{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:46:39Z","timestamp":1787323599819,"version":"build-2736575974"},"reference-count":64,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["114\u20102628\u2010B075\u2010B\u2010001\u2010MY3"],"award-info":[{"award-number":["114\u20102628\u2010B075\u2010B\u2010001\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"publisher","award":["KSVGH\u2010114\u2010056"],"award-info":[{"award-number":["KSVGH\u2010114\u2010056"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Metabolic aging underlies a cluster of chronic conditions\u2014type 2 diabetes, cardiovascular disease, sarcopenia, and neurodegeneration\u2014that account for a substantial share of global morbidity and mortality. A common feature is progressive mitochondrial dysfunction: impaired bioenergetics, disrupted quality control, and loss of metabolic resilience. Reduced mitochondrial DNA copy number in peripheral blood leukocytes is associated with cardiometabolic disease and mortality, but pre\u2010analytical variability, dependence on blood\u2010cell composition, and uncertain relationship to tissue\u2010level function mean it should be regarded as a candidate risk\u2010associated biomarker rather than a validated measure of mitochondrial integrity. Glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101 RAs), developed for glycemic control, engage pathways implicated in mitochondrial biogenesis, dynamics, and mitophagy; whether these effects reflect direct receptor signaling, indirect consequences of weight loss, or secondary mediators such as interleukin\u20106 remains debated and appears tissue\u2010dependent. In SELECT, semaglutide reduced major adverse cardiovascular events by 20% in obesity without diabetes, and a 2025 multi\u2010omic study in aged male mice found GLP\u20101 RA treatment attenuated age\u2010associated molecular signatures despite only modest changes in food intake and body weight. No trial, however, has incorporated a prespecified mitochondrial endpoint, human mechanistic evidence remains limited, and access to these therapies remains uneven worldwide. Here we synthesize mechanistic, preclinical, and clinical evidence for a proposed GLP\u20101\u2013mitochondria axis, classify this evidence by receptor dependence and translational stage, distinguish disease\u2010specific treatment effects from evidence for aging modification, examine four major controversies, and outline a research and policy agenda for responsible, evidence\u2010graded development of GLP\u20101\u2010based geroscience interventions.<\/jats:p>","DOI":"10.1111\/acel.70676","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:36:51Z","timestamp":1787024211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>GLP<\/scp>\n                    \u20101\u2013Mitochondria Axis in Metabolic Aging"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1016-2233","authenticated-orcid":false,"given":"Renin","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Medical Education and Research Kaohsiung Veterans General Hospital  Kaohsiung Taiwan"},{"name":"Center of General Education, Cheng Shiu University  Kaohsiung Taiwan"},{"name":"Center of General Education, Shu\u2010Zen Junior College of Medicine and Management  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6400-544X","authenticated-orcid":false,"given":"Andy P.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Sundial Initiative  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3773-9015","authenticated-orcid":false,"given":"Chia\u2010Jung","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Education and Research Kaohsiung Veterans General Hospital  Kaohsiung Taiwan"},{"name":"Center of General Education, Cheng Shiu University  Kaohsiung Taiwan"},{"name":"Center of General Education, Shu\u2010Zen Junior College of Medicine and Management  Kaohsiung Taiwan"},{"name":"Department of Obstetrics and Gynecology Kaohsiung Veterans General Hospital  Kaohsiung Taiwan"},{"name":"Institute of Biopharmaceutical Sciences, National Sun Yat\u2010Sen University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101195"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018\u201000004"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)00516\u20104"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2018.02.010"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(24)00469\u20100"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010010\u20100454\u2010z"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07813"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2024.108028"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020\u2010024\u201000817\u20108"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afy169"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(26)00459\u20109"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010021\u201000524\u2010z"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.03.001"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1196371"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcae208"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/560340"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)30752\u20102"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.18388\/abp.2017_1634"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006373\u20101"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100813"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad403"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.10.014"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206038"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2310645"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.156113"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2025.156463"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.039"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.4735"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2306963"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2313917"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13818"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2026.102665"},{"key":"e_1_2_13_34_1","doi-asserted-by":"crossref","unstructured":"Levi 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