PBMCs Mitochondrial Respiration and Its Relation to Immunity, Fitness, and Metabolic Risk in the Healthy Elderly

Mitochondrial function plays a central role in regulating immunological and metabolic processes, particularly during successful aging. This cross-sectional study aimed to investigate associations between mitochondrial respiration of peripheral blood mononuclear cells (PBMCs; MR_PBMC) and key markers of immune function, systemic inflammation, and metabolic health in a cohort of healthy older adults. Sixteen healthy, physically active participants aged > 55 years (male: n = 9; female: n = 7; age: 64 ± 3.7 years; BMI: 24.3 ± 2.9; VO_2peak: 31.1 ± 8.8 mL/min/kg) were recruited. Participants were tested for their maximal oxygen uptake (VO_2peak) as well as cardiovascular and metabolic risk factors. Venous fasting blood samples were collected. For further analysis, MR_PBMC was measured using the Oroboros O2k-Oxygraph. T cell subsets were analyzed by flow cytometry, serum cytokines by LUMINEX assays, and gene expression by qPCR analysis. We found positive associations between basal and maximal MR_PBMC, and the percentage of CD4⁺ T cells, with a notable link to naïve CD4⁺ T cells (p < 0.05). Maximal MR_PBMC was negatively associated with proportion of effector memory CD4⁺ T cells (p < 0.05). Basal MR_PBMC showed negative associations with pro-inflammatory serum cytokine tumor necrosis factor alpha (TNF-α), while maximal MR_PBMC was positively associated with interleukin 8 (IL-8), intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor (VEGF) (p < 0.05). Intracellular signaling markers, including mRNA level of signal transducer and activator of transcription 3 (STAT3), also showed positive associations with maximal MR_PBMC (p < 0.05). No correlations were found for variables such as cardiorespiratory fitness, IL-6, and IL-10. In conclusion, PBMC mitochondrial bioenergetics are linked to T cell subpopulations and systemic inflammation in healthy older adults. Higher mitochondrial respiration reflecting better mitochondrial function favors a more naïve CD4⁺ T cell distribution. In contrast, lower mitochondrial function was observed in individuals with a more pro-inflammatory profile, suggesting a potential relationship between immune status and mitochondrial bioenergetics in older adults.