Background/Objectives: Physical activity is one of the most powerful lifestyle factors influencing brain health, with growing evidence supporting its role in promoting neuroplasticity, cognitive function, and resilience to age-related neurological decline. Recent studies indicate that these effects are mediated by coordinated molecular responses involving epigenetics, activity-dependent gene expression, metabolic adaptation, and inter-organ communication pathways. This narrative review synthesizes current knowledge from experimental and clinical studies on the neurogenomic and epigenetic mechanisms underlying exercise-induced brain plasticity. Methods: Literature searches were conducted in PubMed, Scopus, Web of Science, and Google Scholar to identify studies examining neurogenomic and epigenetic mechanisms underlying neuroplasticity and cognitive adaptations in response to exercise, with an emphasis on mechanistic and translational evidence. Results: Available evidence, derived predominantly from animal studies and supported by more limited, often indirect human data, indicates that physical activity induces epigenetic modifications, including changes in DNA methylation, histone modifications, and microRNA expression, which contribute to lasting changes in exercise-responsive genes involved in brain plasticity. These adaptations include the upregulation of key neuroplasticity-related mediators that support neurogenesis, synaptic plasticity, angiogenesis, and metabolic adaptation, alongside the downregulation of pathways linked to neuroinflammation, oxidative stress, and apoptotic signalling. Conclusions: Integrating neurogenomics with systems biology approaches offers promising opportunities to better understand how physical activity influences brain plasticity throughout life. These insights may support the development of personalized exercise medicine to improve cognitive health and reduce the risk of neurodegenerative disorders.
Agata Leońska-Duniec (Fri,) studied this question.