{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:08:02Z","timestamp":1792195682222,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2021209013"],"award-info":[{"award-number":["H2021209013"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2018209341"],"award-info":[{"award-number":["H2018209341"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471022"],"award-info":[{"award-number":["81471022"]}],"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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aging is a major independent risk factor for the development and progression of metabolic dysfunction\u2010associated steatotic liver disease (MASLD); however, effective therapeutic strategies for this population remain limited. Here, we established a model of aging\u2010associated MASLD by subjecting aged mice to a long\u2010term high\u2010fat diet (HFD), which recapitulated key disease features including progressive hepatic steatosis, inflammation, insulin resistance, and fibrosis. A 6\u2010week exercise intervention markedly ameliorated these pathologies by restoring insulin sensitivity and suppressing TGF\u2010\u03b2\/Smad\u2010mediated fibrotic signaling. We identified exercise\u2010derived exosomes (Exercise\u2010Exos) as primary mediators of these benefits. Western blot analysis revealed that extracellular nicotinamide phosphoribosyltransferase (eNAMPT) was markedly enriched in Exercise\u2010Exos compared to those from sedentary controls. Delivery of exosomal eNAMPT activated the hepatic SIRT1\u2010autophagy axis, restored autophagic flux, and inhibited epithelial\u2010mesenchymal transition (EMT). These effects were demonstrated by an increased LC3\u2010II\/LC3\u2010I ratio, reduced p62 accumulation, downregulation of mesenchymal markers (\u03b1\u2010SMA, Vimentin), and upregulation of the epithelial marker\n                    <jats:italic>E<\/jats:italic>\n                    \u2010cadherin. Furthermore, Exercise\u2010Exos treatment significantly reduced collagen deposition. Critically, all protective effects were abolished upon pharmacological inhibition of SIRT1 with EX\u2010527, establishing the necessity of the eNAMPT\u2010NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u2010SIRT1 cascade. Collectively, our results elucidate a novel exosome\u2010mediated pathway through which exercise mitigates age\u2010related liver disease, positioning exosomal eNAMPT as a promising therapeutic agent and exercise mimetic for MASLD.\n                  <\/jats:p>","DOI":"10.1111\/acel.70541","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T04:26:22Z","timestamp":1778473582000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exosome\u2010Delivered\n                    <scp>eNAMPT<\/scp>\n                    From Exercise Activates\n                    <scp>SIRT1<\/scp>\n                    to Counteract Age\u2010Related Hepatic Steatosis and Fibrosis"],"prefix":"10.1111","volume":"25","author":[{"given":"Wenxuan","family":"Song","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences North China University of Science and Technology  Tangshan China"},{"name":"Hebei Key Laboratory of Basic Medical Sciences for Chronic Diseases  Tangshan China"},{"name":"Tangshan Key Laboratory of Basic Research in Medicine Development North China University of Science and Technology  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naijun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology North China University of Science and Technology Affiliated Hospital  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences North China University of Science and Technology  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy North China University of Science and Technology  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy North China University of Science and Technology  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences North China University of Science and Technology  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences North China University of Science and Technology  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Yue","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences North China University of Science and Technology  Tangshan 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Technology  Tangshan China"},{"name":"School of Pharmacy North China University of Science and Technology  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009191"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2020.100086"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.94482"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2024.1365761"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13647"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/831536"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10758"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202434"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.12.013"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.08.037"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms140611963"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/mog.0000000000000176"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.930919"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2013.37.5.315"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.01.011"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102745"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.111002"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj9109"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2024.1480617"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2254191"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2020.100773"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2015.1052180"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029827"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.37349\/eds.2025.100881"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/414799a"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2010.547211"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7142"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006\u20100587"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101312"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2287930"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.12.001"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201001257\u20108"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010020\u201000579\u20105"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010024\u201001481\u20100"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.05.015"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41514\u2010025\u201000297\u2010y"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102014\u2010205740"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15507"}],"container-title":["Aging 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