Background: Redox imbalance, characterized by excess production of reactive oxygen species relative to antioxidant defenses, is a key mechanism underlying age- and disuse-related vascular dysfunction. Nuclear factor erythroid 2-related factor (Nrf2) is a master transcriptional regulator of cellular redox status, and dysregulated Nrf2 signaling is closely linked to vascular dysfunction. Therefore, we hypothesized that activation of the Nrf2 pathway with the phytochemical combination PB125 would 1) improve lower limb macro- and microvascular function in younger and older adults and 2) preserve macro- and microvascular function in younger and older adults following 2 weeks of limb immobilization (young) or 1 week of bed rest (old). Methods: Twenty (8M/12F) younger and twenty-four (12M/12F) older adults were randomized to consume either 200 mg/day of PB125 or Placebo for 3-4 weeks. All participants consumed PB125 or Placebo for 2 weeks and continued supplementation during the periods of disuse which included 2 weeks of limb immobilization for young adults and 1 week of bed rest for older adults. Assessments of macrovascular (popliteal flow-mediated dilation, POP-FMD) and microvascular (leg blood flow AUC LBFAUC and leg vascular conductance LVCAUC from passive leg movement) function were performed at baseline (V1), 2 weeks after supplementation (V2) and following the period of disuse (V3). Results: PB125 improved POP-FMD in older (V1: 1.5±1.5 to V2: 2.3±1.4 %, interaction p=0.032) but not younger (V1: 3.4±2.6 to V2: 4.4±2.8 %, interaction p=0.271) adults following 2 weeks of supplementation. PB125 did not improve LBFAUC or LVCAUC in younger or older adults following 2 weeks of supplementation (all, p>0.05). In response to 2 weeks of limb immobilization in younger adults, PB125 preserved POP-FMD (PB125: V2: 4.4±2.8 to V3: 3.3±1.8 %, p=0.302 vs PLACEBO: V2: 4.8±2.9 to V3: 2.5±1.7 %, p=0.032) but not LBFAUC or LVCAUC (both, p>0.05). Similarly, following 1 week of bed rest, PB125 preserved POP-FMD (PB125: V2: 2.3±1.4 to V3: 2.7±1.4 %, p=0.269 vs PLACEBO: V2: 1.4±1.1 to V3: 0.6±0.8 %, p=0.015) in older adults but not LBFAUC or LVCAUC (both, p>0.05). Conclusion: These findings indicate an age-dependent effect for targeted Nrf2 activation via PB125 in improving lower limb macrovascular function. Interestingly, despite the different experimental models of disuse and duration of each protocol, macrovascular function was preserved by targeted Nrf2 activation. Taken together, these results indicate that targeted Nrf2 activation confers vascular improvements with aging and mitigates vascular dysfunction following periods of disuse in both younger and older adults. Funding source: 5R01HL142603-05 (JDT), I01CX001999 (JDT) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Carlini et al. (Fri,) studied this question.