ArticleScience translational medicine2014
Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 433 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
433 citing papers in PubMed, 1 synthesis or guideline pooled it, 677 citations in OpenAlex.
- The Role of Herpes Viruses in Pulmonary Fibrosis.Frontiers in medicine · 2021Pooled it
- The Iron Lung: Ferroptosis and Iron Regulation in Aging and Lung Diseases.Physiology (Bethesda, Md.) · 2027Review
- Non-Resolving Repair in Idiopathic Pulmonary Fibrosis: From Failed Cellular Transitions to Architectural Lock-In.International journal of molecular sciences · 2026Review
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- Murine models of pulmonary fibrosis: mechanisms, limitations and translational insights.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Ageing-associated regenerative failure in the lung: stem cell senescence and transitional cell persistence in idiopathic pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Skin on Drugs: Psychotropic Compounds in Cutaneous Biology.International journal of molecular sciences · 2026Review
- Activation of the impaired NAMPT/SIRT7/SOD2 axis restores alveolar progenitor cell renewal in idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2026Article
- Middle-aged mice treated with GHK-Cu peptide administered intraperitoneally or intranasally show behavioral rescue but divergent hippocampal aging programs.Research square · 2026Article
- Review
- The metabolic code of pulmonary disease: from mechanisms to therapeutic opportunities.Breathe (Sheffield, England) · 2026Review
- Quantifying Information Exchange Between Cells in Inflammaging.Bioengineering (Basel, Switzerland) · 2026Article
- Article
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- The impact of garlic and its active metabolites on degenerative musculoskeletal diseases.Frontiers in pharmacology · 2026Review
- Smoking accelerates immunosenescence in multiple sclerosis.Frontiers in immunology · 2026Review
- Cellular senescence in Crohn's disease: a double-edged sword in intestinal fibrosis.Frontiers in immunology · 2026Review
- Emerging concepts and novel mechanisms in organ fibrosis.NPJ Regenerative medicine · 2025Article
- Wnt signaling pathway in lung aging and aging-related chronic lung diseases.Biogerontology · 2025Review
373 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The incidence and prevalence of pathological fibrosis increase with advancing age, although mechanisms for this association are unclear. We assessed the capacity for repair of lung injury in young (2 months) and aged (18 months) mice. Whereas the severity of fibrosis was not different between these groups, aged mice demonstrated an impaired capacity for fibrosis resolution. Persistent fibrosis in lungs of aged mice was characterized by the accumulation of senescent and apoptosis-resistant myofibroblasts. These cellular phenotypes were sustained by alterations in cellular redox homeostasis resulting from elevated expression of the reactive oxygen species-generating enzyme Nox4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-4] and an impaired capacity to induce the Nrf2 (NFE2-related factor 2) antioxidant response. Lung tissues from human subjects with idiopathic pulmonary fibrosis (IPF), a progressive and fatal lung disease, also demonstrated this Nox4-Nrf2 imbalance. Nox4 mediated senescence and apoptosis resistance in IPF fibroblasts. Genetic and pharmacological targeting of Nox4 in aged mice with established fibrosis attenuated the senescent, antiapoptotic myofibroblast phenotype and led to a reversal of persistent fibrosis. These studies suggest that loss of cellular redox homeostasis promotes profibrotic myofibroblast phenotypes that result in persistent fibrosis associated with aging. Our studies suggest that restoration of Nox4-Nrf2 redox balance in myofibroblasts may be a therapeutic strategy in age-associated fibrotic disorders, potentially able to resolve persistent fibrosis or even reverse its progression.
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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.