RT Journal Article SR Electronic T1 Exercise conditioned plasma dampens inflammation via clusterin and boosts memory JF bioRxiv FD Cold Spring Harbor Laboratory SP 775288 DO 10.1101/775288 A1 Zurine De Miguel A1 Michael J. Betley A1 Drew Willoughby A1 Benoit Lehallier A1 Niclas Olsson A1 Liana Bonanno A1 Kaci J. Fairchild A1 Kévin Contrepois A1 Joshua E. Elias A1 Thomas A. Rando A1 Tony Wyss-Coray YR 2019 UL http://biorxiv.org/content/early/2019/09/19/775288.abstract AB 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.