1 Fatty acids , antioxidants and physical activity in 2 brain aging 3

Polyunsaturated fatty acids (PUFAs) and antioxidants are important mediators in the 14 central nervous system (CNS). Lipid derivatives may be used to generate endocannabinoids or 15 prostanoids derived from arachidonic acid, which attenuates excitotoxicity in quadripartite 16 synapses with a focus in astrocytes and microglia; on the other hand, antioxidants, such as 17 glutathione (GSH) and ascorbate, have been shown to signal through transmitter receptors and 18 protect against acute and chronic oxidative stress, modulating the activity of different signaling 19 pathways. Several authors have investigated the role of these nutrients in young and senescent 20 brain, as well as in degenerative conditions such as Alzheimer’s and Parkinson's diseases. Through 21 literature review, we aimed to highlight recent data on the role of fatty acids, antioxidants and 22 physical activity in physiology and in molecular mechanisms of brain senescence. Data indicate the 23 complexity and essentiality of endogenous/dietary antioxidants for maintenance of the redox status 24 and control of neuroglial signaling under stress. Recent studies also indicate that omega-3 and -6 25 fatty acids act in a competitive manner to generate mediators for energy metabolism, feeding 26 behavior, plasticity and memory mechanisms throughout aging. Finding pharmacological or 27 dietary resources that mitigate or prevent neurodegenerative affections continues to be a great 28 challenge and require additional efforts from researchers, clinicians and nutritionists in the field. 29