Neuron-glia (mis)interactions in brain energy metabolism during aging

Life expectancy in humans is increasing, resulting in a growing aging population, that is accompanied by an increased disposition to develop cognitive deterioration. Hypometabolism is one of the multiple factors related to inefficient brain function during aging. This review emphasizes the metabolic interactions between glial cells (astrocytes, oligodendrocytes, and microglia) and neurons, particularly, during aging. Glial cells provide support and protection to neurons allowing adequate synaptic activity. We address metabolic coupling from the expression of transporters, availability of substrates, metabolic pathways, and mitochondrial activity. In aging, the main metabolic exchange machinery is altered with inefficient levels of nutrients and detrimental mitochondrial activity that results in high reactive oxygen species levels and reduced ATP production, generating a highly inflammatory environment that favors deregulated cell death. Here, we provide an overview of the glial-to-neuron mechanisms, from the molecular components to the cell types, emphasizing aging as the crucial risk factor for developing neurodegenerative/neuroinflammatory diseases.