PHYSICAL EXERCISE, BDNF, AND COGNITIVE AGING: MECHANISMS, EVIDENCE, AND CLINICAL IMPLICATIONS

Aim: To review the biological mechanisms, clinical evi­dence, and translational implications of exercise-induced BDNF modulation in the context of cognitive aging, and to examine the role of physical activity as a modifiable lifestyle factor supporting brain health.

Methods: A narrative review of current scientific litera­ture was conducted, including experimental and clinical studies, randomized controlled trials, meta-analyses, and dose–response analyses. Evidence was selected based on relevance to physical activity, BDNF signaling, and cognitive outcomes across the lifespan.

Results: BDNF plays a critical role in neurogenesis, synaptic plasticity, and neuronal survival, particularly within the hippocampus, through complex signaling pat­hways involving pro-BDNF and mature BDNF isoforms. Physical exercise enhances BDNF expression via neuro­nal activity-dependent mechanisms and increased cere­bral blood flow, involving calcium signaling, CREB acti­vation, and hemodynamic responses. Both aerobic and resistance exercise increase BDNF levels and improve cognitive function, with a nonlinear dose–response re­lationship emerging from recent evidence. Exercise inter­ventions have shown beneficial effects across aging, de­pression, and early neurodegenerative disease. However, the literature is limited by methodological heterogeneity, small sample sizes, and a lack of standardized protocols.

Conclusions: Physical activity represents a promising non-pharmacological strategy for promoting cognitive health and reducing the risk of neurodegenerative di­sorders. Future research should focus on personalized exercise prescriptions, improved methodological rigor, and a deeper understanding of the mechanisms linking exercise, BDNF, and cognition across the lifespan.