Young blood-derived platelet factors abate inflammation and rescue recognition in aging.

We show that platelet factors transfer rejuvenating effects of young plasma to the aging brain. Proteomic analysis of plasma from young and aged mice identified age-related changes in platelets. Systemic exposure of aged animals to the platelet fraction of young plasma decreased hippocampal neuroinflammation at a transcriptional and cellular level and ameliorated cognitive impairments. We identified the platelet-derived chemokine CXCL4/Platelet Factor-4 (PF4) as a pro-youthful circulating factor. Systemic PF4 administration decreased age-related neuroinflammation, restored the aging peripheral immune system to a more youthful state, and improved hippocampal-dependent learning and memory in aged mice. Examination of hippocampi from aged mice treated with young plasma, young plasma-derived platelets or saline control (samples 8-24). Examination of hippocampal microglia isolated from aged mice treated with platelet factor 4 (PF4) or saline vehicle control (samples 1-7).