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Neuroimmunology

A platelet-derived factor protects the ageing brain

Nature Reviews Immunology volume 23, page 614 (2023)Cite this article

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Systemic rejuvenating interventions — such as the transfer of blood plasma from young mice into older animals — can reverse age-related cognitive impairments, but the mechanisms involved are unclear. Now, the Villeda laboratory reports that platelet factor 4 (PF4; also known as CXCL4) is a blood-associated factor that reduces inflammation and cognitive decline in an age-dependent manner.

PF4, which is a chemokine involved in coagulation and other immune processes, has been shown to be elevated in blood serum after rejuvenating interventions and has also been linked to the beneficial effects of exercise on the brain. The authors therefore focused on this platelet-derived factor and found that PF4 levels were elevated in platelet fractions and blood plasma preparations from young mice compared with aged animals. They observed a similar increase in PF4 levels in the blood of young humans compared with healthy older adults. Systemic administration of PF4 to aged mice decreased hippocampal expression of pro-inflammatory genes (including Tnf, Nfkb1 and Il1b) and reduced markers of microglial cell activation, but PF4 did not show this effect when administered to young mice. By contrast, middle-aged PF4-deficient mice showed increased evidence of hippocampal inflammation. RNA-seq of hippocampi from aged mice indicated that PF4 treatment also increased the expression of markers associated with synaptic plasticity. Thus, PF4 seems to have an age-dependent effect on reducing inflammation and enhancing synaptic plasticity in the hippocampus.

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Yvonne Bordon

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  1. Yvonne Bordon
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Correspondence to Yvonne Bordon.

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Bordon, Y. A platelet-derived factor protects the ageing brain. Nat Rev Immunol 23, 614 (2023). https://doi.org/10.1038/s41577-023-00939-w

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