In young mice, megakaryocytes produce PF4, which in turn drives the maintenance of lineage-balanced, potent HSCs. During aging, the megakaryocytic niche is altered. Megakaryocytes undergo changes in morphology, changes in number, and produce significantly less PF4. This reduction in PF4 contributes to myeloid-biased hematopoiesis and a loss of functionally potent HSCs. Both human and mouse HSC function can be partially restored through direct administration/treatment of recombinant PF4 protein.