ArticleAging cell2018
Loss of sirtuin 1 and mitofusin 2 contributes to enhanced ischemia/reperfusion injury in aged livers.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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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.
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Who cites it
49 citing papers in PubMed, 71 citations in OpenAlex.
- Article
- Mitophagy in Hepatic Ischemia-Reperfusion Injury: From Mitochondrial Dysfunction to Therapeutic Targeting.Biomolecules · 2026Review
- Article
- Article
- Involvement of SIRT1-mediated aging in liver diseases.Frontiers in cell and developmental biology · 2025Review
- Integrated approach to reducing polypharmacy in older people: exploring the role of oxidative stress and antioxidant potential therapy.Redox report : communications in free radical research · 2024Review
- FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC.Nature communications · 2024Article
- Sirtuins in kidney health and disease.Nature reviews. Nephrology · 2024Review
- Quercetin ameliorates ferroptosis of rat cardiomyocytes via activation of the SIRT1/p53/SLC7A11 signaling pathway to alleviate sepsis‑induced cardiomyopathy.International journal of molecular medicine · 2023Article
- Autophagy and Senescence: The Molecular Mechanisms and Implications in Liver Diseases.International journal of molecular sciences · 2023Review
- Review
- Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury.Biomedicines · 2023Review
- Acteoside ameliorates hepatic ischemia-reperfusion injuryInternational journal of biological sciences · 2023Article
- Identify Key Genes Correlated to Ischemia-Reperfusion Injury in Aging Livers.Disease markers · 2023Article
- Increased oxidative stress caused by impaired mitophagy aggravated liver ischemia and reperfusion injury in diabetic mice.Journal of diabetes investigation · 2023Article
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Mitochondrial Autophagy in Ischemic Aged Livers.Cells · 2022Review
- miR‑141 impairs mitochondrial function in cardiomyocytes subjected to hypoxia/reoxygenation by targeting Sirt1 and MFN2.Experimental and therapeutic medicine · 2022Article
- Preserving and rejuvenating old organs for transplantation: novel treatments including the potential of senolytics.Current opinion in organ transplantation · 2022Review
- Circadian Control of Transcriptional and Metabolic Rhythms in Primary Hepatocytes.Methods in molecular biology (Clifton, N.J.) · 2022Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Ischemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age-mediated hypersensitivity to I/R injury remain poorly understood. Here, we investigated how sirtuin 1 (SIRT1) and mitofusin 2 (MFN2) are affected by I/R in aged livers. Young (3 months) and old (23-26 months) male C57/BL6 mice were subjected to hepatic I/R in vivo. Primary hepatocytes isolated from each age group were also exposed to simulated in vitro I/R. Biochemical, genetic, and imaging analyses were performed to assess cell death, autophagy flux, mitophagy, and mitochondrial function. Compared to young mice, old livers showed accelerated liver injury following mild I/R. Reperfusion of old hepatocytes also showed necrosis, accompanied with defective autophagy, onset of the mitochondrial permeability transition, and mitochondrial dysfunction. Biochemical analysis indicated a near-complete loss of both SIRT1 and MFN2 after I/R in old hepatocytes, which did not occur in young cells. Overexpression of either SIRT1 or MFN2 alone in old hepatocytes failed to mitigate I/R injury, while co-overexpression of both proteins promoted autophagy and prevented mitochondrial dysfunction and cell death after reperfusion. Genetic approaches with deletion and point mutants revealed that SIRT1 deacetylated K655 and K662 residues in the C-terminus of MFN2, leading to autophagy activation. The SIRT1-MFN2 axis is pivotal during I/R recovery and may be a novel therapeutic target to reduce I/R injury in aged livers.
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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.