ArticleAging cell2021
Necroptosis contributes to chronic inflammation and fibrosis in aging liver.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 170 citations in OpenAlex.
- A nomogram based on psoas muscle index predicting long-term cirrhosis incidence in non-cirrhotic patients with HBV-related acute‑on‑chronic liver failure.Scientific reports · 2023Trial
- Programmed cell death in inflammation: interactions and holistic perspective.Cellular & molecular immunology · 2026Review
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- The immunology behind inflammaging-causes, sources, and mechanisms.The Journal of allergy and clinical immunology · 2026Review
- GDF15 in Liver Fibrosis: Molecular Mechanisms, Immunoregulatory Functions, and Therapeutic Potential.Biomolecules · 2026Review
- Kidney‑enriched lipid nanoparticles delivering ANXA2 alleviate renal ischemia-reperfusion injury via CHMP2A-mediated necroptosis inhibition.Journal of nanobiotechnology · 2026Article
- A Non-Canonical Role for Hepatocyte MLKL in Promoting Mitochondrial Dysfunction and Senescence in the Aging Liver.Aging cell · 2026Article
- Ginsenoside Rb1 mitigates senescence-associated hepatic steatosis in mice through enhanced lysine degradation.Journal of ginseng research · 2026Article
- Resveratrol alleviates intervertebral disc degeneration by regulating ferroptosis of nucleus pulposus cells.NPJ systems biology and applications · 2026Article
- Review
- Therapeutic potential of glycyrrhizic acid in inflammation-related diseases: from HMGB1-oriented molecular insights to preclinical application.Archives of pharmacal research · 2026Review
- Machine learning-based multi-omic analysis identifies CEP55, DLGAP5, and EZH2 as regulated cell death biomarkers linked to immunotherapy resistance in hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- Article
- Aging disrupts hepatocyte zonation homeostasis in mice and humans.Hepatology (Baltimore, Md.) · 2026Article
- Transcriptomic and multi-layer variant analysis identifies STAT3 and HIF1A as central regulators of regulated cell death pathways in lung squamous cell carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The Role of Neutrophil, Monocyte and Macrophage Calprotectin and S100A12 in the Fibrotic Process.Biomolecules · 2026Review
- Necroptosis induced by MLKL overexpression in liver triggers cellular senescence and leads to chronic inflammation and fibrosis.GeroScience · 2026Article
- New Vistas for Withania somnifera in Signal Transduction of Inflammation and Aging.Pharmaceutical research · 2026Review
- Bacillus cereus Induces Necroptosis in Microglia via the RIPK1/3-MLKL Pathway.MicrobiologyOpen · 2026Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Inflammaging, characterized by an increase in low-grade chronic inflammation with age, is a hallmark of aging and is strongly associated with various age-related diseases, including chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Because necroptosis is a cell death pathway that induces inflammation through the release of DAMPs, we tested the hypothesis that age-associated increase in necroptosis contributes to chronic inflammation in aging liver. Phosphorylation of MLKL and MLKL oligomers, markers of necroptosis, as well as phosphorylation of RIPK3 and RIPK1 were significantly upregulated in the livers of old mice relative to young mice and this increase occurred in the later half of life (i.e., after 18 months of age). Markers of M1 macrophages, expression of pro-inflammatory cytokines (TNFα, IL6 and IL1β), and markers of fibrosis were all significantly upregulated in the liver with age and the change in necroptosis paralleled the changes in inflammation and fibrosis. Hepatocytes and liver macrophages isolated from old mice showed elevated levels of necroptosis markers as well as increased expression of pro-inflammatory cytokines relative to young mice. Short-term treatment with the necroptosis inhibitor, necrostatin-1s (Nec-1s), reduced necroptosis, markers of M1 macrophages, fibrosis, and cell senescence as well as reducing the expression of pro-inflammatory cytokines in the livers of old mice. Thus, our data show for the first time that liver aging is associated with increased necroptosis and necroptosis contributes to chronic inflammation in the liver, which in turn appears to contribute to liver fibrosis and possibly CLD.
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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.