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Recently, the liver's immunological functions have gradually been unveiled: combating pathogens and maintaining tissue homeostasis. Age\u2010related functional alterations in these immune cells emerge as potential drivers of hepatic dysfunction and age\u2010associated pathologies. However, systematic investigations into spatiotemporal immune cell dynamics during liver aging remain limited. To address this gap, we analyzed young and old mouse livers using single\u2010cell\/nuclei and spatial transcriptomics, revealing T cells as the immune cell population with the most pronounced transcriptomic alterations, marked by enrichment of exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in aged livers. Spatial mapping showed exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells accumulating in portal vein (PV) zone, co\u2010localizing with periportal hepatocytes (PP hepatocytes). Up\u2010regulation of LPIN1 in PP hepatocyte promoted T cell exhaustion. CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell exhaustion was tightly associated with disease progression. Therefore, our findings suggest that targeting LPIN1 may alleviate T cell exhaustion, offering potential therapeutic strategies for age\u2010related liver diseases.\n                  <\/jats:p>","DOI":"10.1111\/acel.70482","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T05:30:33Z","timestamp":1776749433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal Transcriptomics Characterizes Immune Microenvironment During Mouse Liver Aging"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1582-3729","authenticated-orcid":false,"given":"Jiahua","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Huazhong University of Science and Technology  Wuhan Hubei 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Peking University  Beijing China"},{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Gastrointestinal Surgery Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Center for Bioinformatics, Center for Statistical Science Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Huazhong University of Science and Technology  Wuhan Hubei China"},{"name":"Institute of Pathology, Tongji Hospital Huazhong University of Science and Technology  Wuhan Hubei 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