{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T01:23:01Z","timestamp":1778548981060,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T00:00:00Z","timestamp":1545004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015822","name":"Fondazione Roma","doi-asserted-by":"publisher","award":["NCDs Call for Proposals 2013"],"award-info":[{"award-number":["NCDs Call for Proposals 2013"]}],"id":[{"id":"10.13039\/501100015822","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["IMI-JU #115621"],"award-info":[{"award-number":["IMI-JU #115621"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"publisher","award":["D3.2 2013"],"award-info":[{"award-number":["D3.2 2013"]}],"id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"publisher","award":["D3.2 2015"],"award-info":[{"award-number":["D3.2 2015"]}],"id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro Studi Achille e Linda Lorenzon","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100005362","name":"Universita degli Studi di Bari Aldo Moro","doi-asserted-by":"publisher","award":["Progetti di Ateneo 2012"],"award-info":[{"award-number":["Progetti di Ateneo 2012"]}],"id":[{"id":"10.13039\/501100005362","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Istituto Banco di Napoli-Fondazione 2015","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG17994"],"award-info":[{"award-number":["R01AG17994"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Mitochondrial dysfunction is a relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at a non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the hearts of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n = 8) or placebo (n = 8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and the abundance of mtDNA4834 deletion), and the mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. The binding of mitochondrial transcription factor A to mtDNA regions involved in replication and deletion generation was enhanced following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling were found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.<\/jats:p>","DOI":"10.3390\/biom8040177","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T03:12:30Z","timestamp":1545102750000},"page":"177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Administration of Enalapril Started Late in Life Attenuates Hypertrophy and Oxidative Stress Burden, Increases Mitochondrial Mass, and Modulates Mitochondrial Quality Control Signaling in the Rat Heart"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-3487","authenticated-orcid":false,"given":"Anna","family":"Picca","sequence":"first","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCSS, Universit\u00e0 Cattolica del Sacro Cuore, L.go A. Gemelli 1, 00168 Rome, Italy"},{"name":"Institute of Internal Medicine and Geriatrics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7005-8708","authenticated-orcid":false,"given":"Giuseppe","family":"Sirago","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vito","family":"Pesce","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela Maria Serena","family":"Lezza","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5472-2365","authenticated-orcid":false,"given":"Riccardo","family":"Calvani","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCSS, Universit\u00e0 Cattolica del Sacro Cuore, L.go A. Gemelli 1, 00168 Rome, Italy"},{"name":"Institute of Internal Medicine and Geriatrics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Bossola","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCSS, Universit\u00e0 Cattolica del Sacro Cuore, L.go A. Gemelli 1, 00168 Rome, Italy"},{"name":"Institute of Surgical Sciences, Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCSS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele Rocco","family":"Villani","sequence":"additional","affiliation":[{"name":"Institute of Internal Medicine and Geriatrics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Landi","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCSS, Universit\u00e0 Cattolica del Sacro Cuore, L.go A. Gemelli 1, 00168 Rome, Italy"},{"name":"Institute of Internal Medicine and Geriatrics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiaan","family":"Leeuwenburgh","sequence":"additional","affiliation":[{"name":"Department of Aging and Geriatric Research, Institute on Aging, Division of Biology of Aging, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Bernabei","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCSS, Universit\u00e0 Cattolica del Sacro Cuore, L.go A. 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