{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:56:11Z","timestamp":1790726171219,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC\u2010M302\u2010M3450"],"award-info":[{"award-number":["MC\u2010M302\u2010M3450"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    AMP\u2010activated protein kinase (AMPK) is a key evolutionarily conserved sensor of energy homeostasis and plays a central role in metabolic health and disease. AMPK has also been implicated in ageing; however, most in\u00a0vivo drug studies rely on the use of indirect activators, such as metformin, which have complex modes\u2010of\u2010action, therefore making conclusions on the specific role of AMPK more challenging. Here, we demonstrate that direct activation of AMPK with the compound 991 extends lifespan in\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    <\/jats:styled-content>\n                    and\n                    <jats:italic>Schizosaccharomyces pombe<\/jats:italic>\n                    . In mice, 991 treatment induces a pro\u2010longevity proteomic profile, highlighting the potential for translation to mammals. Overall, our study provides important proof\u2010of\u2010principle for AMPK as a pharmacological target with longevity benefits.\n                  <\/jats:p>","DOI":"10.1111\/acel.70721","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:01:11Z","timestamp":1790722871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Direct Pharmacological Activation of\n                    <scp>AMPK<\/scp>\n                    Extends Lifespan in Yeast, Worms and Flies"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7091-3647","authenticated-orcid":false,"given":"Eliano","family":"dos Santos","sequence":"first","affiliation":[{"name":"MRC Laboratory of Medical Sciences (LMS)  London UK"},{"name":"Institute of Clinical Sciences Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0770-3449","authenticated-orcid":false,"given":"Marie","family":"Blickling","sequence":"additional","affiliation":[{"name":"CECAD Research Cluster University of Cologne  K\u00f6ln Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6681-681X","authenticated-orcid":false,"given":"Fiona C.","family":"Leiper","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Medical Sciences (LMS)  London UK"},{"name":"Institute of Clinical Sciences Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1728-8560","authenticated-orcid":false,"given":"John\u2010Patrick","family":"Alao","sequence":"additional","affiliation":[{"name":"School of Biological and Behavioural Sciences Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5304-5145","authenticated-orcid":false,"given":"Claudia","family":"Lennicke","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Medical Sciences (LMS)  London UK"},{"name":"Institute of Clinical Sciences Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0596-5533","authenticated-orcid":false,"given":"Andrea","family":"Foley","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Medical Sciences (LMS)  London UK"},{"name":"Institute of Clinical Sciences Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5157-5432","authenticated-orcid":false,"given":"Jon R.","family":"Wilson","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5331-639X","authenticated-orcid":false,"given":"Steven J.","family":"Gamblin","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1262-502X","authenticated-orcid":false,"given":"B\u00e9n\u00e9dicte","family":"Chazaud","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoG\u00e8ne, Physiopathologie et G\u00e9n\u00e9tique du Neurone et du Muscle, Universit\u00e9 Claude Bernard Lyon 1, Inserm U1315, CNRS UMR 5261 Universit\u00e9 de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7030-3056","authenticated-orcid":false,"given":"Giovanna","family":"Lollo","sequence":"additional","affiliation":[{"name":"Laboratoire d'Automatique, de G\u00e9nie des Proc\u00e9d\u00e9s et de G\u00e9nie Pharmaceutique, Universit\u00e9 Claude Bernard Lyon 1 CNRS UMR 5007  Villeurbanne France"},{"name":"Institut Universitaire de France (IUF)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3464-3322","authenticated-orcid":false,"given":"R\u00e9mi","family":"Mounier","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoG\u00e8ne, Physiopathologie et G\u00e9n\u00e9tique du Neurone et du Muscle, Universit\u00e9 Claude Bernard Lyon 1, Inserm U1315, CNRS UMR 5261 Universit\u00e9 de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5845-9223","authenticated-orcid":false,"given":"Ga\u00ebtan","family":"Juban","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoG\u00e8ne, Physiopathologie et G\u00e9n\u00e9tique du Neurone et du Muscle, Universit\u00e9 Claude Bernard Lyon 1, Inserm U1315, CNRS UMR 5261 Universit\u00e9 de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4390-0266","authenticated-orcid":false,"given":"Charalampos","family":"Rallis","sequence":"additional","affiliation":[{"name":"School of Biological and Behavioural Sciences Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2316-1830","authenticated-orcid":false,"given":"David","family":"Carling","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Medical Sciences (LMS)  London UK"},{"name":"Institute of Clinical Sciences Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3696-4843","authenticated-orcid":false,"given":"Filipe","family":"Cabreiro","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences Imperial College London  London UK"},{"name":"CECAD Research Cluster University of Cologne  K\u00f6ln Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne  K\u00f6ln Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8637-0042","authenticated-orcid":false,"given":"Helena M.","family":"Cochem\u00e9","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Medical Sciences (LMS)  London UK"},{"name":"Institute of Clinical Sciences Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8101512"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2025.101564"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.17.6625"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1255404"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.08.004"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097\u20100061(199807)14:10<943::AID\u2010YEA292>3.0.CO;2\u2010Y"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.05.011"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.11.010"},{"key":"e_1_2_10_10_1","unstructured":"Boehringer Ingelheim opnMe Website.2024.\u201cAMPK Activator BI\u20109774 Profile.\u201dhttps:\/\/www.opnme.com\/molecules\/ampk\u2010bi\u20109774."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade3332"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.02.004"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010319\u201043589\u20103_10"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.002"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.035"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2017.01.005"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2377"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13264"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.04.010"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv460"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20101253(21)00300\u20109"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1989.tb15185.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010019\u20100638\u2010x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr245"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.59368\/agingbio.20240034"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100474"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1799"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197849"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1385\/1\u201059259\u2010054\u20103:63"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08221"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.165869"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5560"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201060603\u2010w"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010019\u20100157\u20101"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201004431\u20108"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09706"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3192"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah5582"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008758"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20020703"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112396"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2731"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20150497"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pharmtox\u2010010919\u2010023612"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.003"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12080"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44257"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife88229"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.02.058"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E17\u201004\u20100235"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201015346\u20101"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047699"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010019\u20100019\u20102"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.12.006"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3901"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.08.006"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.02.016"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp033"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.09.024"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014\u20105793(96)01209\u20104"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4017"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09932"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100056"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70721","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70721","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70721","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:01:13Z","timestamp":1790722873000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":63,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/acel.70721"],"URL":"https:\/\/doi.org\/10.1111\/acel.70721","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"2026-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70721"}}