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Although systemic suppression of growth hormone (GH)\/insulin\u2010like growth factor\u20101 (IGF\u20101) signaling has been shown to extend lifespan and enhance cognitive function, the specific role of GH signaling in adipose tissue during brain aging remains unclear. In this study, we used aged (18\u201324\u2009months) adipose\u2010specific GH receptor knockout (Ad\u2010GHRKO) mice and their littermate controls to investigate this relationship. We found that deletion of GHR in adipose tissue significantly attenuated key features of brain aging. Aged Ad\u2010GHRKO mice exhibited reduced neuronal loss in the cortex and hippocampus, diminished neuroinflammation, decreased cellular senescence, and lower levels of tau phosphorylation in the hippocampus compared to controls. Additionally, synaptic integrity, indicated by hippocampal PSD95 expression, and cortical neuronal excitability were preserved. Importantly, Ad\u2010GHRKO mice showed improved cognitive performance across multiple domains, including recognition memory (novel object recognition, NOR), working memory (Y\u2010maze), spatial learning\/memory (Morris water maze), and associative fear memory (passive avoidance). These findings suggest adipose GH signaling as a previously unrecognized peripheral regulator of brain aging and cognition, implicating adipose GHR as a therapeutic target for mitigating age\u2010related cognitive decline.<\/jats:p>","DOI":"10.1111\/acel.70407","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T04:35:25Z","timestamp":1770957325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adipose\u2010Specific\n                    <scp>GHR<\/scp>\n                    Deletion Attenuates Brain Aging and Cognitive Decline in Aged Mice"],"prefix":"10.1111","volume":"25","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology &amp; Visual Science Key Laboratory  Beijing China"},{"name":"Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases Dalian Medical University  Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute for Genome Engineered Animal Models of Human Diseases, National Center of Genetically Engineered Animal Models for International Research, Liaoning Province Key Lab of Genetically Engineered Animal Models Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases Dalian Medical University  Dalian Liaoning China"},{"name":"Key Laboratory of Endocrine Glucose &amp; Lipids Metabolism and Brain Aging, Ministry of Education Shandong Provincial Hospital Affiliated to Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"He","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases Dalian Medical University  Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Ran","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrine Glucose &amp; Lipids Metabolism and Brain Aging, Ministry of Education Shandong Provincial Hospital Affiliated to Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan Shandong China"},{"name":"Metabolism and Disease Research Center Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan Shandong 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