Polyunsaturated fatty acids and antioxidants are important mediators in the central nervous system. Lipid derivatives may control the production of proinflammatory agents and regulate NF-κB activity, microglial activation, and fatty acid oxidation; on the other hand, antioxidants, such as glutathione and ascorbate, have been shown to signal through transmitter receptors and protect against acute and chronic oxidative stress, modulating the activity of different signaling pathways. Several authors have investigated the role of these nutrients in the brains of the young and the aged in degenerative diseases such as Alzheimer's and Parkinson's, and during brain aging due to adiposity- and physical inactivity-mediated metabolic disturbances, chronic inflammation, and oxidative stress. Through a literature review, we aimed to highlight recent data on the role of adiposity, fatty acids, antioxidants, and physical inactivity in the pathophysiology of the brain and in the molecular mechanisms of senescence. Data indicate the complexity and necessity of endogenous/dietary antioxidants for the maintenance of redox status and the control of neuroglial signaling under stress. Recent studies also indicate that omega-3 and -6 fatty acids act in a competitive manner to generate mediators for energy metabolism, influencing feeding behavior, neural plasticity, and memory during aging. Finding pharmacological or dietary resources that mitigate or prevent neurodegenerative affections continues to be a great challenge and requires additional effort from researchers, clinicians, and nutritionists in the field.
Keywords: aging; ascorbic acid; docosahexaenoic acid; essential fatty acids; glutathione; growth factors; inflammation; nervous system; neuroprotection; senescence.