ArticleAging cell2023
Age-dependent loss of hepatic SIRT1 enhances NLRP3 inflammasome signaling and impairs capacity for liver fibrosis resolution.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Prognostic value of FIB-4 and NFS for cardiovascular events in patients with and without NAFLD.BMC public health · 2025Pooled it
- Article
- What Explains the Pattern of Fibrosis in Chronic Graft-Versus-Host Disease?Clinical transplantation · 2026Review
- The Role of SIRT1 in Mediating Bone Marrow Edema and Its Interface With Bone Remodeling.Immunity, inflammation and disease · 2026Review
- Review
- A preliminary study on NLRP3 activation and the interventional effects of MCC950 in Con A-induced EAH mice.Translational pediatrics · 2026Article
- Sirtuin 1 as an emerging exerkine in the aging process: unveiling its multifaceted biological roles.Biogerontology · 2026Review
- Marine Bioactives in Liver Aging: Mechanistic Insights and Translational Potential.Marine drugs · 2026Review
- Protective effect of melatonin against age-related ischemia-reperfusion injury is associated with the NLRP3 inflammasome pathway.Journal of physiology and biochemistry · 2026Article
- Spatial niche remodeling of senescent liver-resident immune cells and its role in chronic liver diseases.Frontiers in medicine · 2026Review
- Periodontitis and MASLD: a narrative review of the direct oral-hepatic pathway.Frontiers in cellular and infection microbiology · 2026Review
- Aging-driven metabolic abnormalities remodel intercellular communication through the gut-liver-heart axis and may promote coronary artery disease: the key role of bile acid metabolism.Frontiers in immunology · 2026Review
- Cerium oxide nanoparticles attenuate hepatic failure via blocking TGF-β/Smads and upregulating Nrf2/HO-1 signaling pathways in liver fibrosis rat model.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Aging Promotes Spontaneous Liver Injury: Insights from Metabolic, Inflammatory, and Fibrotic Pathways in C57BL/6 Mice.Biomolecules · 2025Article
- The impact of aging on liver health and the development of liver diseases.Hepatology communications · 2025Review
- Aging-Associated Liver Sinusoidal Endothelial Cells Dysfunction Aggravates the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.Aging cell · 2025Article
- Involvement of SIRT1-mediated aging in liver diseases.Frontiers in cell and developmental biology · 2025Review
- The Effects of M2 Macrophages-Derived Exosomes on Urethral Fibrosis and Stricture in Scar Formation.ImmunoTargets and therapy · 2025Article
- Involvement of role of HMGB1-NLRP3 pathway in systemic disorders.Frontiers in cell and developmental biology · 2025Review
- SIRT1 Enhancement is Required for the Induction of Anti-Inflammatory Effect of Micheliolide in Carbon Tetrachloride Induced Liver Fibrosis in Mice.Journal of inflammation research · 2025Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Our studies indicate that the longevity factor SIRT1 is implicated in metabolic disease; however, whether and how hepatocyte-specific SIRT1 signaling is involved in liver fibrosis remains undefined. We characterized a functional link of age-mediated defects in SIRT1 to the NLRP3 inflammasome during age-related liver fibrosis. In multiple experimental murine models of liver fibrosis, we compared the development of liver fibrosis in young and old mice, as well as in liver-specific SIRT1 knockout (SIRT1 LKO) mice and wild-type (WT) mice. Liver injury, fibrosis, and inflammation were assessed histologically and quantified by real-time PCR analysis. In a model of hepatotoxin-induced liver fibrosis, old mice displayed more severe and persistent liver fibrosis than young mice during liver injury and after injury cessation, as characterized by inhibition of SIRT1, induction of NLRP3, infiltration of macrophages and neutrophils, activation of hepatic stellate cells (HSCs), and excessive deposition and remodeling of the extracellular matrix. Mechanistically, deletion of SIRT1 in hepatocytes resulted in NLRP3 and IL-1β induction, pro-inflammatory response, and severe liver fibrosis in young mice, mimicking the ability of aging to impair the resolution of established fibrosis. In an aging mouse model, chronic-plus-binge alcohol feeding-induced liver fibrosis was attenuated by treatment with MCC950, a selective NLRP3 inhibitor. NLRP3 inhibition ameliorated alcoholic liver fibrosis in old mice by repressing inflammation and reducing hepatocyte-derived danger signaling-ASK1 and HMGB1. In conclusion, age-dependent SIRT1 defects lead to NLRP3 activation and inflammation, which in turn impairs the capacity to resolve fibrosis during 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.