{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:22:25Z","timestamp":1788909745391,"version":"build-2803163510"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003176","name":"Ministerio de Educaci\u00f3n, Cultura y Deporte","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003176","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007393","name":"Association Fran\u00e7aise contre les Myopathies","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research In","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous <jats:italic>Adck2<\/jats:italic> knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7\u00a0months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either <jats:italic>ad libitum<\/jats:italic> or CR diets for 72\u00a0h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. <jats:italic>In vitro<\/jats:italic> differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle bioenergetics following CR intervention is paralleled with a physical activity improvement, with some increases in two and four limbs strength tests, and weights strength test. Running wheel activity was also partially improved in mutant mice under CR. These results demonstrate that CR intervention, which has been shown to improve age-associated physical and metabolic decline in WT mice, also recovers the defective aerobic metabolism and differentiation of skeletal muscle in mice caused by ADCK2 haploinsufficiency.<\/jats:p>","DOI":"10.3389\/fphys.2022.898792","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T05:06:55Z","timestamp":1657775215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Calorie Restriction Rescues Mitochondrial Dysfunction in Adck2-Deficient Skeletal Muscle"],"prefix":"10.3389","volume":"13","author":[{"given":"Juan Diego","family":"Hern\u00e1ndez-Camacho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J. M.","family":"Fern\u00e1ndez-Ayala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Vicente-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Navas-Enamorado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"L\u00f3pez-Lluch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Oliva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Artuch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Garcia-Villoria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Ribes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"de Cabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime J.","family":"Carvajal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pl\u00e1cido","family":"Navas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"51303","DOI":"10.3791\/51303","article-title":"Assessing Functional Performance in the Mdx Mouse Model","volume":"85","author":"Aartsma-Rus","year":"2014","journal-title":"J. Vis. Exp."},{"key":"B2","doi-asserted-by":"publisher","first-page":"111362","DOI":"10.1016\/j.mad.2020.111362","article-title":"Calorie Restriction Changes Muscle Satellite Cell Proliferation in a Manner Independent of Metabolic Modulation","volume":"192","author":"Abreu","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1042\/EBC20170107","article-title":"Clinical Syndromes Associated with Coenzyme Q10 Deficiency","volume":"62","author":"Alc\u00e1zar-Fabra","year":"2018","journal-title":"Essays Biochem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.freeradbiomed.2021.02.046","article-title":"Primary Coenzyme Q Deficiencies: A Literature Review and Online Platform of Clinical Features to Uncover Genotype-Phenotype Correlations","volume":"167","author":"Alc\u00e1zar-Fabra","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"C26","DOI":"10.1152\/ajpcell.00093.2021","article-title":"The Effect of Young and Old Ex Vivo Human Serum on Cellular Protein Synthesis and Growth in an In Vitro Model of Aging","volume":"321","author":"Allen","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B6","first-page":"529","article-title":"Determination of Lactate, Pyruvate, Beta-Hydroxybutyrate and Acetoacetate with a Centrifugal Analyser","volume":"33","author":"Artuch","year":"1995","journal-title":"Eur. J. Clin. Chem. Clin. Biochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"5179","DOI":"10.1172\/JCI69000","article-title":"ADCK4 Mutations Promote Steroid-Resistant Nephrotic Syndrome through CoQ10 Biosynthesis Disruption","volume":"123","author":"Ashraf","year":"2013","journal-title":"J. Clin. Invest."},{"key":"B8","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/J.EBIOM.2017.06.015","article-title":"Aging and Caloric Restriction Research: A Biological Perspective with Translational Potential","volume":"21","author":"Balasubramanian","year":"2017","journal-title":"eBioMedicine"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16164","article-title":"The Mitochondrial Coenzyme Q Junction and Complex III: Biochemistry and Pathophysiology","author":"Banerjee","year":"2021","journal-title":"FEBS J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1093\/HMG\/DDY405","article-title":"Dynamic Transcriptomic Analysis Reveals Suppression of PGC1\u03b1\/ERR\u03b1 Drives Perturbed Myogenesis in Facioscapulohumeral Muscular Dystrophy","volume":"28","author":"Banerji","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.3390\/genes12101590","article-title":"The Genetic Landscape of Mitochondrial Diseases in Spain: A Nationwide Call","volume":"12","author":"Bellusci","year":"2021","journal-title":"Genes"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e35273","DOI":"10.1371\/journal.pone.0035273","article-title":"Rapid Determination of Myosin Heavy Chain Expression in Rat, Mouse, and Human Skeletal Muscle Using Multicolor Immunofluorescence Analysis","volume":"7","author":"Bloemberg","year":"2012","journal-title":"PLoS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s42003-021-01723-z","article-title":"Molecular and Phenotypic Analysis of Rodent Models Reveals Conserved and Species-specific Modulators of Human Sarcopenia","volume":"4","author":"B\u00f6rsch","year":"2021","journal-title":"Commun. Biol."},{"key":"B14","doi-asserted-by":"publisher","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":"B15","doi-asserted-by":"publisher","first-page":"4486","DOI":"10.1210\/JC.2017-01020","article-title":"A Metabolomic Signature of Acute Caloric Restriction","volume":"102","author":"Collet","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B16","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/s0531-5565(03)00055-x","article-title":"An In Vitro Model of Caloric Restriction","volume":"38","author":"De Cabo","year":"2003","journal-title":"Exp. Gerontol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/J.EXGER.2003.12.003","article-title":"Calorie Restriction Attenuates Age-Related Alterations in the Plasma Membrane Antioxidant System in Rat Liver","volume":"39","author":"De Cabo","year":"2004","journal-title":"Exp. Gerontol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/J.CELL.2014.05.031","article-title":"The Search for Antiaging Interventions: From Elixirs to Fasting Regimens","volume":"157","author":"De Cabo","year":"2014","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e2610","DOI":"10.3791\/2610","article-title":"Measuring the Strength of Mice","volume":"76","author":"Deacon","year":"2013","journal-title":"J. Vis. Exp."},{"key":"B20","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1126\/SCIENCE.AAU2095","article-title":"A Time to Fast","volume":"362","author":"Di Francesco","year":"2018","journal-title":"Science"},{"key":"B21","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/B978-0-12-801415-8.00016-3","article-title":"Analysis and Interpretation of Microplate-Based Oxygen Consumption and pH Data","volume":"547","author":"Divakaruni","year":"2014","journal-title":"Methods Enzymol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e54052","DOI":"10.3791\/54052","article-title":"The Treadmill Fatigue Test: A Simple, High-Throughput Assay of Fatigue-like Behavior for the Mouse","volume":"31","author":"Dougherty","year":"2016","journal-title":"J. Vis. Exp."},{"key":"B23","doi-asserted-by":"publisher","first-page":"170","DOI":"10.2337\/db16-0754","article-title":"Insulin Resistance is Associated with Reduced Mitochondrial Oxidative Capacity Measured by 31P-Magnetic Resonance Spectroscopy in Participants without Diabetes from the Baltimore Longitudinal Study of Aging","volume":"66","author":"Fabbri","year":"2017","journal-title":"Diabetes"},{"key":"B24","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1051\/MEDSCI\/20173311012","article-title":"Dysfonctions Mitochondriales et Vieillissement Musculaire-Une Mise a Jour","volume":"33","author":"Faitg","year":"2017","journal-title":"Med. Sci. Paris."},{"key":"B25","doi-asserted-by":"publisher","first-page":"3383","DOI":"10.1080\/10408398.2020.1798350","article-title":"The Effect of Fasting and Energy Restricting Diets on Markers of Glucose and Insulin Controls: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"61","author":"Fatahi","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e32111","DOI":"10.7554\/eLife.32111","article-title":"Mitochondrial CoQ Deficiency is a Common Driver of Mitochondrial Oxidants and Insulin Resistance","volume":"7","author":"Fazakerley","year":"2018","journal-title":"Elife"},{"key":"B27","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/J.BBAMEM.2005.05.010","article-title":"Coenzyme Q Distribution in HL-60 Human Cells Depends on the Endomembrane System","volume":"1713","author":"Fern\u00e1ndez-Ayala","year":"2005","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-33619-0","article-title":"Non-invasive Continuous Real-Time In Vivo Analysis of Microbial Hydrogen Production Shows Adaptation to Fermentable Carbohydrates in Mice","volume":"8","author":"Fern\u00e1ndez-Calleja","year":"2018","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/J.TEM.2011.12.008","article-title":"Linking Mitochondrial Bioenergetics to Insulin Resistance via Redox Biology","volume":"23","author":"Fisher-Wellman","year":"2012","journal-title":"Trends Endocrinol. Metabolism"},{"key":"B30","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1002\/stem.2248","article-title":"Murine Mesenchymal Stem Cell Commitment to Differentiation is Regulated by Mitochondrial Dynamics","volume":"34","author":"Forni","year":"2016","journal-title":"Stem Cells"},{"key":"B31","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1111\/ACEL.12259","article-title":"In Vitro caloric Restriction Induces Protective Genes and Functional Rejuvenation in Senescent SAMP 8 Astrocytes","volume":"14","author":"Garc\u00eda\u2010Matas","year":"2015","journal-title":"Aging Cell"},{"key":"B32","doi-asserted-by":"publisher","first-page":"12313","DOI":"10.1074\/jbc.RA118.006074","article-title":"Extensive Metabolic Remodeling after Limiting Mitochondrial Lipid Burden Is Consistent with an Improved Metabolic Health Profile","volume":"294","author":"Ghosh","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.ab.2013.05.027","article-title":"Stain-Free Total Protein Staining is a Superior Loading Control to \u03b2-actin for Western Blots","volume":"440","author":"Gilda","year":"2013","journal-title":"Anal. Biochem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.cmet.2020.01.015","article-title":"AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control","volume":"31","author":"Gonz\u00e1lez","year":"2020","journal-title":"Cell Metab."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1093\/gerona\/glv070","article-title":"Reconsidering the Role of Mitochondria in Aging","volume":"70","author":"Gonzalez-Freire","year":"2015","journal-title":"Gerona"},{"key":"B36","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.freeradbiomed.2021.01.017","article-title":"Secondary Coenzyme Q Deficiency in Neurological Disorders","volume":"165","author":"Gueguen","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"eabb2490","DOI":"10.1126\/SCISIGNAL.ABB2490","article-title":"Metabolic Adaptation to Calorie Restriction","volume":"13","author":"Guijas","year":"2020","journal-title":"Sci. Signal."},{"key":"B38","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1093\/GERONA\/GLY161","article-title":"The Impact of Aging, Calorie Restriction and Dietary Fat on Autophagy Markers and Mitochondrial Ultrastructure and Dynamics in Mouse Skeletal Muscle","volume":"74","author":"Guti\u00e9rrez-Casado","year":"2019","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"446097","DOI":"10.1101\/2021.05.28.446097","article-title":"Distinct and Additive Effects of Calorie Restriction and Rapamycin in Aging Skeletal Muscle","author":"Ham","year":"2021","journal-title":"bioRxiv"},{"key":"B40","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/J.MOLCEL.2012.10.024","article-title":"Calorie Restriction and SIRT3 Trigger Global Reprogramming of the Mitochondrial Protein Acetylome","volume":"49","author":"Hebert","year":"2013","journal-title":"Mol. Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1089\/REJ.2006.9.219","article-title":"Caloric Restriction Protects Mitochondrial Function with Aging in Skeletal and Cardiac Muscles","volume":"9","author":"Hepple","year":"2006","journal-title":"Rejuvenation Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3390\/antiox10111785","article-title":"Coenzyme Q at the Hinge of Health and Metabolic Diseases","volume":"10","author":"Hern\u00e1ndez-Camacho","year":"2021","journal-title":"Antioxidants"},{"key":"B43","doi-asserted-by":"publisher","first-page":"e63336","DOI":"10.3791\/63336","article-title":"Isolation of Mitochondria from Mouse Skeletal Muscle for Respirometric Assays","volume":"180","author":"Hern\u00e1ndez-Camacho","year":"2022","journal-title":"J. Vis. Exp."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e14418","DOI":"10.15252\/EMMM.202114418","article-title":"The Ups and Downs of Caloric Restriction and Fasting: from Molecular Effects to Clinical Application","volume":"14","author":"Hofer","year":"2022","journal-title":"EMBO Mol. Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"19908","DOI":"10.1073\/PNAS.0608008103","article-title":"Calorie Restriction Up-Regulates the Plasma Membrane Redox System in Brain Cells and Suppresses Oxidative Stress during Aging","volume":"103","author":"Hyun","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B46","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/J.ARR.2017.05.008","article-title":"Calorie Restriction in Rodents: Caveats to Consider","volume":"39","author":"Ingram","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/j.exger.2004.04.007","article-title":"Effect of Age and Caloric Restriction on Coenzyme Q and \u03b1-tocopherol Levels in the Rat","volume":"39","author":"Kamzalov","year":"2004","journal-title":"Exp. Gerontol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ceb.2017.11.003","article-title":"Mitochondrial Activity in the Regulation of Stem Cell Self-Renewal and Differentiation","volume":"49","author":"Khacho","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1242\/jeb.098863","article-title":"Skeletal Muscle Fuel Selection Occurs at the Mitochondrial Level","volume":"217","author":"Kuzmiak-Glancy","year":"2014","journal-title":"J. Exp. Biol."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2021-107729","article-title":"Human COQ4 Deficiency: Delineating the Clinical, Metabolic and Neuroimaging Phenotypes","author":"Laugwitz","year":"2021","journal-title":"J. Med. Genet."},{"key":"B51","doi-asserted-by":"publisher","first-page":"108944","DOI":"10.1016\/J.JNUTBIO.2022.108944","article-title":"Early-onset Dietary Restriction Maintains Mitochondrial Health, Autophagy and ER Function in the Left Ventricle during Aging","volume":"101","author":"Li","year":"2022","journal-title":"J. Nutr. Biochem."},{"key":"B52","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/J.CMET.2013.03.002","article-title":"Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure","volume":"17","author":"Liesa","year":"2013","journal-title":"Cell Metab."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1113\/JP270543","article-title":"Calorie Restriction as an Intervention in Ageing","volume":"594","author":"L\u00f3pez-Lluch","year":"2016","journal-title":"J. Physiol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/S11357-005-2726-3","article-title":"Mouse Liver Plasma Membrane Redox System Activity is Altered by Aging and Modulated by Calorie Restriction","volume":"27","author":"L\u00f3pez-Lluch","year":"2005","journal-title":"AGE"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1073\/PNAS.0510452103","article-title":"Calorie Restriction Induces Mitochondrial Biogenesis and Bioenergetic Efficiency","volume":"103","author":"L\u00f3pez-Lluch","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The Hallmarks of Aging","volume":"153","author":"L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"Cell"},{"key":"B57","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/J.CELL.2016.07.031","article-title":"Metabolic Control of Longevity","volume":"166","author":"L\u00f3pez-Ot\u00edn","year":"2016","journal-title":"Cell"},{"key":"B58","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/S43587-020-00013-3","article-title":"Intermittent and Periodic Fasting, Longevity and Disease","volume":"1","author":"Longo","year":"2021","journal-title":"Nat. Aging"},{"key":"B59","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1172\/JCI73946","article-title":"Essential Role for Autophagy in Life Span Extension","volume":"125","author":"Madeo","year":"2015","journal-title":"J. Clin. Invest."},{"key":"B60","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1089\/ARS.2012.4866","article-title":"Mitochondrial Metabolic Reprogramming Induced by Calorie Restriction","volume":"19","author":"Martin-Montalvo","year":"2013","journal-title":"Antioxidants Redox Signal."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-019-13694-1","article-title":"Mitochondrial Oxidative Capacity and NAD+ Biosynthesis are Reduced in Human Sarcopenia across Ethnicities","volume":"10","author":"Migliavacca","year":"2019","journal-title":"Nat. Commun."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1016\/J.CMET.2016.05.027","article-title":"Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice","volume":"23","author":"Mitchell","year":"2016","journal-title":"Cell Metab."},{"key":"B63","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/J.CMET.2018.02.001","article-title":"Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice","volume":"27","author":"Mitchell","year":"2018","journal-title":"Cell Metab."},{"key":"B64","doi-asserted-by":"publisher","first-page":"111519","DOI":"10.1016\/j.exger.2021.111519","article-title":"Prolonged Caloric Restriction Ameliorates Age-Related Atrophy in Slow and Fast Muscle Fibers of Rat Soleus Muscle","volume":"154","author":"Mizunoe","year":"2021","journal-title":"Exp. Gerontol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1530\/EC-14-0092","article-title":"Mitochondrial Dysfunction and Insulin Resistance: An Update","volume":"4","author":"Montgomery","year":"2015","journal-title":"Endocr. Connect."},{"key":"B66","doi-asserted-by":"publisher","first-page":"110875","DOI":"10.1016\/J.EXGER.2020.110875","article-title":"Impact of Calorie Restriction on Energy Metabolism in Humans","volume":"133","author":"Most","year":"2020","journal-title":"Exp. Gerontol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/978-1-4939-1435-7_6","article-title":"Isolation, Culture and Immunostaining of Skeletal Muscle Fibres to Study Myogenic Progression in Satellite Cells","volume":"1210","author":"Moyle","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1016\/J.CELL.2014.11.034","article-title":"Metabolic Inflexibility: When Mitochondrial Indecision Leads to Metabolic Gridlock","volume":"159","author":"Muoio","year":"2014","journal-title":"Cell"},{"key":"B69","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.jpeds.2020.08.025","article-title":"Clinical Presentation, Genetic Etiology, and Coenzyme Q10 Levels in 55 Children with Combined Enzyme Deficiencies of the Mitochondrial Respiratory Chain","volume":"228","author":"Naess","year":"2021","journal-title":"J. Pediatr."},{"key":"B70","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1002\/BIOF.1733","article-title":"Secondary CoQ10 Deficiency, Bioenergetics Unbalance in Disease and Aging","volume":"47","author":"Navas","year":"2021","journal-title":"BioFactors"},{"key":"B71","doi-asserted-by":"publisher","first-page":"233","DOI":"10.18632\/aging.100732","article-title":"Caloric Restriction Induces Heat Shock Response and Inhibits B16F10 Cell Tumorigenesis Both In Vitro and In Vivo","volume":"7","author":"Novelle","year":"2015","journal-title":"Aging"},{"key":"B72","doi-asserted-by":"publisher","first-page":"e62952","DOI":"10.7554\/eLife.62952","article-title":"A Cross-Sectional Study of Functional and Metabolic Changes during Aging through the Lifespan in Male Mice","volume":"10","author":"Petr","year":"2021","journal-title":"Elife"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-20760-6","article-title":"Perspectives on Skeletal Muscle Stem Cells","volume":"12","author":"Relaix","year":"2021","journal-title":"Nat. Commun."},{"key":"B74","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1093\/gerona\/glv080","article-title":"Measures of Healthspan as Indices of Aging in Mice-A Recommendation","volume":"71","author":"Richardson","year":"2016","journal-title":"Gerona"},{"key":"B75","doi-asserted-by":"publisher","first-page":"55099","DOI":"10.3791\/55099","article-title":"Activating Autophagy by Aerobic Exercise in Mice","volume":"120","author":"Rocchi","year":"2017","journal-title":"J. Vis. Exp."},{"key":"B76","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3390\/jcm6030027","article-title":"Biochemical Assessment of Coenzyme Q10 Deficiency","volume":"6","author":"Rodr\u00edguez-Aguilera","year":"2017","journal-title":"J. Clin. Med."},{"key":"B77","doi-asserted-by":"publisher","first-page":"e48395","DOI":"10.15252\/EMBR.201948395","article-title":"Causal Roles of Mitochondrial Dynamics in Longevity and Healthy Aging","volume":"20","author":"Sharma","year":"2019","journal-title":"EMBO Rep."},{"key":"B78","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1210\/ER.2017-00211","article-title":"Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease","volume":"39","author":"Smith","year":"2018","journal-title":"Endocr. Rev."},{"key":"B79","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1146\/ANNUREV-PHARMTOX-010716-104908","article-title":"Repairing Mitochondrial Dysfunction in Disease","volume":"58","author":"Sorrentino","year":"2018","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1038\/nprot.2012.058","article-title":"Assessment of Mitochondrial Respiratory Chain Enzymatic Activities on Tissues and Cultured Cells","volume":"7","author":"Spinazzi","year":"2012","journal-title":"Nat. Protoc."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1126\/science.abi7495","article-title":"Fumarate Is a Terminal Electron Acceptor in the Mammalian Electron Transport Chain","volume":"374","author":"Spinelli","year":"2021","journal-title":"Science"},{"key":"B82","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/S40279-014-0154-1\/FIGURES\/2","article-title":"New Insights into the Interaction of Carbohydrate and Fat Metabolism during Exercise","volume":"44","author":"Spriet","year":"2014","journal-title":"Sports Med."},{"key":"B83","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/JCSM.12238","article-title":"Skeletal Muscle Performance and Ageing","volume":"9","author":"Tieland","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"B84","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1002\/ana.25751","article-title":"Clinico\u2010Genetic, Imaging and Molecular Delineation of COQ8A\u2010Ataxia: A Multicenter Study of 59 Patients","volume":"88","author":"Trasch\u00fctz","year":"2020","journal-title":"Ann. Neurol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.3390\/jcm8091374","article-title":"ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency","volume":"8","author":"V\u00e1zquez-Fonseca","year":"2019","journal-title":"J. Clin. Med."},{"key":"B86","doi-asserted-by":"publisher","first-page":"2105587","DOI":"10.1002\/ADVS.202105587","article-title":"Hepatic Suppression of Mitochondrial Complex II Assembly Drives Systemic Metabolic Benefits","volume":"9","author":"Wang","year":"2022","journal-title":"Adv. Sci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.celrep.2019.08.084","article-title":"Calorie-Restriction-Induced Insulin Sensitivity is Mediated by Adipose mTORC2 and Not Required for Lifespan Extension","volume":"29","author":"Yu","year":"2019","journal-title":"Cell Rep."},{"key":"B88","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1111\/ACEL.12568","article-title":"Muscle Strength Mediates the Relationship between Mitochondrial Energetics and Walking Performance","volume":"16","author":"Zane","year":"2017","journal-title":"Aging Cell"},{"key":"B89","doi-asserted-by":"publisher","first-page":"8819","DOI":"10.1074\/jbc.RA118.006790","article-title":"Defective Fatty Acid Oxidation in Mice with Muscle-specific Acyl-CoA Synthetase 1 Deficiency Increases Amino Acid Use and Impairs Muscle Function","volume":"294","author":"Zhao","year":"2019","journal-title":"J. Biol. Chem."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.898792\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T12:59:19Z","timestamp":1658408359000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.898792\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":89,"alternative-id":["10.3389\/fphys.2022.898792"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.898792","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,14]]},"article-number":"898792"}}