{"id":"https://openalex.org/W7162777029","doi":"https://doi.org/10.7554/elife.111611.1","title":"Decoupling AMPK from fatty acid synthesis allows maintenance of fitness late in life","display_name":"Decoupling AMPK from fatty acid synthesis allows maintenance of fitness late in life","publication_year":2026,"publication_date":"2026-05-29","ids":{"openalex":"https://openalex.org/W7162777029","doi":"https://doi.org/10.7554/elife.111611.1"},"language":null,"primary_location":{"id":"doi:10.7554/elife.111611.1","doi":"https://doi.org/10.7554/elife.111611.1","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.111611.1","pdf_url":null,"source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-2","ki-jl-2","medline","norway-2"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"eLife","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.7554/elife.111611.1","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5065521747","display_name":"Hanane Hadj\u2010Moussa","orcid":"https://orcid.org/0000-0002-3338-9046","observed_orcids":["https://orcid.org/0000-0002-3338-9046"]},"institutions":[{"id":"https://openalex.org/I1302113299","display_name":"Babraham Institute","ror":"https://ror.org/01d5qpn59","country_code":"GB","type":"facility","lineage":["https://openalex.org/I1302113299","https://openalex.org/I2799693246","https://openalex.org/I4210087105"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Hanane Hadj-Moussa","raw_affiliation_strings":["Epigenetics Programme, Babraham Institute"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Epigenetics Programme, Babraham Institute","institution_ids":["https://openalex.org/I1302113299"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5116844917","display_name":"Megan Ulusan","orcid":"https://orcid.org/0009-0001-0569-3403","observed_orcids":["https://orcid.org/0009-0001-0569-3403"]},"institutions":[{"id":"https://openalex.org/I1302113299","display_name":"Babraham Institute","ror":"https://ror.org/01d5qpn59","country_code":"GB","type":"facility","lineage":["https://openalex.org/I1302113299","https://openalex.org/I2799693246","https://openalex.org/I4210087105"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Megan Ulusan","raw_affiliation_strings":["Epigenetics Programme, Babraham Institute"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Epigenetics Programme, Babraham Institute","institution_ids":["https://openalex.org/I1302113299"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061028677","display_name":"Dorottya Horkai","orcid":"https://orcid.org/0000-0001-9430-1864","observed_orcids":["https://orcid.org/0000-0001-9430-1864"]},"institutions":[{"id":"https://openalex.org/I1302113299","display_name":"Babraham Institute","ror":"https://ror.org/01d5qpn59","country_code":"GB","type":"facility","lineage":["https://openalex.org/I1302113299","https://openalex.org/I2799693246","https://openalex.org/I4210087105"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Dorottya Horkai","raw_affiliation_strings":["Epigenetics Programme, Babraham Institute","ZOMP, Cavendish Laboratory"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Epigenetics Programme, Babraham Institute","institution_ids":["https://openalex.org/I1302113299"]},{"raw_affiliation_string":"ZOMP, Cavendish Laboratory","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5146586717","display_name":"Mohammed Kamran Afzal Mirza","orcid":"https://orcid.org/0009-0008-2467-4882","observed_orcids":["https://orcid.org/0009-0008-2467-4882"]},"institutions":[{"id":"https://openalex.org/I1302113299","display_name":"Babraham Institute","ror":"https://ror.org/01d5qpn59","country_code":"GB","type":"facility","lineage":["https://openalex.org/I1302113299","https://openalex.org/I2799693246","https://openalex.org/I4210087105"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Mohammed Kamran Afzal Mirza","raw_affiliation_strings":["Epigenetics Programme, Babraham Institute"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Epigenetics Programme, Babraham Institute","institution_ids":["https://openalex.org/I1302113299"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5023627324","display_name":"Jonathan M. Houseley","orcid":"https://orcid.org/0000-0001-8509-1500","observed_orcids":["https://orcid.org/0000-0001-8509-1500"]},"institutions":[{"id":"https://openalex.org/I1302113299","display_name":"Babraham Institute","ror":"https://ror.org/01d5qpn59","country_code":"GB","type":"facility","lineage":["https://openalex.org/I1302113299","https://openalex.org/I2799693246","https://openalex.org/I4210087105"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Jonathan Houseley","raw_affiliation_strings":["Epigenetics Programme, Babraham Institute"],"raw_orcid":"https://orcid.org/0000-0001-8509-1500","affiliations":[{"raw_affiliation_string":"Epigenetics Programme, Babraham Institute","institution_ids":["https://openalex.org/I1302113299"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I1302113299"],"apc_list":{"value":3000,"currency":"USD","value_usd":2500},"apc_paid":{"value":3000,"currency":"USD","value_usd":2500},"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10676","display_name":"Genetics, Aging, and Longevity in Model Organisms","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/1302","display_name":"Aging"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10676","display_name":"Genetics, Aging, and Longevity in Model Organisms","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/1302","display_name":"Aging"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11339","display_name":"Metabolism, Diabetes, and Cancer","score":0.0010999999940395355,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10937","display_name":"Telomeres, Telomerase, and Senescence","score":0.0006000000284984708,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/ampk","display_name":"AMPK","score":0.9390000104904175},{"id":"https://openalex.org/keywords/fatty-acid-synthesis","display_name":"fatty acid synthesis","score":0.8019999861717224},{"id":"https://openalex.org/keywords/senescence","display_name":"senescence","score":0.9039999842643738},{"id":"https://openalex.org/keywords/acetyl-coa-metabolism","display_name":"acetyl-CoA metabolism","score":0.9169999957084656},{"id":"https://openalex.org/keywords/saccharomyces-cerevisiae","display_name":"Saccharomyces cerevisiae","score":0.656000018119812},{"id":"https://openalex.org/keywords/metabolic-heterogeneity","display_name":"metabolic heterogeneity","score":0.550000011920929}],"concepts":[{"id":"https://openalex.org/C2780124434","wikidata":"https://www.wikidata.org/wiki/Q12357464","display_name":"AMPK","level":4,"score":0.819599986076355},{"id":"https://openalex.org/C522857546","wikidata":"https://www.wikidata.org/wiki/Q2070979","display_name":"Senescence","level":2,"score":0.7610999941825867},{"id":"https://openalex.org/C500499127","wikidata":"https://www.wikidata.org/wiki/Q332154","display_name":"Ageing","level":2,"score":0.730400025844574},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5393000245094299},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5146999955177307},{"id":"https://openalex.org/C543025807","wikidata":"https://www.wikidata.org/wiki/Q61476","display_name":"Fatty acid","level":2,"score":0.4375},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4277999997138977},{"id":"https://openalex.org/C98539663","wikidata":"https://www.wikidata.org/wiki/Q220599","display_name":"Cytosol","level":3,"score":0.3878999948501587},{"id":"https://openalex.org/C2776780712","wikidata":"https://www.wikidata.org/wiki/Q295240","display_name":"AMP-activated protein kinase","level":5,"score":0.36419999599456787},{"id":"https://openalex.org/C98490376","wikidata":"https://www.wikidata.org/wiki/Q14876060","display_name":"mTORC1","level":4,"score":0.31470000743865967},{"id":"https://openalex.org/C2779123261","wikidata":"https://www.wikidata.org/wiki/Q407635","display_name":"Coenzyme A","level":4,"score":0.3125},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.31049999594688416},{"id":"https://openalex.org/C203522944","wikidata":"https://www.wikidata.org/wiki/Q288322","display_name":"Autophagy","level":3,"score":0.3034999966621399},{"id":"https://openalex.org/C2776759703","wikidata":"https://www.wikidata.org/wiki/Q1066907","display_name":"Longevity","level":2,"score":0.3000999987125397},{"id":"https://openalex.org/C2776941171","wikidata":"https://www.wikidata.org/wiki/Q900209","display_name":"Fatty acid synthesis","level":3,"score":0.30000001192092896},{"id":"https://openalex.org/C4733338","wikidata":"https://www.wikidata.org/wiki/Q2792936","display_name":"Lipid metabolism","level":2,"score":0.29589998722076416},{"id":"https://openalex.org/C19843653","wikidata":"https://www.wikidata.org/wiki/Q213907","display_name":"Model organism","level":3,"score":0.29580000042915344},{"id":"https://openalex.org/C192989942","wikidata":"https://www.wikidata.org/wiki/Q68685","display_name":"Metabolic pathway","level":3,"score":0.2793000042438507},{"id":"https://openalex.org/C82714985","wikidata":"https://www.wikidata.org/wiki/Q306213","display_name":"Beta oxidation","level":3,"score":0.26649999618530273},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.2662000060081482},{"id":"https://openalex.org/C169822122","wikidata":"https://www.wikidata.org/wiki/Q230187","display_name":"Crosstalk","level":2,"score":0.26080000400543213},{"id":"https://openalex.org/C2780104201","wikidata":"https://www.wikidata.org/wiki/Q130888","display_name":"Drosophila melanogaster","level":3,"score":0.2538999915122986},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.25110000371932983}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.7554/elife.111611.1","doi":"https://doi.org/10.7554/elife.111611.1","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.111611.1","pdf_url":null,"source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-2","ki-jl-2","medline","norway-2"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"eLife","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.7554/elife.111611.1","doi":"https://doi.org/10.7554/elife.111611.1","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.111611.1","pdf_url":null,"source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-2","ki-jl-2","medline","norway-2"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"eLife","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.6240000128746033,"display_name":"Good health and well-being"}],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":87,"referenced_works":["https://openalex.org/W1536128494","https://openalex.org/W1599051410","https://openalex.org/W1606049883","https://openalex.org/W1908925080","https://openalex.org/W1949673751","https://openalex.org/W1958996383","https://openalex.org/W1966072209","https://openalex.org/W1966132436","https://openalex.org/W1967330678","https://openalex.org/W1970998722","https://openalex.org/W1976070371","https://openalex.org/W1977466283","https://openalex.org/W1986148031","https://openalex.org/W1990048596","https://openalex.org/W1992663222","https://openalex.org/W1993091967","https://openalex.org/W2004401468","https://openalex.org/W2006022142","https://openalex.org/W2006776535","https://openalex.org/W2006806054","https://openalex.org/W2007622308","https://openalex.org/W2009810346","https://openalex.org/W2010933392","https://openalex.org/W2014287442","https://openalex.org/W2019677361","https://openalex.org/W2021469756","https://openalex.org/W2028786309","https://openalex.org/W2037918682","https://openalex.org/W2038963685","https://openalex.org/W2053493267","https://openalex.org/W2058713768","https://openalex.org/W2059825898","https://openalex.org/W2062258025","https://openalex.org/W2063087406","https://openalex.org/W2064885353","https://openalex.org/W2067346106","https://openalex.org/W2071838425","https://openalex.org/W2072130124","https://openalex.org/W2094511058","https://openalex.org/W2101468528","https://openalex.org/W2102278945","https://openalex.org/W2110065044","https://openalex.org/W2111322904","https://openalex.org/W2114512247","https://openalex.org/W2115168068","https://openalex.org/W2119475286","https://openalex.org/W2130016073","https://openalex.org/W2132015995","https://openalex.org/W2135636602","https://openalex.org/W2136998622","https://openalex.org/W2138416557","https://openalex.org/W2149730004","https://openalex.org/W2152239989","https://openalex.org/W2154046032","https://openalex.org/W2157618287","https://openalex.org/W2162023120","https://openalex.org/W2164361361","https://openalex.org/W2169875902","https://openalex.org/W2170549904","https://openalex.org/W2186330137","https://openalex.org/W2290476528","https://openalex.org/W2557455152","https://openalex.org/W2591945221","https://openalex.org/W2605338423","https://openalex.org/W2615811947","https://openalex.org/W2625887862","https://openalex.org/W2763871199","https://openalex.org/W2784117710","https://openalex.org/W2791490451","https://openalex.org/W2884617799","https://openalex.org/W2921688087","https://openalex.org/W2950604766","https://openalex.org/W2960230553","https://openalex.org/W2972507024","https://openalex.org/W2992097690","https://openalex.org/W3043302462","https://openalex.org/W3088277963","https://openalex.org/W3187589847","https://openalex.org/W4211127285","https://openalex.org/W4294796007","https://openalex.org/W4298151148","https://openalex.org/W4367173695","https://openalex.org/W4368374116","https://openalex.org/W4385737526","https://openalex.org/W4386242078","https://openalex.org/W4386249403","https://openalex.org/W4394955232"],"related_works":[],"abstract_inverted_index":{"Although":[0],"lifespan":[1],"has":[2,134],"long":[3],"been":[4],"the":[5,25,70,125],"focus":[6],"of":[7,27,63,96,128,164,181],"ageing":[8,34,71,97,129,165,192],"research,":[9],"preventing":[10],"functional":[11,77],"decline":[12],"late":[13,217],"in":[14,35,86,124,161,183,202,218],"life":[15],"is":[16,193],"a":[17,40],"more":[18],"pressing":[19],"societal":[20],"need.":[21],"Here,":[22],"we":[23,141],"investigate":[24],"basis":[26],"senescence":[28,56,157,182],"and":[29,38,73,76,137,158,172,204],"declining":[30,198],"fitness":[31,46,102,160,212],"during":[32],"replicative":[33],"budding":[36],"yeast,":[37,203],"describe":[39],"metabolic":[41,209],"perturbation":[42],"that":[43,55,106,143,191,205],"preserves":[44],"late-life":[45],"even":[47],"on":[48],"an":[49],"unrestricted":[50],"glucose":[51],"diet.":[52],"We":[53,167],"show":[54,142],"can":[57],"be":[58,214],"prevented":[59],"by":[60],"constitutive":[61,144],"activation":[62],"AMPK,":[64],"though":[65],"only":[66],"for":[67],"approximately":[68],"half":[69],"population,":[72],"use":[74],"genetic":[75],"assays":[78],"to":[79,121,213],"link":[80],"this":[81],"heterogeneous":[82],"response":[83],"with":[84,197],"differences":[85],"cytosolic":[87,108],"acetyl":[88,174],"coenzyme":[89,175],"A":[90,176],"(Acetyl-CoA)":[91],"metabolism.":[92],"In":[93],"one":[94],"class":[95,127],"cell,":[98],"AMPK":[99,113,132,145],"activity":[100,133,146],"maintains":[101,159],"late-in-life":[103],"through":[104],"pathways":[105,210],"transport":[107],"Acetyl-CoA":[109],"into":[110],"mitochondria,":[111],"but":[112,140],"also":[114],"inhibits":[115],"fatty":[116,149],"acid":[117,150],"synthesis":[118,151],"which":[119],"leads":[120],"lipid":[122,170],"starvation":[123,171],"other":[126],"cell.":[130,166],"Therefore,":[131],"both":[135,162],"positive":[136],"negative":[138],"effects,":[139],"uncoupled":[147],"from":[148],"inhibition":[152],"(the":[153],"A2A":[154],"mutant)":[155],"suppresses":[156],"classes":[163],"further":[168],"implicate":[169],"excess":[173],"availability":[177],"as":[178],"major":[179],"drivers":[180],"replicatively":[184],"aged":[185],"wild-type":[186],"yeast.":[187],"Our":[188],"work":[189],"shows":[190],"not":[194],"intrinsically":[195],"associated":[196],"fitness,":[199],"at":[200],"least":[201],"re-engineering":[206],"highly":[207],"conserved":[208],"allows":[211],"preserved":[215],"very":[216],"life.":[219]},"counts_by_year":[],"updated_date":"2026-09-29T14:09:16.559479","created_date":"2026-05-30T00:00:00"}