{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:25:41Z","timestamp":1772252741438,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T00:00:00Z","timestamp":1540512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK079626"],"award-info":[{"award-number":["P30 DK079626"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AG013280"],"award-info":[{"award-number":["P30 AG013280"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG049494"],"award-info":[{"award-number":["R01 AG049494"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 AG000057"],"award-info":[{"award-number":["T32 AG000057"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS1561814"],"award-info":[{"award-number":["DMS1561814"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug\u2019s impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.<\/jats:p>","DOI":"10.3390\/ijms19113351","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T10:51:01Z","timestamp":1540551061000},"page":"3351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster"],"prefix":"10.3390","volume":"19","author":[{"given":"Karis A.","family":"Ederer","sequence":"first","affiliation":[{"name":"Departments of Nutrition Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Department of Kinesiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Department of Physical Therapy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Bouslog","sequence":"additional","affiliation":[{"name":"Departments of Nutrition Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory S.","family":"Gorman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical, Social and Administrative Sciences, Samford University, Birmingham, AL 35229, USA"},{"name":"Pharmaceutical Sciences Research Institute, Samford University, Birmingham, AL 35229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn C.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Abadir","sequence":"additional","affiliation":[{"name":"Division of Geriatric Medicine and Gerontology, Johns Hopkins School of Medicine, Baltimore, MD 21234, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2467-8118","authenticated-orcid":false,"given":"Daniel","family":"Raftery","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Pain Medicine, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-4187","authenticated-orcid":false,"given":"Douglas","family":"Moellering","sequence":"additional","affiliation":[{"name":"Departments of Nutrition Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Promislow","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Washington, Seattle, WA 98195, USA"},{"name":"Department of Biology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Jumbo-Lucioni","sequence":"additional","affiliation":[{"name":"Departments of Nutrition Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Department of Pharmaceutical, Social and Administrative Sciences, Samford University, Birmingham, AL 35229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6345-7508","authenticated-orcid":false,"given":"Maria","family":"De Luca","sequence":"additional","affiliation":[{"name":"Departments of Nutrition Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1161\/01.CIR.87.6.1816","article-title":"Molecular biology of the renin-angiotensin system","volume":"87","author":"Griendling","year":"1993","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cger.2010.08.004","article-title":"The frail renin-angiotensin system","volume":"27","author":"Abadir","year":"2011","journal-title":"Clin. 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