ArticleScientific reports2019
Mitochondrial Dysfunction in Aged Macrophages and Lung during Primary Streptococcus pneumoniae Infection is Improved with Pirfenidone.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 41 citations in OpenAlex.
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- GRSF1 loss in THP-1 macrophages promotes senescence-associated transcription in neighboring fibroblasts.Scientific reports · 2025Article
- The Dual Role of Cellular Senescence in Macrophages: Unveiling the Hidden Driver of Age-Related Inflammation in Kidney Disease.International journal of biological sciences · 2025Review
- Drugs targeting TGF-β/Notch interaction attenuate hypertrophic scar formation by optic atrophy 1-mediated mitochondrial fusion.Molecular and cellular biochemistry · 2024Article
- Pirfenidone alleviates smoke inhalation lung injury of rats via the NF-κB signaling pathway.Immunity, inflammation and disease · 2024Article
- Unveiling mechanisms of lung aging in COPD: A promising target for therapeutics development.Chinese medical journal pulmonary and critical care medicine · 2024Review
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- Macrophage senescence in health and diseases.Acta pharmaceutica Sinica. B · 2024Review
- Heightened cholesterol 25-hydroxylase expression in aged lung duringFrontiers in aging · 2024Article
- Mitochondrial dysfunction at the cornerstone of inflammatory exacerbation in aged macrophages.Exploration of immunology · 2023Article
- Review
- Female reproductive life span is extended by targeted removal of fibrotic collagen from the mouse ovary.Science advances · 2022Article
- Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci.Cells · 2022Article
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- RIPK3 Activates MLKL-mediated Necroptosis and Inflammasome Signaling duringAmerican journal of respiratory cell and molecular biology · 2021Article
- Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells.Nature microbiology · 2021Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Pneumococcal infections remain a leading cause of death in older adults, with the most serious cases occurring in persons ≥65 years of age. There is an urgent need to investigate molecular pathways underlying these impairments and devise new therapeutics to modulate innate immunity. The goal of our current study is to understand the impact of chronological aging on mitochondrial function in response to Streptococcus pneumoniae, a causative agent of bacterial pneumonia. Using chronologically aged murine models, our findings demonstrate that decreased ATP production is associated with dysregulated mitochondrial complex expression, enhanced oxidative stress, diminished antioxidant responses, and decreased numbers of healthy mitochondria in aged adult macrophages and lung in response to S. pneumoniae. Pre-treatment of aged macrophages with pirfenidone, an anti-fibrotic drug with antioxidant and anti-inflammatory properties, improved mitochondrial function and decreased cellular oxidative stress responses. In vivo administration of pirfenidone decreased superoxide formation, increased healthy mitochondria number, improved ATP production, and decreased inflammatory cell recruitment and pulmonary oedema in aged mouse lung during infection. Taken together, our data shed light on the susceptibility of older persons to S. pneumoniae and provide a possible therapeutic to improve mitochondrial responses in this population.
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