Distinct roles for NF-κB in hematopoietic stem cells and the bone marrow milieu in promoting hematopoietic aging.

ABSTRACT: Hematopoietic aging is characterized by chronic inflammation associated with myeloid bias, hematopoietic stem cell (HSC) accumulation, and functional HSC impairment. Yet it remains unclear how inflammation promotes aging phenotypes. Nuclear factor κB (NF-κB) both responds to and directs inflammation, and we present an experimental model of elevated NF-κB activity ("inhibitor of κB deficient" [IκB^-]) to dissect its role in hematopoietic aging phenotypes. We find that while elevated NF-κB activity is not sufficient for HSC accumulation, HSC-autonomous NF-κB activity impairs their functionality, leading to reduced bone marrow reconstitution. In contrast, myeloid bias is driven by the IκB^- proinflammatory bone marrow milieu, as observed functionally, epigenomically, and t

SUBMITTER: Chia JJ 

PROVIDER: S-EPMC12515102 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature