ArticleCell death discovery2021
Autophagy deficiency promotes M1 macrophage polarization to exacerbate acute liver injury via ATG5 repression during aging.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Markers of the ageing macrophage: a systematic review and meta-analysis.Frontiers in immunology · 2023Pooled it
- Timing-dependent anti-inflammatory effects of empagliflozin in monocyte-derived macrophages from post-myocardial infarct patients with type 2 diabetes.Cardiovascular diabetology · 2026Trial
- SIRT6-Mediated Deacetylation of ATF3 Promotes Silica-Induced Lung Fibrosis by Enhancing its Nuclear Import via Binding to Importin α.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Autophagy functions in lung macrophages and dendritic cells to regulate allergen-dependent inflammatory responses.Autophagy · 2026Article
- Natural Alkaloids Against Liver Injury: Mechanistic Insights and Multi-Target Therapeutic Potential.Biomolecules · 2026Review
- Macrophage autophagy-dependent M2 polarization mediates the protective effect of ADSC-conditioned medium against acute lung injury.Stem cell research & therapy · 2026Article
- Investigation of molecular immune regulation mechanisms and therapeutic target prediction in pancreatic cancer based on bioinformatics and genetics.Clinics (Sao Paulo, Brazil) · 2026Article
- Dual control of liver regeneration by Nr1d1 homeostasis and Klf2 checkpoint.Cell death discovery · 2026Article
- Telomerase Knockout in Myeloid Cells Predisposes Mice to Foam Cell Formation, Dyslipidemia, Lung Fibrosis, and Cardiac Dysfunction.Aging cell · 2026Article
- Radiation-induced autophagy regulates fibroblast mitochondrial metabolism and crosstalk with triple-negative breast cancer cells.Cell reports · 2026Article
- Article
- HIV associated immune aging among people living with HIV: implications for long-term antiretroviral therapy and potential HIV cure interventions in sub-Saharan Africa.Frontiers in immunology · 2026Review
- Oral microbiome-SASP-aging axis: mechanisms and targeted intervention strategies for age-related diseases.Journal of oral microbiology · 2026Review
- Understanding Liver and Digestive Diseases: A Paved Road to Improve Diagnosis, Management, and Treatment.Exploration of digestive diseases · 2026Article
- Senescence of bone marrow mesenchymal stromal cells: a narrative review of mechanisms, functional consequences, and rejuvenation strategies for age-related disorders.Stem cell research & therapy · 2025Review
- HIV infection and immunosenescence: challenges and intervention strategies.BMC medicine · 2025Review
- Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.Translational neurodegeneration · 2025Review
- Macrophages and autophagy: partners in crime.The FEBS journal · 2025Review
- Exploring ferroptosis and miRNAs: implications for cancer modulation and therapy.Molecular and cellular biochemistry · 2025Review
- Aging immunity: unraveling the complex nexus of diet, gut microbiome, and immune function.Immunometabolism (Cobham, Surrey) · 2025Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Aging disrupts the maintenance of liver homeostasis, which impairs hepatocyte regeneration and aggravates acute liver injury (ALI), ultimately leading to the development of acute liver failure (ALF), a systemic inflammatory response, and even death. Macrophages influence the progression and outcome of ALI through the innate immune system. However, it is still unclear how macrophages regulate ALI during aging. The variation in macrophage autophagy with aging and the influence on macrophage polarization and cytokine release were assessed in BMDMs in vitro. Then, after BMDMs subjected to several treatments were intravenously or intraperitoneally injected into mice, thioacetamide (TAA)-induced ALI (TAA-ALI) was established, and its effects on inflammation, injury, and mortality were assessed. We found that aging aggravated the liver injury, along with increases in the levels of proinflammatory mediators, presenting a senescence-associated secretory phenotype (SASP), which promoted macrophage polarization to the M1 phenotype. In addition, autophagy levels decreased significantly in aged mice, which was ascribed to ATG5 repression during aging. Notably, enhancing autophagy levels in aged BMDMs restored macrophage polarization to that observed under young conditions. Finally, autophagy restoration in aged BMDMs enhanced the protective effect against TAA-ALI, similar to M2 macrophages induced by IL-4. Overall, we demonstrated that the influence of aging on macrophage polarization is an important aggravating factor in TAA-ALI, and the autophagy in macrophages is associated with the aging phenotype.
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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.