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Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity. While, the molecular mechanisms behind this phenomenon are not fully understood. In this study, we observed that the expression of FUS is increased in aged HSCs and enforced FUS recapitulates the phenotype of aged HSCs through RGG-mediated aberrant FUS phase transition. By utilizing Fus-gfpmice, we observed that FUShighHSCs exhibit compromised FUS mobility and resemble aged HSCs both functionally and transcriptionally. The percentage of FUShighHSCs is increased upon physiological aging and replication stress, and FUSlowHSCs of aged mice exhibit youthful function. Mechanistically, FUShighHSCs exhibit a different global chromatin organization compared to FUSlowHSCs, which is observed in aged HSCs. A large number of TADs are merged in aged HSCs due to the compromised binding of CTCF with chromatin, which is invoked by aberrant FUS condensates. It is notable that the transcriptional alteration between FUShighand FUSlowHSCs originates from the merged TADs and are enriched in HSC aging-related genes. Collectively, this study for the first time reveals that aberrant FUS mobility promotes HSC aging by altering chromatin structure.