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As a key target of growth hormone (GH), adipose tissue may mediate aging, though the underlying mechanisms remain unclear. We investigated how adipose\u2010specific GHR ablation influences multisystem aging, with a focus on metabolic health and cognitive function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We generated adipose\u2010specific GHR knockout (Ad\u2010GHRKO) mice and assessed healthspan parameters including cognitive function, musculoskeletal integrity and metabolic profiles. Adipose tissue remodelling and inflammation were examined by histology and protein analysis. Subcutaneous white adipose transcriptomics identified gene expression changes. The role of the AMPK\u2010SIRT1\u2010Ac\u2010PPAR\u03b3 pathway in metabolic elasticity and aging was elucidated by Western blot and in\u00a0vitro assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ad\u2010GHRKO mice exhibited extended healthspan, with enhanced cognitive performance, improved muscle strength and bone mass and a lifespan increase trend. Mechanistically, GHR ablation remodelled adipose tissue, reducing age\u2010related lipid redistribution, restoring glucose homeostasis and creating a low\u2010inflammation, high\u2010plasticity depot. This reprogramming boosted systemic metabolic elasticity primarily via AMPK\u2010SIRT1\u2010Ac\u2010PPAR\u03b3 activation. AMPK inhibition abolished benefits, confirming its pivotal role.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings identify adipose\u2010specific GH signalling antagonism as a regulatory switch that recalibrates the local balance between GH and IGF\u20101 actions, thereby reprogramming adipose tissue to promote coordinated systemin metabolic resilience during aging. This tissue\u2010targeted strategy circumvents the developmental and endocrine limitations associated with global GH\/IGF\u20101 suppression. Rather than merely extending lifespan, adipose\u2010specific GHR ablation supports healthier aging by preserving metabolic homeostasis, maintaining multisystem functional integrity and reducing age\u2010associated inflammatory and fibrotic remodelling. Collectively, these results highlight a potentially translatable approach for mitigating age\u2010related metabolic and cognitive decline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70655","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T08:49:16Z","timestamp":1773823756000},"page":"4741-4758","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adipose\u2010Specific\n                    <scp>GHR<\/scp>\n                    Knockout Confers Multidimensional Anti\u2010Aging Advantages via Adipose Tissue Remodelling and Enhanced Metabolic Elasticity"],"prefix":"10.1111","volume":"28","author":[{"given":"Rui","family":"Ma","sequence":"first","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 Dalian Medical University  Dalian China"},{"name":"Key Laboratory of Endocrine Glucose &amp; Lipids Metabolism and Brain Aging, Ministry of Education, Institute of Laboratory Animal Models, Shandong Provincial Hospital Affiliated to Shandong First Medical University Science and Technology Innovation Center, Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan Shandong 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, Institute of Laboratory Animal Models, Shandong Provincial Hospital Affiliated to Shandong First Medical University Science and Technology Innovation Center, Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan Shandong China"},{"name":"Metabolism and Disease Research Center Central Hospital Affiliated to 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