ArticleNature aging2025
Gut microbial-derived phenylacetylglutamine accelerates host cellular senescence.
Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis 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
48 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Global research trends in gut microbiota and cellular senescence: a bibliometric and visual analysis from 2015 to 2025.Frontiers in microbiology · 2025Pooled it
- Cardiovascular-kidney-metabolic syndrome through the lens of gut‑derived uremic toxins.Gut microbes · 2026Review
- Gut microbiota metabolic reprogramming drives the development of metabolic diseases in the host.Gut microbes · 2026Review
- Senolytics dasatinib and quercetin in metabolic dysfunction-associated steatohepatitis: a proof-of-principle randomized, controlled trial.Nature metabolism · 2026Article
- Metabolic Profiling of Epigenetic Aging and Its Associations With Aging-Related Phenotypes and Modifiable Lifestyle Factors.Aging cell · 2026Article
- A Mechanism-Based Framework for Anti-Aging Strategies: From Metabolic Regulation to Senotherapy and Stem Cell-Based Interventions.Aging cell · 2026Review
- Metabolomic signatures for diagnosis and clinical severity in Parkinson's disease.EBioMedicine · 2026Article
- Research progress of traditional Chinese medicine interventions for aging-related nervous system diseases.Biogerontology · 2026Review
- Phenylacetic Acid, a Gut Microbially Produced Metabolite, Reduces Atherosclerosis Burden and Impacts Host Lipid Homeostasis.Journal of the American Heart Association · 2026Article
- GATA4-Driven Transcription of HtrA1 Promotes Cellular Senescence in Ménière's Disease and Age-Related Audio-Vestibular Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Longitudinal metabolomics profiles reveal increased gut microbial protein fermentation during Spaceflight.Nature communications · 2026Article
- Integration of bulk and single-cell RNA-seq data identifies a cellular senescence-related prognostic signature in liver hepatocellular carcinoma.Discover oncology · 2026Article
- Article
- The gut microbiome and ageing trajectories: mechanisms and clinical implications.Nature reviews. Endocrinology · 2026Review
- Immunosenescence and Vaccine Efficacy in Aging: Dynamic Interplay of Gut Microbiota and mTOR Signaling Pathways.Aging cell · 2026Review
- A BBB-permeable βScience advances · 2026Article
- Environmental Enrofloxacin Exposure as a Modifiable Driver of Mitochondria-Mediated Intestinal Aging and Barrier Dysfunction.Aging cell · 2026Article
- Serum Metabolomics Study Reveals a Diagnostic Model for Lung Cancer Brain Metastasis.The clinical respiratory journal · 2026Article
- An orally administrable hydrogen-bonded organic framework (HOF)-based nanoreactor to reprogram metabolism for senescence intervention.National science review · 2026Article
- Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming.npj aging · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gut microbiota plays a crucial role in the host health in the aging process. However, the mechanisms for how gut microbiota triggers cellular senescence and the consequent impact on human aging remain enigmatic. Here we show that phenylacetylglutamine (PAGln), a metabolite linked to gut microbiota, drives host cellular senescence. Our findings indicate that the gut microbiota alters with age, which leads to increased production of phenylacetic acid (PAA) and its downstream metabolite PAGln in older individuals. The PAGln-induced senescent phenotype was verified in both cellular models and mouse models. Further experiments revealed that PAGln induces mitochondrial dysfunction and DNA damage via adrenoreceptor (ADR)-AMP-activated protein kinase (AMPK) signaling. Blockade of ADRs as well as senolytics therapy impede PAGln-induced cellular senescence in vivo, implying potential anti-aging therapies. This combined evidence reveals that PAGln, a naturally occurring metabolite of human gut microbiota, mechanistically accelerates host cellular senescence.
Indexed as
Identifiers
39794469What 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.