{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:28:52Z","timestamp":1793413732120,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7202078"],"award-info":[{"award-number":["7202078"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071133"],"award-info":[{"award-number":["82071133"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The current mechanism by which aging reduces salivary secretion is unknown. This study investigates the mechanism of aging\u2010related submandibular (SMG) dysfunction and evaluates the therapeutic potential of dental pulp stem cell\u2010derived exosomes (DPSC\u2010exos). We found that the stimulated salivary flow rate was significantly reduced in naturally aging and D\u2010galactose\u2010induced aging mice (D\u2010gal mice) compared to control mice. Acinar atrophy and periductal fibrosis in SMGs and parotid glands (PGs) were observed in naturally aging and D\u2010gal mice, whereas sublingual glands (SLGs) had no notable alterations. We observed the accumulation of senescent cells in the SMGs, along with a decrease in claudin\u20103 (Cldn\u20103) expression and alterations in the distribution of Cldn1 and Cldn3. Additionally, after D\u2010gal\u2010induced senescence of SMG\u2010C6 cells, there was a decrease in paracellular pathway permeability, reduced expression of Cldn3 and occludin, and changes in the distribution of Cldn1, 3, 4, and 7. Furthermore, injecting DPSC\u2010exos into the SMGs of D\u2010gal mice improved stimulated salivary flow rate, reduced acinar atrophy, and decreased SA\u2010\u03b2\u2010gal activity. Our study identified that increased senescence of SMGs in aging mice can cause a decrease in salivary secretion by disrupting the expression and distribution of tight junction molecules, and injection of DPSC\u2010exos ameliorates SMG secretory dysfunction. These findings may provide new clues to novel therapeutic targets for aging\u2010related dysfunction of SMGs.<\/jats:p>","DOI":"10.1111\/acel.14470","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T01:44:42Z","timestamp":1736473482000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cellular Senescence Contributes to the Dysfunction of Tight Junctions in Submandibular Glands of Aging Mice"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6599-8725","authenticated-orcid":false,"given":"Zhuo","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology Peking University School of Basic Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian\u2010Ying","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie\u2010Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Xiao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Feng","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Yi","family":"Fan","sequence":"additional","affiliation":[{"name":"Beijing no.161 High School  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Gang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo\u2010Lan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology Peking University School of Basic Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2023.2211203"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.13652"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.05.006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.122.040578"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522\u2010019\u201009837\u2010y"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16932"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2016.1162348"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100543\u2010y"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11091418"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00020.2018"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/md19020114"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6659"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clindermatol.2019.04.009"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000002610"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2016.12.011"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010023\u201004198\u20100"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.13203"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4324"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.07.013"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515570943"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010020\u201003253\u20108"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17010098"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14223"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2010.07.014"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10735\u2010019\u201009854\u20108"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00299.2010"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522\u2010019\u201009797\u20103"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2020.151108"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0003\u20109969(97)00088\u20105"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2017.1343172"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2019.06.016"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2014.06.004"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115835"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00116.2003"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14476"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.871096"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jtxs.12356"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glw154"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010018\u20100092\u20109"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.115.010835"},{"issue":"1","key":"e_1_2_9_44_1","first-page":"13","article-title":"Tight Junctions and Paracellular Fluid and Ion Transport in Salivary Glands","volume":"16","author":"Zhang G. H.","year":"2013","journal-title":"Chinese Journal of Dental Research"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci158450"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516634647"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.14470","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T21:25:18Z","timestamp":1757107518000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.14470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/acel.14470"],"URL":"https:\/\/doi.org\/10.1111\/acel.14470","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,9]]},"assertion":[{"value":"2024-08-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14470"}}