ArticleJournal of hepatology2017
Aging aggravates alcoholic liver injury and fibrosis in mice by downregulating sirtuin 1 expression.
Article in Journal of hepatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 192 citations in OpenAlex.
- Role of HMGB1 in Neuroinflammation.Molecular neurobiology · 2026Review
- Targeted clearance of senescent cells alleviates alcohol-associated liver disease by restoring cellular function and immune balance.GeroScience · 2026Article
- Gut Microbiota and Ageing: A Critical Crosstalk in Alcohol-Related Liver Disease.Microorganisms · 2026Review
- Resolvin D1 alleviates liver inflammation and fibrosis through SIRT1-mediated NF-κB and TGF-β1/Smads pathways.Journal of inflammation (London, England) · 2026Article
- Interferon Regulatory Factors in Alcohol-Associated Liver Disease: Cell-Type Programs, Danger Signaling, and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- The role of lysine acylation in metabolic dysregulation and inflammatory responses within the hepatic immune microenvironment of MASLD.Frontiers in immunology · 2026Review
- Integrative and interpretable machine learning framework for early non-invasive detection of clinically significant liver fibrosis.Frontiers in medicine · 2026Article
- Aging Promotes Spontaneous Liver Injury: Insights from Metabolic, Inflammatory, and Fibrotic Pathways in C57BL/6 Mice.Biomolecules · 2025Article
- Interplay between aging and metabolic diseases: from molecular mechanisms to therapeutic horizons.Medical review (2021) · 2025Review
- The impact of aging on liver health and the development of liver diseases.Hepatology communications · 2025Review
- The Protective Effects of Quercetin on Ferritinophagy in Alcoholic-Induced Liver Iron Overload.Current medical science · 2025Article
- Navigating liver cancer with mouse models: a comprehensive overview of HCC experimental systems.Journal of liver cancer · 2025Article
- Pharmacokinetics and Biodistribution of Polymeric Nanoparticles Loaded with a Small Molecule Drug in Mice with Alcoholic Liver Disease.Molecular pharmaceutics · 2025Article
- Aging-Associated Liver Sinusoidal Endothelial Cells Dysfunction Aggravates the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.Aging cell · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Therapeutic potential of nicotinamide and ABT263 in alcohol-associated liver disease through targeting cellular senescence.MedComm · 2025Article
- Ethyl Lactate Ameliorates Hepatic Steatosis and Acute-on-Chronic Liver Injury in Alcohol-Associated Liver Disease by Inducing Fibroblast Growth Factor 21.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Involvement of SIRT1-mediated aging in liver diseases.Frontiers in cell and developmental biology · 2025Review
- Loss ofJHEP reports : innovation in hepatology · 2025Article
- Gut microbiota and HMGB1/NLRP3/GSDMD inflammasome-dependent pyroptosis: mechanisms by physcion ameliorates alcoholic liver fibrosis.Frontiers in pharmacology · 2025Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsAging is known to exacerbate the progression of alcoholic liver disease (ALD), but the underlying mechanisms remain obscure. The aim of this study was to use a chronic plus binge ethanol feeding model in mice to evaluate the effects of aging on alcohol-induced liver injury.
methodsC57BL/6 mice were subjected to short-term (10days) ethanol plus one binge or long-term (8weeks) ethanol plus multiple binges of ethanol. Liver injury and fibrosis were determined. Hepatic stellate cells (HSCs) were isolated and used in in vitro studies.
resultsMiddle-aged (12-14months) and old-aged (>16months) mice were more susceptible to liver injury, inflammation, and oxidative stress induced by short-term plus one binge or long-term plus multiple binges of ethanol feeding when compared to young (8-12weeks) mice. Long-term plus multiple binges of ethanol feeding induced greater liver fibrosis in middle-aged mice than that in young mice. Hepatic expression of sirtuin 1 (SIRT1) protein was downregulated in the middle-aged mice compared to young mice. Restoration of SIRT1 expression via the administration of adenovirus-SIRT1 vector ameliorated short-term plus binge ethanol-induced liver injury and fibrosis in middle-aged mice. HSCs isolated from middle-aged mice expressed lower levels of SIRT1 protein and were more susceptible to spontaneous activation in in vitro culture than those from young mice. Overexpression of SIRT1 reduced activation of HSCs from middle-aged mice in vitro with downregulation of PDGFR-α and c-Myc, while deletion of SIRT1 activated HSCs isolated from young mice in vitro. Finally, HSC-specific SIRT1 knockout mice were more susceptible to long-term chronic-plus-multiple binges of ethanol-induced liver fibrosis with upregulation of PDGFR-α expression.
conclusionsAging exacerbates ALD in mice through the downregulation of SIRT1 in hepatocytes and HSCs. Activation of SIRT1 may serve as a novel target for the treatment of ALD. LAY SUMMARY: Aged mice are more susceptible to alcohol-induced liver injury and fibrosis, which is, at least in part, due to lower levels of sirtuin 1 protein in hepatocytes and hepatic stellate cells. Our findings suggest that sirtuin 1 activators may have beneficial effects for the treatment of alcoholic liver disease in aged patients.
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