ArticleScience advances2021
Elevated type I interferon responses potentiate metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Age difference of patients with and without invasive aspergillosis: a systematic review and meta-analysis.BMC infectious diseases · 2024Pooled it
- Mechanistic reprogramming of the mtDNA-cGAS-STING axis in cellular senescence: from mitochondrial homeostatic disruption to inflammatory and immune outcomes.Biogerontology · 2026Review
- From mitochondria to innate immunity: The mtDNA-driven cGAS/STING-NLRP3 cascade and its therapeutic implications in neurodegenerative diseases (Review).Experimental and therapeutic medicine · 2026Review
- Cardiomyocyte-intrinsic somatic mtDNA mutations induce an OXPHOS-dependent immune response and promote progressive heart failure.Science advances · 2026Article
- Mitochondrial RNA-Type I Interferon Axis in Sjögren's Disease: Molecular Mechanisms and Translational Implications.International journal of molecular sciences · 2026Review
- NAMPT activation uncovers a senescence-specific vulnerability and promotes healthy aging in combination with NAM.bioRxiv : the preprint server for biology · 2026Article
- Metformin alleviates side effects and supports the resumption of interferon therapy in polycythemia vera and essential thrombocythemia.Haematologica · 2026Article
- Persistence of large mtDNA rearrangements linked to premature aging in Pol γ exonuclease-deficient mice.Nucleic acids research · 2026Article
- LPAR4 mediates resistance to interferon-induced stress in soft tissue sarcoma.Science advances · 2026Article
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- Comparative analysis of muscle pathologies and metabolic signaling in mouse models of mitochondrial dysfunction.Scientific reports · 2026Article
- Alterations in mitochondria and cellular senescence in aged sEH null female kidneys.GeroScience · 2026Article
- Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.Cellular and molecular neurobiology · 2026Article
- Follicular Helper T Cells and B Cell Maturation in Patients with 22q11.2 Deletion Syndrome and Recurrent Infections.Journal of clinical immunology · 2026Article
- Dose-dependent activation of the Hippo pathway by Type I and Type III interferons suppresses tissue repair by human bronchial epithelial cells.PLoS biology · 2026Article
- Article
- Ubiquitous Expression ofLife (Basel, Switzerland) · 2025Article
- IFN It Isn't Broke, It May Still Be Driving Disease: IFNs as Mediators of Senescence in Chronic Obstructive Pulmonary Disease.American journal of respiratory cell and molecular biology · 2025Article
- Sterile inflammation in laminopathies.European journal of cell biology · 2025Review
- IFN-Mediated Bronchial Epithelium Cellular Senescence in Chronic Obstructive Pulmonary Disease.American journal of respiratory cell and molecular biology · 2025Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial dysfunction is a key driver of inflammatory responses in human disease. However, it remains unclear whether alterations in mitochondria-innate immune cross-talk contribute to the pathobiology of mitochondrial disorders and aging. Using the polymerase gamma (POLG) mutator model of mitochondrial DNA instability, we report that aberrant activation of the type I interferon (IFN-I) innate immune axis potentiates immunometabolic dysfunction, reduces health span, and accelerates aging in mutator mice. Mechanistically, elevated IFN-I signaling suppresses activation of nuclear factor erythroid 2-related factor 2 (NRF2), which increases oxidative stress, enhances proinflammatory cytokine responses, and accelerates metabolic dysfunction. Ablation of IFN-I signaling attenuates hyperinflammatory phenotypes by restoring NRF2 activity and reducing aerobic glycolysis, which combine to lessen cardiovascular and myeloid dysfunction in aged mutator mice. These findings further advance our knowledge of how mitochondrial dysfunction shapes innate immune responses and provide a framework for understanding mitochondria-driven immunopathology in POLG-related disorders and aging.
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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.