{
  "abstract": "The urinary bladder urothelium is crucial for maintaining barrier and signaling functions of the urinary bladder. The urothelium is a metabolically demanding tissue and therefore is particularly susceptible to the impact of aging. Age-associated alterations include increased oxidative stress (e.g., increased ROS) and impaired mitochondrial function that collectively contribute to a high prevalence of bladder dysfunction in older individuals. Emerging evidence suggests that changes in levels/activity of the enzyme purine nucleoside phosphorylase (PNPase) contribute to the extent of oxidative injury, cellular damage and other biological hallmarks of aging. PNPase converts ‘tissue-protective’ purines- that reduce ROS- to ‘tissue-damaging’ purines- that increase ROS. The aim of this study was designed to elucidate whether the endogenous PNPase inhibitor, 8-aminoguanine (8-AG), mitigates bladder nerve damage and age-associated adverse cellular and molecular changes (lipid peroxidation, mitochondrial dysfunction, cellular senescence, malfunctioning autophagy). Studies applied molecular and analytical methods in aged Fischer 344 rat urothelium. Treatment with 8-AG markedly ameliorated age-related urothelial abnormalities, restoring many parameters to levels comparable to those observed in younger animals. These findings suggest that the deleterious effects of purine dysregulation extend to the bladder urothelium and can be attenuated via gerotherapeutic benefits of 8-AG.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-65316-8.",
  "abstract_shown": true,
  "affiliations": [
    "Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA",
    "Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA",
    "Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA",
    "Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Lori A. Birder"
    },
    {
      "affs": [
        1
      ],
      "name": "Amanda Wolf-Johnston"
    },
    {
      "affs": [
        2
      ],
      "name": "Claudette Marie St Croix"
    },
    {
      "affs": [
        2
      ],
      "name": "Mark A. Ross"
    },
    {
      "affs": [
        2
      ],
      "name": "Simon C. Watkins"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Anthony J. Kanai"
    },
    {
      "affs": [
        3
      ],
      "name": "Dhivyaa Rajasundaram"
    },
    {
      "affs": [
        1
      ],
      "name": "Edwin K. Jackson"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/89jesjv1tmz8v.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-65316-8",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736526/",
  "id": "89jesjv1tmz8v",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://doi.org/10.1038/s41598-026-65316-8",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2748|Urinary Bladder and Prostate Research"
    ]
  ],
  "openalex": "W7172484812",
  "pdf_url": "https://www.nature.com/articles/s41598-026-65316-8_reference.pdf",
  "pmcid": "PMC13736526",
  "pmid": null,
  "published": "2026-08-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/89jesjv1tmz8v.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:57Z",
      "native_id": "PMC13736526",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41598-026-65316-8"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2748|Urinary Bladder and Prostate Research",
      "subfield": "general"
    }
  ],
  "title": "8-aminoguanine as a therapeutic strategy to reverse hallmarks of urothelial cell aging",
  "title_text": "8-aminoguanine as a therapeutic strategy to reverse hallmarks of urothelial cell aging",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:57Z",
  "url": "https://research.draconitic.com/paper/89jesjv1tmz8v",
  "venue": "Scientific Reports",
  "versions": []
}