Identifying therapeutics to delay, and potentially reverse, age-related cognitive decline is critical in light of the increased incidence of dementia-related disorders forecasted in the growing older population¹. Here we show that platelet factors transfer the benefits of young blood to the ageing brain. Systemic exposure of aged male mice to a fraction of blood plasma from young mice containing platelets decreased neuroinflammation in the hippocampus at the transcriptional and cellular level and ameliorated hippocampal-dependent cognitive impairments. Circulating levels of the platelet-derived chemokine platelet factor 4 (PF4) (also known as CXCL4) were elevated in blood plasma preparations of young mice and humans relative to older individuals. Systemic administration of exogenous PF4 attenuated age-related hippocampal neuroinflammation, elicited synaptic-plasticity-related molecular changes and improved cognition in aged mice. We implicate decreased levels of circulating pro-ageing immune factors and restoration of the ageing peripheral immune system in the beneficial effects of systemic PF4 on the aged brain. Mechanistically, we identified CXCR3 as a chemokine receptor that, in part, mediates the cellular, molecular and cognitive benefits of systemic PF4 on the aged brain. Together, our data identify platelet-derived factors as potential therapeutic targets to abate inflammation and rescue cognition in old age.

鉴于预计老年人口数量不断增加，痴呆相关疾病的发病率将会增加，因此确定延缓并可能逆转与年龄相关的认知能力下降的治疗方法至关重要¹。在这里，我们证明血小板因子将年轻血液的益处转移到衰老的大脑。将老年雄性小鼠全身暴露于含有血小板的年轻小鼠血浆中，可在转录和细胞水平上减少海马体的神经炎症，并改善海马体依赖性认知障碍。与年长个体相比，年轻小鼠和人类血浆制剂中血小板衍生趋化因子血小板因子 4 (PF4)（也称为 CXCL4）的循环水平升高。全身给予外源性 PF4 可减轻与年龄相关的海马神经炎症，引起突触可塑性相关的分子变化，并改善老年小鼠的认知能力。我们认为循环促衰老免疫因子水平的降低和衰老外周免疫系统的恢复与全身性 PF4 对衰老大脑的有益作用有关。从机制上讲，我们确定 CXCR3 是一种趋化因子受体，它在一定程度上介导系统性 PF4 对衰老大脑的细胞、分子和认知益处。总之，我们的数据确定血小板衍生因子是减轻炎症和挽救老年认知的潜在治疗靶点。