Age-related declines in energy metabolism, muscle strength, and physical performance have been linked to lower mitochondrial respiratory capacity. This study examines the association between mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and metabolic flexibility, muscle strength, and physical function in healthy older adults.
What this study does not show
This study does not establish a causal relationship between mitochondrial respiration and improved physical performance outcomes, nor does it provide evidence for interventions to enhance mitochondrial function.
Evidence scorecard
- Analytic validity: established
- Clinical validity: partial
- Clinical utility: not established
The evidence is based on primary research involving human subjects.
The study involved fifty community-dwelling older adults (22 men, 28 women; average age 70 years). The researchers quantified PBMC mitochondrial respiratory capacity using high-resolution respirometry, assessing ROUTINE, LEAK, and MAX states. They also measured postprandial substrate oxidation during steady-state treadmill walking at 60% of VO2max using indirect calorimetry, calculating fat and carbohydrate oxidation rates with standard stoichiometric equations.
Metabolic flexibility was defined as a lower respiratory exchange ratio (RER) and higher relative fat oxidation at a fixed workload. Muscle strength was evaluated through handgrip dynamometry and one-repetition maximum leg extension tests, while physical function was assessed by gait speed and five-repetition chair rise time.
Linear and logistic regression analyses, adjusted for age, sex, skeletal muscle index, physical activity, and high-sensitive C-reactive protein concentrations, were used to test associations. Exploratory K-means clustering was employed to identify mitochondrial respiration phenotypes.
Results indicated that higher ROUTINE respiration correlated with lower RER (rho = -0.335, p = 0.020), greater fat utilization (rho = -0.334, p = 0.019), increased grip strength (rho = 0.302, p = 0.033), and faster gait speed (rho = 0.324, p = 0.022). Adjusted regression analyses confirmed that ROUTINE respiration was associated with greater fat oxidation (β = 0.212, 95% CI 0.049; 0.375), lower RER (β = -0.160, 95% CI -0.300; -0.020), and higher gait speed (β = 0.153, 95% CI 0.028; 0.277). Similar associations were observed for ATP-linked respiration.
Cluster analysis revealed high- and low-respiration phenotypes. The low-respiration group exhibited lower counter-movement jump (CMJ) height (OR: 0.204, 95% CI 0.055; 0.763) and quadriceps strength (OR: 0.373, 95% CI 0.155; 0.897) compared to the high-respiration group.
In conclusion, higher PBMC ROUTINE respiration in healthy older adults was associated with a more fat-dominant substrate utilization profile during submaximal exercise, greater muscle strength, and faster gait speed. This suggests that PBMC respiratory capacity may reflect systemic bioenergetic status relevant to exercise substrate utilization and physical performance in aging.