Nature Cell Biology, Published online: 26 May 2026; doi:10.1038/s41556-026-01960-6 Wei et al. show that Meg3+ haematopoietic stem cells (HSCs) expand upon ageing and present with an increase in H3K23ac levels observed already at middle age. Inhibiting H3K23ac ameliorates megakaryocyte/platelet and myeloid skewing in aged HSCs.