8-aminoguanine as a therapeutic strategy to reverse hallmarks of urothelial cell aging (doi:10.7910/DVN/Y1A8XI)

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Document Description

Citation

Title:

8-aminoguanine as a therapeutic strategy to reverse hallmarks of urothelial cell aging

Identification Number:

doi:10.7910/DVN/Y1A8XI

Distributor:

Harvard Dataverse

Date of Distribution:

2026-06-02

Version:

1

Bibliographic Citation:

Wolf-Johnston, Amanda, 2026, "8-aminoguanine as a therapeutic strategy to reverse hallmarks of urothelial cell aging", https://doi.org/10.7910/DVN/Y1A8XI, Harvard Dataverse, V1

Study Description

Citation

Title:

8-aminoguanine as a therapeutic strategy to reverse hallmarks of urothelial cell aging

Identification Number:

doi:10.7910/DVN/Y1A8XI

Authoring Entity:

Wolf-Johnston, Amanda (University of Pittsburgh)

Producer:

Birder, Lori

Distributor:

Harvard Dataverse

Access Authority:

Wolf-Johnston, Amanda

Depositor:

Wolf-Johnston, Amanda

Date of Deposit:

2026-06-01

Holdings Information:

https://doi.org/10.7910/DVN/Y1A8XI

Study Scope

Keywords:

Medicine, Health and Life Sciences

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.

Notes:

Article submission under review.

Methodology and Processing

Sources Statement

Data Access

Notes:

<a href="http://creativecommons.org/publicdomain/zero/1.0">CC0 1.0</a>

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20231005 bgal tiffs only.zip

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Data for upload Sci Reports 0402 2026.xlsx

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