ArticleBlood2019
TNF-α-driven inflammation and mitochondrial dysfunction define the platelet hyperreactivity of aging.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
194 citing papers in PubMed, 3 syntheses or guidelines pooled it, 305 citations in OpenAlex.
- Associations of novel complete blood count-derived inflammatory markers with psoriasis: a systematic review and meta-analysis.Archives of dermatological research · 2024Pooled it
- Platelet abnormalities in autoimmune thyroid diseases: A systematic review and meta-analysis.Frontiers in immunology · 2022Pooled it
- Research Priorities for Plasma and Platelet Transfusion Strategies in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2022Pooled it
- Impact of Sugammadex versus Neostigmine on Diaphragmatic Function and Respiratory Recovery in Morbidly Obese Patients with Moderate Neuromuscular Block: A Randomised Double-Blind Controlled Trial.Drug design, development and therapy · 2026Trial
- Myokines and mitochondrial function in cardiometabolic diseases.Journal of physiology and biochemistry · 2026Review
- Platelet Cyclophilin D Drives Cholesterol Crystal Embolism-Related Acute Kidney Injury and Kidney Infarction.Journal of the American Society of Nephrology : JASN · 2026Article
- Insights Into the Role of Platelet Factor 4 in Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2026Review
- Review
- Platelet subpopulations and contribution to hemostasis.Blood science (Baltimore, Md.) · 2026Review
- Mitochondrial DNA leakage in oocytes activates cGAS-STING signaling to drive ovarian aging.Nature aging · 2026Article
- Platelet-derived mitochondrial transfer in cancer metastasis: mechanisms, functional consequences, and translational opportunities.Clinical & experimental metastasis · 2026Review
- Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Immune Dysregulation in Branched Chain Organic Acidemias.Journal of inherited metabolic disease · 2026Review
- Andes virus and the aging host: lessons from the 2026 outbreak and a framework for age-related disease severity.GeroScience · 2026Review
- Platelet hyperactivation drives oxidized mitochondrial DNA-induced neutrophil extracellular traps formation in biliary atresia.JHEP reports : innovation in hepatology · 2026Article
- Article
- StackAge: an ensemble-based clock for precise quantification of biological age using multi-omics data.Briefings in bioinformatics · 2026Article
- Hematopoietic Aging and Leukemia: Mechanistic and Therapeutic Insights.International journal of molecular sciences · 2026Review
- Research progress on blood therapy for anti-aging.Journal of advanced research · 2026Review
- Ophiopogon japonicus-derived plant exosomes: a promising strategy for blocking the progression of diabetic vasculopathy to myocardial infarction.BMC complementary medicine and therapies · 2026Article
134 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
25 authors at 8 institutions in 3 countries.
Funding
Abstract
Aging and chronic inflammation are independent risk factors for the development of atherothrombosis and cardiovascular disease. We hypothesized that aging-associated inflammation promotes the development of platelet hyperreactivity and increases thrombotic risk during aging. Functional platelet studies in aged-frail adults and old mice demonstrated that their platelets are hyperreactive and form larger thrombi. We identified tumor necrosis factor α (TNF-α) as the key aging-associated proinflammatory cytokine responsible for platelet hyperreactivity. We further showed that platelet hyperreactivity is neutralized by abrogating signaling through TNF-α receptors in vivo in a mouse model of aging. Analysis of the bone marrow compartments showed significant platelet-biased hematopoiesis in old mice reflected by increased megakaryocyte-committed progenitor cells, megakaryocyte ploidy status, and thrombocytosis. Single-cell RNA-sequencing analysis of native mouse megakaryocytes showed significant reprogramming of inflammatory, metabolic, and mitochondrial gene pathways in old mice that appeared to play a significant role in determining platelet hyperreactivity. Platelets from old mice (where TNF-α was endogenously increased) and from young mice exposed to exogenous TNF-α exhibited significant mitochondrial changes characterized by elevated mitochondrial mass and increased oxygen consumption during activation. These mitochondrial changes were mitigated upon TNF-α blockade. Similar increases in platelet mitochondrial mass were seen in platelets from patients with myeloproliferative neoplasms, where TNF-α levels are also increased. Furthermore, metabolomics studies of platelets from young and old mice demonstrated age-dependent metabolic profiles that may differentially poise platelets for activation. Altogether, we present previously unrecognized evidence that TNF-α critically regulates megakaryocytes resident in the bone marrow niche and aging-associated platelet hyperreactivity and thrombosis.
Indexed as
Identifiers
What OpenQuestion holds
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.