Research Article

Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain

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Science  10 Jul 2020:
Vol. 369, Issue 6500, pp. 167-173
DOI: 10.1126/science.aaw2622

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Plasma transfers exercise benefit in mice

Exercise has a broad range of beneficial healthful effects. Horowitz et al. tested whether the beneficial effects of exercise on neurogenesis in the brain and improved cognition in aged mice could be transferred in plasma (blood without its cellular components) from one mouse to another (see the Perspective by Ansere and Freeman). Indeed, aged mice that received plasma from young or old mice that had exercised showed beneficial effects in their brains without hitting the treadmill. The authors identified glycosylphosphatidylinositol-specific phospholipase D1 as a factor in plasma that might, in part, mediate this favorable effect.

Science, this issue p. 167; see also p. 144

Abstract

Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)–specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.

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