Platelet Mitochondrial Function, Physical Performance, and Body Composition in Older People Living with HIV: A Preliminary Study.

Mitochondrial dysfunction(definition) is a hallmark of aging and age-related physical decline in people living with HIV (PLWH) who experience accelerated aging. This pilot study investigated the relationships between platelet mitochondrial function, physical performance, and body composition in older, sedentary PLWH compared with older, sedentary HIV-negative controls. Platelets have the potential to act as minimally invasive and easily accessible biomarkers for systemic mitochondrial bioenergetics and may serve as a practical biomarker in aging-related research. We analyzed correlations between mitochondrial parameters, protein levels, and measures of physical performance and body composition in a cohort of predominantly African American men (<i>n</i> = 7 PLWH, <i>n</i> = 7 controls). Body composition was assessed using dual-energy X-ray absorptiometry (DXA), and exercise capacity through VO₂ peak and strength tests. Platelet mitochondrial bioenergetic parameters were measured by oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Key mitochondrial proteins SIRT3, COXII, DRP1, and OPA1 were evaluated by Western blotting. The PLWH and HIV-negative control groups were similar in age and cardiorespiratory fitness. In PLWH, basal OCR and ATP-linked respiration showed strong positive correlations with VO₂ peak (r = 0.874, <i>p</i> < 0.05 and r = 0.862, <i>p</i> < 0.05, respectively) and negative correlations with BMI (r = -0.856, <i>p</i> < 0.05 and r = -0.849, <i>p</i> < 0.05, respectively). SIRT3 emerged as a potential key player, demonstrating strong positive correlations with basal OCR (r = 0.804, <i>p</i> < 0.05), ATP-linked respiration (r = 0.787, <i>p</i> < 0.05), and VO₂ peak (r = 0.970, <i>p</i> < 0.001), and negative correlations with BMI (r = -0.830, <i>p</i> < 0.05) and fat mass (r = -0.827, <i>p</i> < 0.05) in PLWH. Analyses focused on within-group associations in PLWH because bioenergetic measures were obtained using different Seahorse platforms in PLWH and controls, precluding valid direct quantitative comparisons between groups. Our findings provide evidence for significant associations between platelet mitochondrial bioenergetics, specific mitochondrial proteins (particularly SIRT3), and key physical attributes in older, sedentary PLWH. These preliminary findings suggest that platelets may serve as minimally invasive biomarkers of systemic mitochondrial health, contribute to our understanding of mitochondrial function in HIV-associated accelerated aging, and inform future interventions to enhance mitochondrial function and improve health outcomes in this vulnerable population. However, results should be interpreted cautiously given the small sample size and exploratory design and should be considered hypothesis-generating rather than definitive. Larger, demographically more diverse studies that include HIV-negative controls are needed to validate these associations and determine their clinical relevance.