Astrocytes as Perspective Targets of Exercise- and Caloric Restriction-Mimetics

Enhanced mental and physical activity can have positive effects on the function of aging brain, both in the experimental animals and human patients, although cellular mechanisms underlying these effects are currently unclear. There is a growing evidence that pre-clinical stage of many neurodegenerative diseases involves changes in interactions between astrocytes and neurons. Conversely, astrocytes are strategically positioned to mediate the positive influence of physical activity and diet on neuronal function. Thus, development of therapeutic agents which could improve the astroglia-neuron communications in ageing brain is of crucial importance. Recent advances in studies of cellular mechanisms of brain longevity suggest that astrocyte-neuron communications have a vital role in the beneficial effects of caloric restriction, physical exercise and their pharmacological mimetics on synaptic homeostasis and cognitive function. In particular, our recent data indicate that noradrenaline uptake inhibitor atomoxetine can enhance astrocytic Ca²⁺-signaling and astroglia-driven modulation of synaptic plasticity. Similar effects were exhibited by caloric restriction-mimetics metformin and resveratrol. The emerged data also suggest that astrocytes could be involved in the modulatory action of caloric restriction and its mimetics on neuronal autophagy. Still, the efficiency of astrocyte-targeting compounds in preventing age-related cognitive decline is yet to be fully explored, in particular in the animal models of neurodegenerative diseases and autophagy impairment.