Exercise training increases hippocampal plasticity in aging through several possible mechanisms, including increased neurotrophic factors such as BDNF (one of the important mediators of crosstalk between contracted skeletal muscles and the brain during exercise training, crucial for neurogenesis and synaptic plasticity) [30], enhanced synaptic plasticity (through activation the cAMP/PKA/CREB signaling pathway) [39], reduced hippocampal atrophy [40], and decreased inflammation and oxidative stress [41]. The gene discussed is CREB1; the disease is hippocampal atrophy.