{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T02:25:03Z","timestamp":1784341503378,"version":"3.55.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2P20GM103432"],"award-info":[{"award-number":["2P20GM103432"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nocturia, defined as waking one or more times per night to urinate, is a prevalent and burdensome condition with few effective treatments. While the primary risk factor for nocturia is advanced age, few preclinical studies have addressed the pathophysiological mechanisms of nocturia in older subjects. Here, we develop a translational model of nocturia using aging mice and a behavioral paradigm that enables circadian assessment of voluntary urination in group-housed animals. We discovered dampened diurnal regulation of urinary behavior in aged mice compared to adult controls. Molecular analyses revealed disrupted diurnal expression of canonical circadian genes in aged mouse kidney and bladder tissues. Notably, we identified age-related loss of diurnal regulation of the bladder mechanosensory ion channel, Piezo1, suggesting a potential mechanism linking circadian disruption to altered bladder sensitivity. Our results reveal a role for circadian dysfunction in age-related nocturia and identify Piezo1 as a promising therapeutic target for chronobiological intervention.<\/jats:p>","DOI":"10.1093\/gerona\/glaf208","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T11:56:04Z","timestamp":1758974164000},"source":"Crossref","is-referenced-by-count":2,"title":["Diurnal regulation of urinary behavior and gene expression in aged mice"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5472-0199","authenticated-orcid":false,"given":"Danielle S","family":"Taylor","sequence":"first","affiliation":[{"name":"Department of Zoology and Physiology, University of Wyoming , Laramie, Wyoming,","place":["United States"]},{"name":"Neuroscience Program, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert A","family":"Allotey","sequence":"additional","affiliation":[{"name":"Neuroscience Program, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Department of Zoology and Physiology, University of Wyoming , Laramie, Wyoming,","place":["United States"]},{"name":"Program in Ecology and Evolution, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushumna B","family":"Satyanarayana","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Program, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharanya S","family":"Bettadapura","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Life Sciences Program, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole R","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Division of Kinesiology and Health, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason G","family":"Landen","sequence":"additional","affiliation":[{"name":"Neuroscience Program, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam C","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Zoology and Physiology, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily E","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Division of Kinesiology and Health, University of Wyoming , Laramie, Wyoming,","place":["United States"]},{"name":"WWAMI UW School of Medicine, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle R","family":"Bruns","sequence":"additional","affiliation":[{"name":"Division of Kinesiology and Health, University of Wyoming , Laramie, Wyoming,","place":["United States"]},{"name":"WWAMI UW School of Medicine, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5700-1774","authenticated-orcid":false,"given":"Nicole L","family":"Bedford","sequence":"additional","affiliation":[{"name":"Department of Zoology and Physiology, University of Wyoming , Laramie, Wyoming,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"2026071704373546900_glaf208-B1","doi-asserted-by":"publisher","first-page":"e81","DOI":"10.1038\/emm.2013.153","article-title":"Presence of multiple peripheral circadian oscillators in the tissues controlling voiding function in mice","volume":"46","author":"Noh","year":"2014","journal-title":"Exp Mol Med."},{"key":"2026071704373546900_glaf208-B2","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1002\/nau.20355","article-title":"Normative bladder diary measurements: night versus day","volume":"26","author":"Parsons","year":"2007","journal-title":"Neurourol Urodyn"},{"key":"2026071704373546900_glaf208-B3","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.juro.2010.04.011","article-title":"The prevalence and causes of nocturia","volume":"184","author":"Bosch","year":"2010","journal-title":"J Urol."},{"key":"2026071704373546900_glaf208-B4","doi-asserted-by":"publisher","first-page":"e27","DOI":"10.1053\/j.ackd.2010.04.004","article-title":"Nocturia and aging: diagnosis and treatment","volume":"17","author":"Boongird","year":"2010","journal-title":"Adv Chronic Kidney Dis."},{"key":"2026071704373546900_glaf208-B5","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.jpsychores.2004.04.003","article-title":"Nocturia, nocturnal polyuria, and sleep quality in the elderly","volume":"56","author":"Asplund","year":"2004","journal-title":"J Psychosom Res."},{"key":"2026071704373546900_glaf208-B6","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1111\/j.1742-1241.2009.02326.x","article-title":"The association of nocturia with incident falls in an elderly community-dwelling cohort","volume":"64","author":"Vaughan","year":"2010","journal-title":"Int J Clin Pract."},{"key":"2026071704373546900_glaf208-B7","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1002\/nau.24711","article-title":"Association of nocturia and cardiovascular disease: data from the National Health and Nutrition Examination Survey","volume":"40","author":"Moon","year":"2021","journal-title":"Neurourol Urodyn"},{"key":"2026071704373546900_glaf208-B8","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1038\/nrurol.2016.134","article-title":"Nocturia: aetiology and treatment in adults","volume":"13","author":"Dani","year":"2016","journal-title":"Nat Rev Urol"},{"key":"2026071704373546900_glaf208-B9","doi-asserted-by":"publisher","first-page":"e13027","DOI":"10.1111\/ijcp.13027","article-title":"A practical approach to the management of nocturia","volume":"71","author":"Oelke","year":"2017","journal-title":"Int J Clin Pract."},{"key":"2026071704373546900_glaf208-B10","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1002\/nau.10053","article-title":"The standardisation of terminology in nocturia: report from the Standardisation Sub-committee of the International Continence Society","volume":"21","author":"Van Kerrebroeck","year":"2002","journal-title":"Neurourol Urodyn"},{"key":"2026071704373546900_glaf208-B11","doi-asserted-by":"publisher","first-page":"R432-R443","DOI":"10.1016\/j.cub.2016.04.011","article-title":"The circadian clock and human health","volume":"26","author":"Roenneberg","year":"2016","journal-title":"Curr Biol."},{"key":"2026071704373546900_glaf208-B12","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.urology.2015.07.047","article-title":"Effect of shift work on nocturia","volume":"87","author":"Kim","year":"2016","journal-title":"Urology."},{"key":"2026071704373546900_glaf208-B13","doi-asserted-by":"publisher","first-page":"e148277","DOI":"10.1172\/JCI148277","article-title":"Circadian rhythms and renal pathophysiology","volume":"132","author":"Mohandas","year":"2022","journal-title":"J Clin Invest"},{"key":"2026071704373546900_glaf208-B14","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1002\/nau.23062","article-title":"The clock mutant mouse is a novel experimental model for nocturia and nocturnal polyuria","volume":"36","author":"Ihara","year":"2017","journal-title":"Neurourol Urodyn."},{"key":"2026071704373546900_glaf208-B15","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/9780470942390.mo140195","article-title":"Aging research using mouse models","volume":"5","author":"Ackert-Bicknell","year":"2015","journal-title":"Curr Protoc Mouse Biol."},{"key":"2026071704373546900_glaf208-B16","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1146\/annurev-animal-022114-110829","article-title":"Animal models of aging research: implications for human aging and age-related diseases","volume":"3","author":"Mitchell","year":"2015","journal-title":"Annu Rev Anim Biosci"},{"key":"2026071704373546900_glaf208-B17","doi-asserted-by":"publisher","first-page":"6179","DOI":"10.1038\/s41598-019-42512-3","article-title":"Standard laboratory housing for mice restricts their ability to segregate space into clean and dirty areas","volume":"9","author":"Makowska","year":"2019","journal-title":"Sci Rep"},{"key":"2026071704373546900_glaf208-B18","doi-asserted-by":"publisher","first-page":"e58460","DOI":"10.1371\/journal.pone.0058460","article-title":"Mice do not habituate to metabolism cage housing\u2014a three week study of male BALB\/c mice","volume":"8","author":"Kalliokoski","year":"2013","journal-title":"PloS One"},{"key":"2026071704373546900_glaf208-B19","doi-asserted-by":"publisher","first-page":"132","DOI":"10.30802\/AALAS-JAALAS-21-000087","article-title":"Short-term housing in metabolic caging on measures of energy and fluid balance in male C57BL\/6J mice (Mus musculus)","volume":"61","author":"Ziegler","year":"2022","journal-title":"J Am Assoc Lab Anim Sci."},{"key":"2026071704373546900_glaf208-B20","doi-asserted-by":"publisher","first-page":"e21200008","DOI":"10.14440\/bladder.2023.870","article-title":"The expression and function of Piezo channels in bladder","volume":"10","author":"Li","year":"2023","journal-title":"Bladder"},{"key":"2026071704373546900_glaf208-B21","doi-asserted-by":"publisher","first-page":"e152984","DOI":"10.1172\/jci.insight.152984","article-title":"Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception","volume":"6","author":"Dalghi","year":"2021","journal-title":"JCI Insight"},{"key":"2026071704373546900_glaf208-B22","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/s41586-020-2830-7","article-title":"PIEZO2 in sensory neurons and urothelial cells coordinates urination","volume":"588","author":"Marshall","year":"2020","journal-title":"Nature."},{"key":"2026071704373546900_glaf208-B23","doi-asserted-by":"publisher","first-page":"F303","DOI":"10.1152\/ajprenal.00214.2019","article-title":"Expression and distribution of PIEZO1 in the mouse urinary tract","volume":"317","author":"Dalghi","year":"2019","journal-title":"Am J Physiol Renal Physiol"},{"key":"2026071704373546900_glaf208-B24","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1002\/nau.23400","article-title":"The circadian expression of Piezo1, TRPV4, Connexin26, and VNUT, associated with the expression levels of the clock genes in mouse primary cultured urothelial cells","volume":"37","author":"Ihara","year":"2018","journal-title":"Neurourol Urodyn."},{"key":"2026071704373546900_glaf208-B25","doi-asserted-by":"publisher","first-page":"e0168234","DOI":"10.1371\/journal.pone.0168234","article-title":"Clock genes regulate the circadian expression of Piezo1, TRPV4, Connexin26, and VNUT in an ex vivo mouse bladder mucosa","volume":"12","author":"Ihara","year":"2017","journal-title":"PLoS One"},{"key":"2026071704373546900_glaf208-B26","doi-asserted-by":"publisher","first-page":"119555","DOI":"10.1016\/j.lfs.2021.119555","article-title":"Different effects of GsMTx4 on nocturia associated with the circadian clock and Piezo1 expression in mice","volume":"278","author":"Ihara","year":"2021","journal-title":"Life Sci."},{"key":"2026071704373546900_glaf208-B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1472-6793-6-1","article-title":"The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa","volume":"6","author":"Saban","year":"2006","journal-title":"BMC Physiol."},{"key":"2026071704373546900_glaf208-B28","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1038\/ncomms1812","article-title":"Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm","volume":"3","author":"Negoro","year":"2012","journal-title":"Nature Commun"},{"key":"2026071704373546900_glaf208-B29","doi-asserted-by":"publisher","first-page":"e2018078118","DOI":"10.1073\/pnas.2018078118","article-title":"Social isolation uncovers a circuit underlying context-dependent territory-covering micturition","volume":"118","author":"Hyun","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026071704373546900_glaf208-B30","doi-asserted-by":"publisher","first-page":"e63425","DOI":"10.7554\/eLife.63425","article-title":"Sex differences in biological aging with a focus on human studies","volume":"10","author":"H\u00e4gg","year":"2021","journal-title":"elife."},{"key":"2026071704373546900_glaf208-B31","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41585-024-00961-0","article-title":"Disruption of circadian rhythm as a potential pathogenesis of nocturia","volume":"22","author":"Song","year":"2025","journal-title":"Nat Rev Urol."},{"key":"2026071704373546900_glaf208-B32","doi-asserted-by":"publisher","first-page":"111982","DOI":"10.1016\/j.celrep.2022.111982","article-title":"Defining the age-dependent and tissue-specific circadian transcriptome in male mice.","volume":"42","author":"Wolff","journal-title":"Cell Rep"},{"key":"2026071704373546900_glaf208-B33","doi-asserted-by":"publisher","first-page":"16193","DOI":"10.1523\/JNEUROSCI.3559-12.2012","article-title":"Aging differentially affects the re-entrainment response of central and peripheral circadian oscillators.","volume":"32","author":"Sellix","year":"2012","journal-title":"J Neurosci."},{"key":"2026071704373546900_glaf208-B34","doi-asserted-by":"publisher","first-page":"e19427","DOI":"10.1016\/j.heliyon.2023.e19427","article-title":"Mechanotransduction in the urothelium: ATP signalling and mechanoreceptors.","volume":"9","author":"Li","journal-title":"Heliyon"},{"key":"2026071704373546900_glaf208-B35","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/s41580-024-00773-5","article-title":"Mechanisms of mechanotransduction and physiological roles of PIEZO channels","volume":"25","author":"Xiao","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026071704373546900_glaf208-B36","doi-asserted-by":"publisher","first-page":"429","DOI":"10.2165\/00002512-199915060-00003","article-title":"Treatment of nocturia in the elderly","volume":"15","author":"Kallas","year":"1999","journal-title":"Drugs Aging."},{"key":"2026071704373546900_glaf208-B37","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1038\/s41598-018-20406-0","article-title":"Age-related changes in function and gene expression of the male and female mouse bladder","volume":"8","author":"Kamei","year":"2018","journal-title":"Sci Rep"},{"key":"2026071704373546900_glaf208-B38","doi-asserted-by":"publisher","first-page":"e13990","DOI":"10.1111\/acel.13990","article-title":"Aging and urinary control: alterations in the brain\u2013bladder axis","volume":"22","author":"Hardy","year":"2023","journal-title":"Aging Cell."},{"key":"2026071704373546900_glaf208-B39","doi-asserted-by":"publisher","first-page":"2775","DOI":"10.1016\/j.cub.2019.07.009","article-title":"Non-Crh glutamatergic neurons in Barrington\u2019s nucleus control micturition via glutamatergic afferents from the midbrain and hypothalamus","volume":"29","author":"Verstegen","year":"2019","journal-title":"Curr Biol"},{"key":"2026071704373546900_glaf208-B40","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1007\/s11096-013-9749-0","article-title":"Timing is important in medication administration: a timely review of chronotherapy research","volume":"35","author":"Kaur","year":"2013","journal-title":"Int J Clin Pharm."}],"container-title":["The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/advance-article-pdf\/doi\/10.1093\/gerona\/glaf208\/64428353\/glaf208.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/80\/12\/glaf208\/64428353\/glaf208.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/80\/12\/glaf208\/64428353\/glaf208.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T08:37:45Z","timestamp":1784277465000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article\/doi\/10.1093\/gerona\/glaf208\/8268001"}},"subtitle":[],"editor":[{"given":"Gustavo","family":"Duque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,29]]},"references-count":40,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,11,6]]}},"URL":"https:\/\/doi.org\/10.1093\/gerona\/glaf208","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.03.16.642675","asserted-by":"object"}]},"ISSN":["1079-5006","1758-535X"],"issn-type":[{"value":"1079-5006","type":"print"},{"value":"1758-535X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,9,29]]},"article-number":"glaf208"}}