{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T01:24:41Z","timestamp":1793928281821,"version":"4.8.0"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515012637"],"award-info":[{"award-number":["2022A1515012637"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873613"],"award-info":[{"award-number":["81873613"]}],"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":["82170762"],"award-info":[{"award-number":["82170762"]}],"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":["82370746"],"award-info":[{"award-number":["82370746"]}],"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":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Renal aging, marked by the accumulation of senescent cells and chronic low\u2010grade inflammation, leads to renal interstitial fibrosis and impaired function. In this study, we investigate the role of macrophages, a key regulator of inflammation, in renal aging by analyzing kidney single\u2010cell RNA sequencing data of C57BL\/6J mice from 8\u2009weeks to 24\u2009months. Our findings elucidate the dynamic changes in the proportion of kidney cell types during renal aging and reveal that increased macrophage infiltration contributes to chronic low\u2010grade inflammation, with these macrophages exhibiting senescence and activation of ferroptosis signaling. CellChat analysis indicates enhanced communications between macrophages and tubular cells during aging. Suppressing ferroptosis alleviates macrophage\u2010mediated tubular partial epithelial\u2010mesenchymal transition in\u00a0vitro, thereby mitigating the expression of fibrosis\u2010related genes. Using SCENIC analysis, we infer Stat1 as a key age\u2010related transcription factor promoting iron dyshomeostasis and ferroptosis in macrophages by regulating the expression of Pcbp1, an iron chaperone protein that inhibits ferroptosis. Furthermore, through virtual screening and molecular docking from a library of anti\u2010aging compounds, we construct a docking model targeting Pcbp1, which indicates that the natural small molecule compound Rutin can suppress macrophage senescence and ferroptosis by preserving Pcbp1. In summary, our study underscores the crucial role of macrophage iron dyshomeostasis and ferroptosis in renal aging. Our results also suggest Pcbp1 as an intervention target in aging\u2010related renal fibrosis and highlight Rutin as a potential therapeutic agent in mitigating age\u2010related renal chronic low\u2010grade inflammation and fibrosis.<\/jats:p>","DOI":"10.1111\/acel.14275","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T08:05:43Z","timestamp":1721203543000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Macrophage iron dyshomeostasis promotes aging\u2010related renal fibrosis"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0219-2056","authenticated-orcid":false,"given":"Lingzhi","family":"Wu","sequence":"first","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchun","family":"Lin","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaomin","family":"Li","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuebo","family":"Huang","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Shu","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Luo","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Liang","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyan","family":"Lai","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialing","family":"Rao","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyong","family":"Hu","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine Baylor College of Medicine  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0220-3616","authenticated-orcid":false,"given":"Hui","family":"Peng","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, the Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"NHC Key Laboratory of Clinical Nephrology (Sun Yat\u2010sen University) and Guangdong Provincial Key Laboratory of Nephrology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2023.122125"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2020.03.014"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.05.027"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154700"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.07.023"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141848"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101151"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04247-9"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3901"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06373-1"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2012.09.003"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13982"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-021-09666-1"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00664-z"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15410"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5FO01036E"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01502-8"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017050574"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00928-2"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03160-0"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6904"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2433987100"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjamd.2016.18"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41683-y"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.811518"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.10.411"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31328"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2FO03301A"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0185-9"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.02.036"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1157643"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44490"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.79196"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.18.9866"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0590-4"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11030359"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.12.007"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14-1225"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-021-00116-6"},{"key":"e_1_2_11_41_1","article-title":"Construction of a cross\u2010species cell landscape at single\u2010cell level","volume":"51","author":"Wang R.","year":"2023","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1255354"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.82352"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.01.015"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101510"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102175"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16857"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1670"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.14275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T06:13:32Z","timestamp":1731564812000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.14275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,17]]},"references-count":47,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/acel.14275"],"URL":"https:\/\/doi.org\/10.1111\/acel.14275","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,17]]},"assertion":[{"value":"2023-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14275"}}