Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice

Exercise has positive effects on the brain during aging. Here the authors show that in mice, platelet-released exerkine PF4 mediates the effects of exercise on the brain. The beneficial effects of physical activity on brain ageing are well recognised, with exerkines, factors that are secreted into the circulation in response to exercise, emerging as likely mediators of this response. However, the source and identity of these exerkines remain unclear. Here we provide evidence that an anti-geronic exerkine is secreted by platelets. We show that platelets are activated by exercise and are required for the exercise-induced increase in hippocampal precursor cell proliferation in aged mice. We also demonstrate that increasing the systemic levels of the platelet-derived exerkine CXCL4/platelet factor 4 (PF4) ameliorates age-related regenerative and cognitive impairments in a hippocampal neurogenesis-dependent manner. Together these findings highlight the role of platelets in mediating the rejuvenating effects of exercise during physiological brain ageing.

Automated summary

Exercise has positive effects on the aging brain, and platelet-released exerkines, such as PF4, mediate these effects. Platelets are activated by exercise and are necessary for exercise-induced increase in precursor cell proliferation in the hippocampus of aged mice. Increasing the levels of the platelet-derived exerkine PF4 improves age-related cognitive impairments through hippocampal neurogenesis. These findings emphasize the role of platelets in the rejuvenating effects of exercise during brain aging.