Exercise intensity shapes acute and prolonged immune and extracellular vesicle responses in older adults

Regular physical activity is a cornerstone of healthy aging, offering a wide range of benefits, including the modulation of immune regulation and reduction of chronic inflammation. With aging closely linked to persistent, low-grade inflammation, i.e. inflammaging, the effects of exercise intensity on acute immune responses in older adults remain not fully understood. In this study, we explored how moderate and intense acute continuous exercise impact immune cell activation, cytokine production and large extracellular vesicle (lEV) release in healthy elderly individuals. Fourteen participants completed a moderate continuous exercise intervention (60% VO2max for 30 minutes), while nineteen engaged in an intense continuous exercise session until exhaustion. Blood samples were collected at baseline, and at 1- and 24-hours post-exercise. Immune cell characterization by flow cytometry revealed distinct changes in monocyte subsets and NK cells activation across both exercise intensities. Intense exercise was associated with elevated proinflammatory TNF levels, accumulation of circulating plasma-derived lEV and changes in their surface marker expression after 24 hours. Additionally, we identified sex-specific differences, including distinct activation profiles in innate immunity, alterations in EV release from CD4+ and HLA+ cells, and an exercise-induced increase in IL-6 observed exclusively in females. These findings suggest that moderate continuous acute exercise enhances immune cell activation without altering cell counts, while intense continuous exercise triggers acute proinflammatory immune response. Further research should clarify the long-term implications and fundamental mechanisms of exercise-induced immune modulation in aging populations. Key points summaryO_LIDiminished immune function upon aging is increasing disease risk. This study examines how tailored acute exercise interventions stimulate immune regulation in older adults addressing age-related inflammatory challenges. C_LIO_LIAcute continuous moderate and intense exercise elicit distinct immune responses in elderly individuals with marked differences between sexes. Interestingly, IL-6 levels increased 30 min moderate exercise exclusively in females. C_LIO_LIExercise promotes the release of extracellular vesicles (EVs) and modulates peripheral immunity, suggesting a potent mechanism by which physical activity supports immune resilience in aging. C_LIO_LITailored acute exercise regimens for older adults may enhance immune health, mitigating age-related inflammatory risks and enhancing resilience. C_LIO_LIThis study emphasizes the need for further research on exercise-driven modulation focusing on sex differences and their implications for targeted interventions upon aging. C_LI