ArticleNature aging2026
GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging.
Article in Nature aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- Review
- The immunology behind inflammaging-causes, sources, and mechanisms.The Journal of allergy and clinical immunology · 2026Review
- The ageing immune system as a driver of systemic ageing.Nature reviews. Immunology · 2026Review
- Inflammatory Memory of Adipose Tissue Macrophages: From CD68 Footprint to Cardiometabolic and Cancer Risk During Weight Cycling.International journal of molecular sciences · 2026Review
- Siah2 regulates lipid uptake in adipose tissue macrophages.The Journal of biological chemistry · 2026Article
- Masticatory myalgia to headache-like secondary hypersensitivity induces gene plasticity at dura mater.The journal of headache and pain · 2026Article
- Article
- The Sixth Annual Symposium of the Midwest Aging Consortium.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- The regulatory mechanism of NLRP3 inflammasome in the "immune paralytic-overactivation" imbalance in sepsis: the latest progress from molecular signaling to clinical translation.Frontiers in immunology · 2026Review
- Immune signaling as a determinant of cellular identity and tissue function.Frontiers in immunology · 2026Review
Corrections and comments
- Update of
Authors and funding
12 authors.
Funding
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 chromatin with sequencing analyses suggest that GDF3 induces a shift toward an inflammatory state by limiting methylation-dependent chromatin compaction. Leveraging human adipose tissue samples and 11,084 participants from the atherosclerosis risk in communities study, we validate the relevance of GDF3 to aging in humans. These findings position the GDF3-SMAD2/3 axis as a critical driver of age-associated chromatin remodeling and a promising therapeutic target for mitigating macrophage-related inflammation in aging.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.