Junyu Bai, Jinqiao Zhang
Global population aging faces immunosenescence, increasing infection risk, reducing vaccine efficacy, and raising chronic disease burden, a major public health challenge. Identifying safe, effective interventions is paramount. This review evaluates the potential of regular exercise as a non-pharmacological strategy to counteract key features of immunosenescence. Exercise acutely redistributes immune cells and, via long-term adaptation, triggers coordinated effects including neuroendocrine modulation, myokine release, metabolic remodeling, and gut microbiota improvement. These adaptations appear to reduce chronic inflammation, may help optimize adaptive immune cell repertoires, and are associated with enhanced immune surveillance. Exercise type, intensity, and duration uniquely influence immunomodulatory outcomes, underscoring the need for personalized prescriptions. Current research supports the immunoprotective benefits of exercise; however, gaps remain regarding the functional significance of exercise-induced biomarker changes, the differential activation of mechanistic pathways across exercise modalities, and the translation of short-term biomarker improvements into reduced infection risk or enhanced vaccine responses in older adults. Future studies must address these issues to advance evidence-based, precise exercise recommendations for healthy aging.