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The decline of skeletal muscle performance is characterized by bioenergetic impairment and severe oxidative stress, and does not always strictly correlate with muscle mass loss. We chose to investigate the ability of the metabolic modulator Ranolazine to counteract skeletal muscle dysfunctions that occur with aging. For this purpose, we treated aged C57BL\/6 mice with Ranolazine\/vehicle for 14 days and collected the tibialis anterior and gastrocnemius muscles for histological and gene expression analyses, respectively. We found that Ranolazine treatment significantly increased the muscle strength of aged mice. At the histological level, we found an increase in centrally nucleated fibers associated with an up-regulation of genes encoding MyoD, Periostin and Osteopontin, thus suggesting a remodeling of the muscle even in the absence of physical exercise. Notably, these beneficial effects of Ranolazine were also accompanied by an up-regulation of antioxidant and mitochondrial genes as well as of NADH-dehydrogenase activity, together with a more efficient protection from oxidative damage in the skeletal muscle. These data indicate that the protection of muscle from oxidative stress by Ranolazine might represent a valuable approach to increase skeletal muscle strength in elderly populations.<\/jats:p>","DOI":"10.3390\/metabo12070663","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T11:32:23Z","timestamp":1658143943000},"page":"663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ranolazine Counteracts Strength Impairment and Oxidative Stress in Aged Sarcopenic Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9436-8783","authenticated-orcid":false,"given":"Alessio","family":"Torcinaro","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), Via Ercole Ramarini, 32, Monterotondo, 00015 Rome, Italy"},{"name":"Istituto Dermopatico dell\u2019Immacolata (IDI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Experimental Immunology Laboratory, Via Monti di Creta, 104, 00167 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donato","family":"Cappetta","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Division of Pharmacology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0034-5450","authenticated-orcid":false,"given":"Francesca","family":"De Santa","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), Via Ercole Ramarini, 32, Monterotondo, 00015 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marialucia","family":"Telesca","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Division of Pharmacology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7818-2209","authenticated-orcid":false,"given":"Massimiliano","family":"Leigheb","sequence":"additional","affiliation":[{"name":"Orthopaedics and Traumatology Unit, \u201cMaggiore della Carit\u00e0\u201d Hospital, Department of Health Sciences, University of Piemonte Orientale (UPO), 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liberato","family":"Berrino","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Division of Pharmacology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konrad","family":"Urbanek","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80138 Naples, Italy"},{"name":"CEINGE-Advanced Biotechnologies, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Division of Pharmacology, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9596-4624","authenticated-orcid":false,"given":"Elisabetta","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The Hallmarks of Aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.bone.2017.09.008","article-title":"A review of sarcopenia: Enhancing awareness of an increasingly prevalent disease","volume":"105","author":"Marty","year":"2017","journal-title":"Bone"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1093\/ageing\/afz046","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/emmm.200900045","article-title":"Molecular aging and rejuvenation of human muscle stem cells","volume":"1","author":"Carlson","year":"2009","journal-title":"EMBO Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1089\/ars.2020.8071","article-title":"From Development to Aging: The Path to Cellular Senescence","volume":"34","author":"Sacco","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1089\/ars.2017.7420","article-title":"The Role of Metabolic Remodeling in Macrophage Polarization and Its Effect on Skeletal Muscle Regeneration","volume":"30","author":"Vitiello","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1016\/j.biocel.2013.06.024","article-title":"Mitochondrial dysfunction and sarcopenia of aging: From signaling pathways to clinical trials","volume":"45","author":"Marzetti","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.tem.2012.12.003","article-title":"Skeletal muscle aging and the mitochondrion","volume":"24","author":"Johnson","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/gerona\/gls196","article-title":"Skeletal muscle mitochondrial energetics are associated with maximal aerobic capacity and walking speed in older adults","volume":"68","author":"Coen","year":"2012","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5618","DOI":"10.1073\/pnas.0501559102","article-title":"Decline in skeletal muscle mitochondrial function with aging in humans","volume":"102","author":"Short","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1111\/j.1474-9726.2012.00844.x","article-title":"The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high- and low-functioning elderly individuals","volume":"11","author":"Joseph","year":"2012","journal-title":"Aging Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1128\/MCB.01036-12","article-title":"Genomic and proteomic profiling reveals reduced mitochondrial function and disruption of the neuromuscular junction driving rat sarcopenia","volume":"33","author":"Ibebunjo","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"ref_13","first-page":"40","article-title":"Muscle fibre type adaptation in the elderly human muscle. Scand","volume":"13","author":"Andersen","year":"2003","journal-title":"J. Med. Sci. Sports"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1016\/j.biocel.2013.05.016","article-title":"Muscle type and fiber type specificity in muscle wasting","volume":"45","author":"Ciciliot","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/MCO.0b013e328360272d","article-title":"Mechanisms for fiber-type specificity of skeletal muscle atrophy","volume":"16","author":"Wang","year":"2013","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3389\/fmed.2019.00184","article-title":"The Biological Foundations of Sarcopenia: Established and Promising Markers","volume":"6","author":"Casati","year":"2019","journal-title":"Front. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1089\/ars.2013.5773","article-title":"Exercise-Induced Skeletal Muscle Remodeling and Metabolic Adaptation: Redox Signaling and Role of Autophagy","volume":"21","author":"Ferraro","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4617801","DOI":"10.1155\/2019\/4617801","article-title":"Changes in Redox Signaling in the Skeletal Muscle with Aging","volume":"2019","author":"Szentesi","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1515\/hsz-2012-0247","article-title":"Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy","volume":"394","author":"Calvani","year":"2013","journal-title":"Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1016\/j.addr.2009.06.006","article-title":"Mitochondrial biogenesis in exercise and in ageing","volume":"61","author":"Borras","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/S0306-3623(97)00301-7","article-title":"Ranolazine: A Novel Metabolic Modulator for the Treatment of Angina","volume":"30","author":"McCormack","year":"1998","journal-title":"Gen. Pharmacol. Vasc. Syst."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S1388-9842(01)00183-0","article-title":"Partial fatty acid oxidation inhibitors: A potentially new class of drugs for heart failure","volume":"4","author":"Sabbaha","year":"2002","journal-title":"Eur. J. Hear. Fail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1124\/jpet.112.198887","article-title":"A novel, potent, and selective inhibitor of cardiac late sodium current suppresses experimental arrhythmias","volume":"344","author":"Belardinelli","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2174\/157489007779606095","article-title":"Ranolazine, a partial fatty acid oxidation inhibitor, its potential benefit in angina and other cardiovascular disorders","volume":"2","author":"Bhandari","year":"2007","journal-title":"Recent Patents Cardiovasc. Drug Discov."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e003196","DOI":"10.1161\/JAHA.116.003196","article-title":"Ranolazine: A Contemporary Review","volume":"5","author":"Sedlak","year":"2016","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0014-2999(01)00920-7","article-title":"Ranolazine, a partial fatty acid oxidation inhibitor, reduces myocardial infarct size and cardiac troponin T release in the rat","volume":"418","author":"Zacharowski","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5094","DOI":"10.1111\/febs.12484","article-title":"The metabolic modulator trimetazidine triggers autophagy and counteracts stress-induced atrophy in skeletal muscle myotubes","volume":"280","author":"Ferraro","year":"2013","journal-title":"FEBS J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/jcsm.12097","article-title":"Improvement of skeletal muscle performance in ageing by the metabolic modulator Trimetazidine","volume":"7","author":"Ferraro","year":"2016","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.phrs.2011.01.003","article-title":"Trimetazidine improves exercise performance in patients with peripheral arterial disease","volume":"63","author":"Vitale","year":"2011","journal-title":"Pharmacol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1002\/jcsm.12226","article-title":"The mitochondrial metabolic reprogramming agent trimetazidine as an \u2018exercise mimetic\u2019 in cachectic C26-bearing mice","volume":"8","author":"Molinari","year":"2017","journal-title":"J. Cachex- Sarcopenia Muscle"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Deacon, R.M. (2013). Measuring the strength of mice. J. Vis. Exp., e2610.","DOI":"10.3791\/2610"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13939","DOI":"10.18632\/aging.103802","article-title":"Both ghrelin deletion and unacylated ghrelin overexpression preserve muscles in aging mice","volume":"12","author":"Agosti","year":"2020","journal-title":"Aging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1152\/japplphysiol.00351.2014","article-title":"Identification of a conserved set of upregulated genes in mouse skeletal muscle hypertrophy and regrowth","volume":"118","author":"Chaillou","year":"2015","journal-title":"J. Appl. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yamakawa, H., Kusumoto, D., Hashimoto, H., and Yuasa, S. (2020). Stem Cell Aging in Skeletal Muscle Regeneration and Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051830"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s12020-016-1181-5","article-title":"Ranolazine promotes muscle differentiation and reduces oxidative stress in C2C12 skeletal muscle cells","volume":"58","author":"Ileana","year":"2016","journal-title":"Endocrine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.stem.2012.04.002","article-title":"Short-term calorie restriction enhances skeletal muscle stem cell function","volume":"10","author":"Cerletti","year":"2012","journal-title":"Cell Stem Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1111\/febs.12189","article-title":"Metabolic reprogramming as a novel regulator of skeletal muscle development and regeneration","volume":"280","author":"Ryall","year":"2013","journal-title":"FEBS J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"897","DOI":"10.3389\/fphys.2019.00897","article-title":"Metabolic Reprogramming Promotes Myogenesis During Aging","volume":"10","author":"Belli","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.stem.2014.12.004","article-title":"The NAD(+)-dependent SIRT1 deacetylase translates a metabolic switch into regulatory epigenetics in skeletal muscle stem cells","volume":"16","author":"Ryall","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/1471-2318-13-104","article-title":"Elevated hydrogen peroxide and decreased catalase and glutathione peroxidase protection are associated with aging sarcopenia","volume":"13","author":"Lewandowski","year":"2013","journal-title":"BMC Geriatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"ii1","DOI":"10.1093\/annonc\/mdx810","article-title":"Sarcopenic obesity: Hidden muscle wasting and its impact for survival and complications of cancer therapy","volume":"29","author":"Baracos","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bmb\/ldq008","article-title":"Sarcopenia: Characteristics, mechanisms and functional significance","volume":"95","author":"Narici","year":"2010","journal-title":"Br. Med. Bull."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1111\/bph.13791","article-title":"Effects of ranolazine in a model of doxorubicin-induced left ventricle diastolic dysfunction","volume":"174","author":"Cappetta","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ijcard.2016.04.168","article-title":"Long-term administration of ranolazine attenuates diastolic dysfunction and adverse myocardial remodeling in a model of heart failure with preserved ejection fraction","volume":"217","author":"Cappetta","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/ejhf.50","article-title":"Ranolazine protects from doxorubicin-induced oxidative stress and cardiac dysfunction","volume":"16","author":"Tocchetti","year":"2014","journal-title":"Eur. J. Heart Fail."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.lfs.2016.05.026","article-title":"Ranolazine improves oxidative stress and mitochondrial function in the atrium of acetylcholine-CaCl2 induced atrial fibrillation rats","volume":"156","author":"Zou","year":"2016","journal-title":"Life Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8912768","DOI":"10.1155\/2019\/8912768","article-title":"Dipeptidyl Peptidase 4 Inhibition Ameliorates Chronic Kidney Disease in a Model of Salt-Dependent Hypertension","volume":"2019","author":"Cappetta","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1532-5415.1972.tb00787.x","article-title":"The Biologic Clock: The Mitochondria?","volume":"20","author":"Harman","year":"1972","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/0531-5565(80)90010-8","article-title":"Mitochondrial role in cell aging","volume":"15","author":"Miquel","year":"1980","journal-title":"Exp. Gerontol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.arr.2006.03.002","article-title":"Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle","volume":"5","author":"Dirks","year":"2006","journal-title":"Ageing Res. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/sj.emboj.7601963","article-title":"Fission and selective fusion govern mitochondrial segregation and elimination by autophagy","volume":"27","author":"Twig","year":"2008","journal-title":"EMBO J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101087","DOI":"10.1016\/j.isci.2020.101087","article-title":"Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1G93A Mice Predates Disease Onset and Is A Promising Therapeutic Target","volume":"23","author":"Scaricamazza","year":"2020","journal-title":"iScience"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.nbd.2005.06.010","article-title":"Apaf1 mediates apoptosis and mitochondrial damage induced by mutant human SOD1s typical of familial amyotrophic lateral sclerosis","volume":"21","author":"Cozzolino","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.exger.2003.09.012","article-title":"The contribution of reactive oxygen species to sarcopenia and muscle ageing","volume":"39","author":"Fulle","year":"2003","journal-title":"Exp. Gerontol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.exger.2010.03.007","article-title":"Remodeling of the neuromuscular junction precedes sarcopenia related alterations in myofibers","volume":"45","author":"Deschenes","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1096\/fj.09-146308","article-title":"Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration","volume":"24","author":"Jang","year":"2009","journal-title":"FASEB J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"469","DOI":"10.2165\/00003088-200645050-00003","article-title":"Clinical Pharmacokinetics of Ranolazine","volume":"45","author":"Jerling","year":"2006","journal-title":"Clin. Pharmacokinet."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Madaro, L., Torcinaro, A., De Bardi, M., Contino, F.F., Pelizzola, M., Diaferia, G.R., Imeneo, G., Bouch\u00e9, M., Puri, P.L., and De Santa, F. (2019). Macrophages Fine Tune Satellite Cell Fate in Dystrophic Skeletal Muscle of Mdx Mice. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1008408"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Laghi, V., Ricci, V., De Santa, F., and Torcinaro, A. (2022). A User-Friendly Approach for Routine Histopathological and Morphometric Analysis of Skeletal Muscle Using CellProfiler Software. Diagnostics, 12.","DOI":"10.3390\/diagnostics12030561"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10974-005-9014-9","article-title":"TGF-\u03b21 favors the development of fast type identity during soleus muscle regeneration","volume":"27","author":"Noirez","year":"2005","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13395-020-00237-2","article-title":"Exercise promotes satellite cell contribution to myofibers in a load-dependent manner","volume":"10","author":"Masschelein","year":"2020","journal-title":"Skelet. Muscle"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1089\/ars.2016.6643","article-title":"Oxidative Stress-Induced miR-200c Disrupts the Regulatory Loop Among SIRT1, FOXO1, and eNOS","volume":"27","author":"Carlomosti","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_63","first-page":"1732","article-title":"Repurposing of Trimetazidine for amyotrophic lateral sclerosis: A study in SOD1G93A mice","volume":"179","author":"Scaricamazza","year":"2021","journal-title":"J. Cereb. Blood Flow Metab."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/7\/663\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:53:13Z","timestamp":1760140393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/7\/663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,18]]},"references-count":63,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["metabo12070663"],"URL":"https:\/\/doi.org\/10.3390\/metabo12070663","relation":{},"ISSN":["2218-1989"],"issn-type":[{"type":"electronic","value":"2218-1989"}],"subject":[],"published":{"date-parts":[[2022,7,18]]}}}