No association between changes in PBMC mitochondrial bioenergetics and cutaneous microvascular function after supplementation with a mitochondrial antioxidant

BACKGROUND: Peripheral blood mononuclear cells (PBMCs) have emerged as a common cellular model for investigating the mechanisms of vascular endothelial dysfunction. Mitochondrial dysfunction has been implicated as having a role in age-related vascular dysfunction, and supplementation with a mitochondria-specific antioxidant (MitoQ) improves endothelial function in older adults. However, there has yet to be an investigation of the effects of MitoQ supplementation on mitochondrial bioenergetics in PBMCs, or whether MitoQ-induced changes in PBMC mitochondrial function are related to changes in endothelial function in older adults. The primary aim of this study was to assess the effects of 6-weeks of MitoQ supplementation on PBMC mitochondrial function. A secondary aim was to evaluate the relation between changes in PBMC mitochondrial function and cutaneous microvascular function. METHODS: Ten older adults (66±3 yrs) were tested after 6 weeks of supplementation with MitoQ (20 mg/day) and a matched placebo in a randomized, counterbalanced fashion with a 4-week washout period. High-resolution respirometry and fluorometry measured PBMC mitochondrial respiration rate (JO 2 ) and membrane potential (Δψm), respectively, in response to substrate provision (pyruvate/glutamate/malate/succinate; PGMS) and a bioenergetic creatine kinase (CK) clamp at physiological ATP:ADP ratios (PCr1, PCr2, and PCr3). Mitochondrial reactive oxygen species (mtROS) emission was measured as hydrogen peroxide (H 2 O 2 ) emission, and production was quantified using inhibitors of glutathione reductase and thioredoxin/peroxiredoxin. Antioxidant buffering capacity (AoxBC) was calculated as the percentage of H 2 O 2 produced but not emitted. Cutaneous microvascular endothelial function was evaluated using intradermal microdialysis and a standard local heating (42°C) protocol to induce cutaneous vasodilation. After attaining a stable elevated blood flow plateau, 15 mM NG-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor) was infused to quantify the NO contribution to the vasodilation response. Laser-Doppler flowmetry (LDF) measured red cell flux and cutaneous vascular conductance (CVC = LDF/mean arterial pressure) and was normalized to maximal (%CVCmax; 28 mM sodium nitroprusside + 43°C local heating). JO 2 and Δψm were analyzed using 2-way ANOVA to assess treatment (MitoQ vs Placebo) and phase (PCr1, PCr2, and PCr3) effects. Paired t-tests were used to assess differences mtROS emission and production. Simple linear regression analyses assessed the relations between changes in PBMC mitochondrial bioenergetic variables and cutaneous microvascular responses to local heating. RESULTS: The Δψm was improved after 6 weeks of MitoQ supplementation compared with placebo at all phases PCr1, PCr2, and PCr3, p < 0.0001, but JO 2 (p = 0.89, p = 0.50, p = 0.20), mtROS emission and production p = 0.29 and p = 0.38, and AoxBC (p = 0.98) were not significant. Changes in, Δψm, and AoxBC in PBMCs were not associated with changes in the magnitude of the cutaneous microvascular response to local heating (p = 0.15) or the NO-contribution to that response (p = 0.12). CONCLUSIONS: These data suggest that PBMC mitochondrial bioenergetics in older adults may be partially corrected by 6 weeks of daily 20mg supplementation with MitoQ, but that those changes are not related to changes in microvascular endothelial function. 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.