Youth-associated platelet-derived chemokine reverses brain aging through neuroimmune mechanisms

Abstract

Age-related loss of brain function has been seen as inevitable, yet recent work leveraging the systemic environment challenges this notion. Schroer et al. demonstrate that youth-associated platelet factor 4 (PF4) partially restores brain function in aged mice while reducing peripheral immune dysfunction, supporting periphery-based approaches to treat age-associated brain disorders.

Keywords: aging; hippocampus; platelets; rejuvenation; young blood.

Figure 1.. Systemic PF4 treatment in aged mice mitigates peripheral and hippocampal inflammation to improve cognitive function.

Systemic treatment of aged mice with PF4 results in changes in innate and adaptive immune function in the periphery, including reduced levels of myeloid/neutrophil inflammatory signals and reduced age-related exhaustion and cytotoxic T cell markers with concomitant improvements in hippocampus-dependent learning and memory, synapse function, and microglial activation. Mice lacking CXCR3 exhibit a partial loss of PF4-mediated CNS benefits, raising the possibility that CXCR3-expressing T cells are critical for the effects of PF4. Changes in the CNS following PF4 treatment may be mediated by shifts in peripheral cytokines, immune cell infiltration, or direct action of PF4, though future studies will clarify the relative contributions of these mechanisms and PF4’s regulation of neuroimmune interactions in the CNS. Abbreviations: CXCR3, C-X-C Motif Chemokine Receptor 3; CNS, central nervous system; PF4, platelet factor 4. This figure was created with tools from BioRender.com.