GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging.

ABSTRACT: Aging is characterized by amplified inflammation, including proinflammatory macrophages and increased susceptibility to endotoxemia. Here we uncover a mechanism by which macrophages maintain their inflammatory phenotype through autocrine GDF3-SMAD2/3 signaling, which ultimately exacerbates endotoxemia. We show that inflammatory adipose tissue macrophages display an age-dependent increase in GDF3, a TGFβ-family cytokine. Lifelong systemic or myeloid-specific Gdf3 deletion leads to reduced endotoxic inflammation. Using pharmacological interventions to modulate the GDF3-SMAD2/3 axis, we demonstrate its role in regulating the inflammatory adipose tissue macrophage phenotype and endotoxemia lethality in old mice. Mechanistically, single-cell RNA sequencing and assay for transposase-accessible c

SUBMITTER: Jang IH 

PROVIDER: S-EPMC12823384 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature