Exercise conditioned plasma dampens inflammation via clusterin and boosts memory

Physical exercise seems universally beneficial to human and animal health, slowing cognitive aging and neurodegeneration. Cognitive benefits are tied to increased plasticity and reduced inflammation within the hippocampus, yet little is known about the factors and mechanisms mediating these effects. We discovered \"runner\" plasma, collected from voluntarily running mice, infused into sedentary mice recapitulates the cellular and functional benefits of exercise on the brain. Importantly, runner plasma reduces baseline neuroinflammatory gene expression and prominently suppresses experimentally induced brain inflammation. Plasma proteomic analysis shows a striking increase in complement cascade inhibitors including clusterin, which is necessary for the anti-inflammatory effects of runner plasma. Cognitively impaired patients participating in structured exercise for 6 months showed higher plasma clusterin levels, which correlated positively with improvements in endurance and aerobic capacity. These findings demonstrate the existence of anti-inflammatory \"exercise factors\" that are transferrable, benefit the brain, and are present in humans engaging in exercise.