Plasma Extracellular Vesicle Signatures of Metabolic Health and Exercise Response in a Pilot Study of Older Adults.

Extracellular vesicles (EVs) are key mediators of intercellular communication and regulators of cellular function, yet their roles in metabolic health and exercise response are poorly understood. This pilot study analyzed plasma from older adults (n=20) in subgroups of the well-characterized STRRIDE study to evaluate plasma EV biomarkers as minimally invasive biomarkers of metabolic health and exercise responsiveness. Plasma EVs comprised highly heterogeneous subpopulations defined by diverse surface markers reflecting complex cellular origins. At baseline, multiple EV biomarkers related to immune cells, skeletal muscle, and mesenchymal stem cells were associated with better indices of insulin action, including nine EV subpopulations with lower fasting insulin concentration and eight with lower Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Low-amount (~1300 kcal/week), vigorous-intensity (65-80% peak VO₂) aerobic exercise increased the FABP4⁺ EV subpopulation in older adults (n=12). High-amount (~2200 kcal/week), vigorous-intensity exercise increased fifteen EV subpopulations in older adults (n=8). These subpopulations arise from a variety of cell sources, including immune cells (primarily lymphoid cells), skeletal and cardiac muscle, erythroid cells, mesenchymal and hematopoietic stem cells. Notably, eight out of fifteen high-amount exercise-induced EV subpopulations were insulin action-related (CD29⁺, CD8⁺, CD56⁺, CD19⁺, MCAD⁺, CD73⁺, CD105⁺ CD235a⁺). The EV-based profiling platform established here is ready for validation in larger human exercise cohorts, including the full STRRIDE cohort.

Duke Scholars

Author William Erle Kraus Medicine, Cardiology

Author Xin Zhang Orthopaedic Surgery