{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:05:40Z","timestamp":1784030740651,"version":"3.55.0"},"reference-count":67,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aging accompanies metabolic dysregulation, wherein the liver exhibits high sensitivity to age\u2010related changes. AMP\u2010activated protein kinase \u03b12 (AMPK\u03b12), a key energy metabolism regulator, lacks investigation regarding germline knockout effects on aged liver phosphoproteins. This study investigated germline AMPK\u03b12 knockout effects on aged mouse liver through morphological analysis, Western blot (WB), and phosphoproteomics. AMPK\u03b12 knockout significantly exacerbated glucose\u2010lipid metabolism dysfunction, inflammatory responses, and age\u2010related morphological changes, with enhanced senescent phenotypes validated by WB. Data\u2010independent acquisition (DIA) phosphoproteomic analysis identified 4,448 specific phosphopeptides, among which 316 significantly differentially modified peptides. AMPK\u03b12 knockout enhanced phosphorylation of glucose\u2010lipid metabolism proteins, such as acetyl\u2010CoA carboxylase 1 (\n                    <jats:italic>Acaca<\/jats:italic>\n                    ) at S118, S80, S79, S157, and S117 sites, and genomic instability proteins, such as HSP90\u03b2 (\n                    <jats:italic>Hsp90ab1<\/jats:italic>\n                    ) at S255. Conversely, stress response protein HSP27 (\n                    <jats:italic>Hspb1<\/jats:italic>\n                    ) phosphorylation at S86 was significantly reduced, validated by WB. This study revealed novel molecular signatures of AMPK\u03b12 knockout in exacerbating hepatic aging and metabolic dysfunction, suggesting HSP27 as a potential AMPK\u03b12 downstream effector through site\u2010specific phosphorylation. This work first delineated the phosphoproteomic landscape of aged liver in AMPK\u03b12 knockout mice, establishing foundations for targeting specific protein phosphorylation sites as therapeutic targets for age\u2010related liver diseases.\n                  <\/jats:p>","DOI":"10.1002\/pmic.70162","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:24:57Z","timestamp":1784028297000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Phosphoproteomic Analysis Demonstrates That AMPK\u03b12 Knockout Exacerbates Hepatic Aging in Mice"],"prefix":"10.1002","author":[{"given":"Han","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congmin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhuo","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxian","family":"He","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzheng","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian Min","family":"Ma","sequence":"additional","affiliation":[{"name":"Asian\/Ethnic Health &amp; 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