{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:33:35Z","timestamp":1789666415207,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG073181"],"award-info":[{"award-number":["AG073181"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG043490"],"award-info":[{"award-number":["AG043490"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG050886"],"award-info":[{"award-number":["AG050886"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aging is accompanied by profound changes in energy metabolism, yet the underlying drivers and modulators of these shifts remain incompletely understood. Here, we investigated how life\u2010history evolution shapes metabolic aging and pharmacological responsiveness by leveraging\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    <\/jats:styled-content>\n                    lines divergently selected for reproductive timing. We measured organismal oxygen consumption rate and performed untargeted metabolomics in young and old flies of both sexes from long\u2010lived \u201cO\u201d lines (selected for female late\u2010life reproduction) and unselected \u201cB\u201d control lines. Males and females from the O lines maintained stable metabolic rates and largely preserved metabolite profiles with age, whereas B line flies showed age\u2010related increases in oxygen consumption, citrate accumulation, and elevated levels of medium\u2010 and long\u2010chain fatty acids, hallmarks of mitochondrial inefficiency and impaired lipid oxidation. Aged B flies also displayed elevated S\u2010adenosylmethionine, reduced sarcosine, and diminished heme levels, indicating dysregulation of one\u2010carbon metabolism and impaired heme biosynthesis. Furthermore, Vitamin B6 metabolites, pyridoxamine, pyridoxal, and 4\u2010pyridoxate, increased with aging only in B line females. Motivated by evidence implicating the renin\u2010angiotensin system in metabolic aging, we treated flies with the angiotensin\u2010converting enzyme (ACE) inhibitor lisinopril. Lisinopril prevented the age\u2010related rise in metabolic rate in B line females, aligning their metabolic phenotype with that of O line flies. This suggests that ACE inhibition may buffer against age\u2010associated increases in metabolic rate and contribute to enhanced metabolic stability. Our results show that selection for delayed reproduction and increased lifespan modifies age\u2010related metabolic trajectories and modulates physiological responses to pharmacological intervention.\n                  <\/jats:p>","DOI":"10.1111\/acel.70375","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T20:42:21Z","timestamp":1768423341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Selection for Postponed Senescence in\n                    <i>Drosophila melanogaster<\/i>\n                    Reveals Distinct Metabolic Aging Trajectories Modifiable by the Angiotensin\u2010Converting Enzyme Inhibitor Lisinopril"],"prefix":"10.1111","volume":"25","author":[{"given":"Denise","family":"Vecchi\u00e9","sequence":"first","affiliation":[{"name":"Department of Nutrition Sciences University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R. H.","family":"Anholt","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics and Department of Genetics and Biochemistry Clemson University  Greenwood South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudy F. C.","family":"Mackay","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics and Department of Genetics and Biochemistry Clemson University  Greenwood South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6345-7508","authenticated-orcid":false,"given":"Maria","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Nutrition Sciences University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.04.018"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36703"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0138569"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025823"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.16094"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080795"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113351"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.202146"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-018-0562-z"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glz152"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13010143"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04530-x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312562"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204593"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2014.04.008"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evaf082"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2010.12.015"},{"key":"e_1_2_11_19_1","article-title":"Renin\u2010Angiotensin System: Updated Understanding and Role in Physiological and Pathophysiological States","volume":"15","author":"Kanugula A. K.","year":"2023","journal-title":"Cureus"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1979.0083"},{"key":"e_1_2_11_21_1","article-title":"Effect of Methionine Restriction on Aging: Its Relationship to Oxidative Stress","volume":"9","author":"Kitada M.","year":"2021","journal-title":"Biomedicine"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2016.08.001"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2023.01.003"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-34410-6"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9332"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu5093481"},{"key":"e_1_2_11_27_1","volume-title":"Lisinopril","author":"Olvera Lopez E.","year":"2024"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.282277.116"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.58053"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-024-01218-9"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031067"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1558-5646.1984.tb00370.x"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(01)00063-7"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00128238"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251810103"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11933-z"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.21.11168"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.895521"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2023.1277715"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.243030.118"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70375","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70375","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70375","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:00:42Z","timestamp":1773000042000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/acel.70375"],"URL":"https:\/\/doi.org\/10.1111\/acel.70375","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]},"assertion":[{"value":"2025-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70375"}}