Neurobiological Synergy of Plant and Animal Sources of Omega-3 and Exercise in Aging: Implications for Molecular Signaling, Memory, Spatial Learning, and Brain Function

Aging is associated with cognitive decline, impaired spatial learning, and diminished brain function, significantly impacting quality of life (QoL). Emerging evidence suggests that lifestyle interventions, like omega-3 fatty acids (FAs) intake and regular exercise, can mitigate these age-related deficits by targeting key molecular pathways implicated in oxidative damage, inflammation, and reduced fibrinolytic activity. By doing so, omega-3 FAs, principally eicosapentaenoic acid and docosahexaenoic acid, influence signaling pathways that enhance synaptic plasticity, prevent apoptosis, and promote neurogenesis. Similarly, moderate exercise stimulates neurogenesis, synaptic plasticity, and mitochondrial biogenesis. The synergistic effects of omega-3 and exercise may further amplify neuroprotective mechanisms by enhancing hippocampal function, improving cerebral blood flow, and modulating gut-brain axis interactions. This review explores the molecular crosstalk between exercise and omega-3 FAs, highlighting their joint impact on spatial learning, memory retention, and brain health in aging. Additionally, we discuss potential translational implications for neurodegenerative disease prevention and cognitive longevity. An understanding of these molecular mechanisms could pave the way for individualized interventions to optimize brain function, thus improving quality of life in aging subjects.