{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:47:12Z","timestamp":1787323632677,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U25A2034"],"award-info":[{"award-number":["U25A2034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82500842"],"award-info":[{"award-number":["82500842"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270734"],"award-info":[{"award-number":["82270734"]}],"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":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Sepsis\u2010associated acute kidney injury (SA\u2010AKI) is a common and devastating disease that has a significantly higher incidence and greater severity in elderly patients, but the molecular basis underlying SA\u2010AKI in the elderly is largely unknown. Recent studies have proved autophagy as an intrinsic protective mechanism against AKI; however, the role and regulation of autophagy in aging kidneys remain unclear. Here we demonstrate that defective autophagy activation in aging kidneys is a key to their susceptibility to SA\u2010AKI. In our experiments, the ability of autophagy activation was impaired in aging kidneys in response to SA\u2010AKI in mice. In\u00a0vitro, activation of autophagy with TAT\u2010Beclin\u20101 peptide mitigated lipopolysaccharide (LPS)\u2010induced apoptosis and inflammation in senescent renal proximal tubular cells. Single\u2010cell sequencing revealed significant age\u2010related alterations in autophagy\u2010associated genes in septic AKI, including TFEB. Overexpression of TFEB could partially restore autophagic activity in senescent renal tubular cells and protect them from LPS\u2010induced damage. Moreover, in\u00a0vivo treatment with the curcumin analog C1 (a TFEB activator) enhanced autophagic function in aging kidneys and reduced LPS\u2010induced AKI. These results demonstrate the defective autophagy activation in aging kidneys, which contributes to the SA\u2010AKI sensitivity and susceptibility in the elderly, suggesting a therapeutic strategy by enhancing autophagy.<\/jats:p>","DOI":"10.1111\/acel.70644","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:23:21Z","timestamp":1784661801000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Down\u2010Regulation of\n                    <scp>TFEB<\/scp>\n                    With Defective Autophagy in the Susceptibility of Aging Kidneys to Septic Acute Kidney Injury"],"prefix":"10.1111","volume":"25","author":[{"given":"Yu","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6711-4016","authenticated-orcid":false,"given":"Juan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Medicin The Second Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification The Second Xiangya Hospital of Central South University  Changsha China"},{"name":"Department of Cellular Biology and Anatomy Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center  Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101985"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010021\u201000098\u20104"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010025\u201001030\u20104"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3740"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022111241"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00114"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u201000314\u2010w"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018121251"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.07.013"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255\u2010020\u201002482\u20102"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101151"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000809"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017040421"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012080800"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010022\u201000601\u2010z"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1896906"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.261"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150001"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201003865\u20108"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.166643"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2025.2551683"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2072054"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.10.028"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2021.12.012"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep22171"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13004"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2023.02.005"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00184.2018"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201008729\u20106"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201005862\u20106"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015121308"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25115924"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0000000000001088"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20230140"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.07.030"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204592"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2020.8043"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1179404"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201019350\u2010w"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010020\u20100309\u20102"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.7.813"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13193"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.22931"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24033028"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2019.110591"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI121859"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1159\/000484629"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkac059"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010024\u201000868\u20104"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1159376"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201017985\u2010w"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1824694"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00128"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.44051"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70644","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70644","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:11:15Z","timestamp":1787321475000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":55,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/acel.70644"],"URL":"https:\/\/doi.org\/10.1111\/acel.70644","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"assertion":[{"value":"2026-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70644"}}