{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:20:55Z","timestamp":1792815655141,"version":"4.5.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG056944"],"award-info":[{"award-number":["R01 AG056944"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK135076"],"award-info":[{"award-number":["R01 DK135076"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL109002"],"award-info":[{"award-number":["R01 HL109002"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG058814"],"award-info":[{"award-number":["R01AG058814"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R33AG061456"],"award-info":[{"award-number":["R33AG061456"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AG067988"],"award-info":[{"award-number":["P30AG067988"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Lower urinary tract syndrome (LUTS) is a group of urinary tract symptoms and signs that can include urinary incontinence. Advancing age is a major risk factor for LUTS; however, the underlying biochemical mechanisms of age-related LUTS remain unknown. Hypoxanthine (HX) is a purine metabolite associated with generation of tissue-damaging reactive oxygen species (ROS). This study tested the hypothesis that exposure of the adult bladder to HX\u2013ROS over time damages key LUT elements, mimicking qualitatively some of the changes observed with aging.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Adult 3-month-old female Fischer 344 rats were treated with vehicle or HX (10 mg\/kg\/day; 3 weeks) administered in drinking water. Targeted purine metabolomics and molecular approaches were used to assess purine metabolites and biomarkers for oxidative stress and cellular damage. Biomechanical approaches assessed LUT structure and measurements of LUT function (using custom-metabolic cages and cystometry) were also employed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>HX exposure increased biomarkers indicative of oxidative stress, pathophysiological ROS production, and depletion of cellular energy with declines in NAD+ levels. Moreover, HX treatment caused bladder remodeling and decreased the intercontraction interval and leak point pressure (surrogate measure to assess stress urinary incontinence).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These studies provide evidence that in adult rats chronic exposure to HX causes changes in voiding behavior and in bladder structure resembling alterations observed with aging. These results suggest that increased levels of uro-damaging HX were associated with ROS\/oxidative stress-associated cellular damage, which may be central to age-associated development of LUTS, opening up potential opportunities for geroscience-guided interventions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/gerona\/glad171","type":"journal-article","created":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T12:42:14Z","timestamp":1689165734000},"source":"Crossref","is-referenced-by-count":12,"title":["Hypoxanthine Induces Signs of Bladder Aging With Voiding Dysfunction and Lower Urinary Tract Remodeling"],"prefix":"10.1093","volume":"79","author":[{"given":"Lori A","family":"Birder","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania ,","place":["USA"]},{"name":"Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine , Pittsburgh , Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda S","family":"Wolf-Johnston","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Zabbarova","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Materials Science, University of Pittsburgh , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Cardozo","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Materials Science, University of Pittsburgh , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Azari","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Materials Science, University of Pittsburgh , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Kanai","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania ,","place":["USA"]},{"name":"Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine , Pittsburgh , Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A","family":"Kuchel","sequence":"additional","affiliation":[{"name":"UConn Center on Aging, University of Connecticut , Farmington, Connecticut ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin K","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine , Pittsburgh , Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"2025020106153249600_CIT0001","first-page":"S3","article-title":"The definition, prevalence and risk factors for stress urinary incontinence","volume":"6","author":"Luber","year":"2004","journal-title":"Rev 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