Benefits of exercise training on cerebrovascular and cognitive function in ageing

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  Figure 1.. Ageing is associated with hormonal imbalances and increased low-grade systemic inflammation. It is also associated with the increased production of reactive oxygen species (ROS), which may be due to diminished nuclear regulation factor 2 and superoxide dismutase expression and increased expression of nicotinamide adenine dinucleotide phosphate oxidase complexes, resulting in increased mitochondrial superoxide production.120 Uncoupled endothelial nitric oxide (NO) synthase (eNOS) increases superoxide production by catalysing nicotinamide adenine dinucleotide phosphate, instead of synthesising NO. Increased arginase activity reduces l-arginine supply, thus promoting the uncoupling of eNOS.69,70 This may also be associated with diminished tetrahydrobiopterin availability and increased asymmetrical dimethylarginine concentrations, which subsequently acts as a competitive inhibitor of eNOS, thus reducing NO biosynthesis.71 These promote and lead to endothelial dysfunction, which subsequently manifests as local ischemia and micro-haemorrhages in the microvasculature, leading to reductions in capillary density and BBB function (i.e. reduced cerebrovascular function).121,122 It may also…

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  Figure 2.. A summary of the potential mechanisms that may be elicited by exercise in improving cerebrovascular function and cognition. CBF: cerebral blood flow; eNOS: endothelial nitric oxide synthase, NO: nitric oxide; BHB: beta-hydroxybutyrate; GH: growth hormone; VEGF: vascular endothelial growth factor; BDNF: brain-derived neurotrophic factor; IGF1: insulin-like growth factor-1; PGC-1a: peroxisome proliferator-activated receptor gamma coactivator 1-alpha.