ArticleNature communications2025
Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed.
- A YAP-TEAD-CTCF Transcriptional Regulatory Axis Associated With the Elimination of Injured Hepatocytes From the Liver.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Article
- Review
- Senolytics dasatinib and quercetin in metabolic dysfunction-associated steatohepatitis: a proof-of-principle randomized, controlled trial.Nature metabolism · 2026Article
- Hepatocyte Growth Hormone Receptor Ablation Is Associated With Aging Phenotypes and Hepatic Mitochondrial Dysfunction.Aging cell · 2026Article
- Senescent Human Liver Endothelial Cells Mediate CD4Immunology · 2026Article
- Hepatocyte hedgehog signaling controls ferroptosis to alleviate aging-related organ dysfunction.JCI insight · 2026Article
- From linear methylation to spatial metabolic control: Rethinking DNMT1 targeting in MASLD: Letter to the editor on "DNMT1 facilitates the progression of MASLD by impeding transcription mediated by HNF4α and PPARα".Clinical and molecular hepatology · 2026Article
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- Article
- Article
- THEMIS attenuates MASH by suppressing disease-associated hepatocyte induction and hepatocyte senescence in mice.The Journal of clinical investigation · 2026Article
- Redefining senescence through hepatocyte fate changes in liver diseases.Trends in endocrinology and metabolism: TEM · 2026Review
- Causal Effects of a Hepatic Senescence Gene Set on MASLD Fibrosis: A Mendelian Randomization Study and Quercetin Molecular Docking Analysis.Biomedicines · 2026Article
- The natural flavonoid dihydromyricetin targets senescent cells via PRDX2 and alleviates age-related diseases.Nature communications · 2026Article
- p16Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Research advances and application prospects of CAR-T therapy in the treatment of age-related diseases.Frontiers in immunology · 2026Review
- Key Experimental Therapeutics and Knowledge Gaps in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Drug design, development and therapy · 2026Review
- Ubc9-Mediated SUMOylation of RPL3, an Unappreciated Mechanism against Hepatocyte Senescence by Repressing the DHX9-p16 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular senescence in liver diseases: From molecular drivers to therapeutic targeting.Journal of hepatology · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors.
Funding
Abstract
Senescent hepatocytes accumulate in metabolic dysfunction-associated steatotic liver disease (MASLD) and are linked to worse clinical outcomes. However, their heterogeneity and lack of specific markers have made them difficult to target therapeutically. Here, we define a senescent hepatocyte gene signature (SHGS) using in vitro and in vivo models and show that it tracks with MASLD progression/regression across mouse models and large human cohorts. Single-nucleus RNA-sequencing and functional studies reveal that SHGS+ hepatocytes originate from p21+ cells, lose key liver functions and release factors that drive disease progression. One such factor, GDF15, increases in circulation alongside SHGS+ burden and disease progression. Through chemical screening, we identify senolytics that selectively eliminate SHGS+ hepatocytes and improve MASLD in male mice. Notably, SHGS enrichment also correlates with dysfunction in other organs. These findings establish SHGS+ hepatocytes as key drivers of MASLD and highlight a potential therapeutic strategy for targeting senescent cells in liver disease and beyond.
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