Peripheral blood mononuclear cell mitochondrial bioenergetics are related to vascular endothelial function in young and older adults.

Mitochondrial oxygen consumption rate (JO2) in PBMCs was lower in older adults at higher energetic states but not at baseline or lower energetic states.

• JO2 was similar between groups at baseline (P = 0.08) and lower energetic states (PCr2, PCr3; P ≥ 0.09)
• At PCr1, JO2 was 14.05 ± 2.11 vs. 12.03 ± 2.98 pmol·s⁻¹·10⁶ cells⁻¹ in young vs. older adults (P = 0.03)
• At PGMS (pyruvate, glutamate, malate, and succinate), JO2 was 20.61 ± 2.11 vs. 16.58 ± 3.56 pmol·s⁻¹·10⁶ cells⁻¹ in young vs. older adults (P = 0.0009)
• Young adults: n = 18, mean age 21 ± 2 yr; older adults: n = 17, mean age 66 ± 4 yr

Mitochondrial membrane potential (Δψm) was hypopolarized in older adults compared with young adults across all energetic states.

• Δψm was hypopolarized in older compared with young adults at all energetic states (P ≤ 0.003)
• Membrane potential was measured using fluorometry in PBMCs in response to substrate provision and bioenergetic creatine kinase clamp at physiological ATP:ADP ratios
• Energetic states tested included PCr1, PCr2, PCr3, and PGMS conditions

Antioxidant buffering capacity (AoxBC) was lower in older adults compared with young adults, despite no significant differences in H2O2 emission or production.

• AoxBC was 52.59 ± 15.44% in older adults vs. 63.49 ± 10.30% in young adults (P = 0.03)
• AoxBC was calculated as the percentage of H2O2 produced but not emitted
• There were no statistical differences in H2O2 emission (P = 0.43) or H2O2 production (P = 0.18) between groups
• H2O2 production was quantified using inhibitors of glutathione reductase and thioredoxin/peroxiredoxin

Age-related changes in PBMC mitochondrial JO2 and Δψm were associated with flow-mediated dilation (FMD), a measure of endothelial function.

• JO2 at PGMS was related to FMD (P = 0.02)
• Δψm was related to FMD at PGMS (P = 0.0008), PCr2 (P = 0.04), and PCr3 (P = 0.02)
• Endothelial function was assessed through brachial-artery flow-mediated dilation (FMD)

The study used high-resolution respirometry combined with a bioenergetic creatine kinase clamp to assess PBMC mitochondrial function at physiological ATP:ADP ratios.

• High-resolution respirometry and fluorometry were used to measure mitochondrial respiration rate (JO2) and membrane potential (Δψm), respectively
• A bioenergetic creatine kinase (CK) clamp was applied at physiological ATP:ADP ratios corresponding to PCr1, PCr2, and PCr3 states
• Substrates used included pyruvate, glutamate, malate, and succinate (PGMS)
• MtROS emission was measured as hydrogen peroxide (H2O2) emission