrf2 activation in older humans.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 32866619 · doi:10.1016/j.freeradbiomed.2020.08.016
What was done
Young (aged 18–28 years, n = 21) and older (aged ≥60 years, n = 19) men and women were randomized to an 8-week aerobic exercise training program (3 days/week, 45 minutes/day) or a non-exercise control group. Before and after the 8-week intervention, participants completed an acute exercise challenge (30 minutes of cycling at 70% VO2peak). Peripheral blood mononuclear cells (PBMCs) were collected at 7 timepoints (pre-exercise, +10 m, +30 m, +1 h, +4 h, +8 h, +24 h) to measure Nrf2 nuclear localization, GCLC protein, and gene expression of NQO1, HO1, and GCLC.
What was found
Prior to training, older adults had significantly higher basal Nrf2 levels (p = 0.004) and a blunted acute Nrf2 signaling response compared to young adults (p = 0.05). Exercise training decreased basal Nrf2 expression compared to control (p = 0.032) and improved the acute Nrf2 signaling response in both young and older participants (p < 0.05). Restoration of the Nrf2 signaling response correlated with the change in basal Nrf2 (p = 0.039), an effect driven by older adults (p = 0.014). Lower basal nuclear Nrf2 was associated with greater acute exercise responses in Nrf2 and GCLC protein and NQO1 and GCLC mRNA.
Why it matters
This study provides randomized evidence that age-related blunting of Nrf2 antioxidant signaling is modifiable, showing that 8 weeks of aerobic exercise partially restores dynamic cellular redox responses in sedentary older adults.
Limits
The total sample size was small (40 participants across four sub-groups). Outcomes were surrogate molecular markers measured only in circulating PBMCs rather than skeletal muscle or other primary metabolic tissues, and clinical functional outcomes were not reported in the abstract.
Cited by
- contradicts In young people, exercise increases NRF2 expression, whereas in people over 60, over-exercising causes NRF2 levels to decline.