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

Odette Leiter, David Brici, Stephen J. Fletcher, Xuan Ling Hilary Yong, Jocelyn Widagdo, Nicholas Matigian, Adam B. Schroer, Gregor Bieri, Daniel G. Blackmore, Perry F. Bartlett, Victor Anggono, Saul A. Villeda and Tara L. Walker ()
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Odette Leiter: The University of Queensland
David Brici: The University of Queensland
Stephen J. Fletcher: The University of Queensland
Xuan Ling Hilary Yong: The University of Queensland
Jocelyn Widagdo: The University of Queensland
Nicholas Matigian: The University of Queensland
Adam B. Schroer: University of California San Francisco
Gregor Bieri: University of California San Francisco
Daniel G. Blackmore: The University of Queensland
Perry F. Bartlett: The University of Queensland
Victor Anggono: The University of Queensland
Saul A. Villeda: University of California San Francisco
Tara L. Walker: The University of Queensland

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-39873-9

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