{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:26:49Z","timestamp":1791556009127,"version":"4.3.4"},"reference-count":43,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T00:00:00Z","timestamp":1492560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Metabolism"],"published-print":{"date-parts":[[2017,6]]},"DOI":"10.1016\/j.cmet.2017.04.021","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T14:01:44Z","timestamp":1495720904000},"page":"1374-1389.e6","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":561,"title":["Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence"],"prefix":"10.1016","volume":"25","author":[{"given":"Caterina","family":"Tezze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanina","family":"Romanello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Andrea","family":"Desbats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Paolo","family":"Fadini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Albiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Favaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Ciciliot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eugenia","family":"Soriano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Morbidoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Cerqua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Loefler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Kern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Franceschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Salvioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Conte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Blaauw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Zampieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Salviati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Scorrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Sandri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cmet.2017.04.021_bib1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/79944","article-title":"OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28","volume":"26","author":"Alexander","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cmet.2017.04.021_bib2","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1093\/brain\/awm298","article-title":"OPA1 mutations induce mitochondrial DNA instability and optic atrophy \u2018plus\u2019 phenotypes","volume":"131","author":"Amati-Bonneau","year":"2008","journal-title":"Brain"},{"key":"10.1016\/j.cmet.2017.04.021_bib3","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cmet.2014.12.021","article-title":"Muscle as a \u201cmediator\u201d of systemic metabolism","volume":"21","author":"Baskin","year":"2015","journal-title":"Cell Metab."},{"key":"10.1016\/j.cmet.2017.04.021_bib4","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1096\/fj.09-131870","article-title":"Inducible activation of Akt increases skeletal muscle mass and force without satellite cell activation","volume":"23","author":"Blaauw","year":"2009","journal-title":"FASEB J"},{"key":"10.1016\/j.cmet.2017.04.021_bib5","doi-asserted-by":"crossref","first-page":"6017","DOI":"10.1113\/jphysiol.2013.263079","article-title":"Altered skeletal muscle mitochondrial biogenesis but improved endurance capacity in trained OPA1-deficient mice","volume":"591","author":"Caffin","year":"2013","journal-title":"J.\u00a0Physiol."},{"key":"10.1016\/j.cmet.2017.04.021_bib6","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1083\/jcb.200211046","article-title":"Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development","volume":"160","author":"Chen","year":"2003","journal-title":"J.\u00a0Cell Biol."},{"key":"10.1016\/j.cmet.2017.04.021_bib7","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.cell.2010.02.026","article-title":"Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations","volume":"141","author":"Chen","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.cmet.2017.04.021_bib8","doi-asserted-by":"crossref","first-page":"33953","DOI":"10.1038\/srep33953","article-title":"Circulating Fibroblast Growth Factor 21 is Associated with Diastolic Dysfunction in Heart Failure Patients with Preserved Ejection Fraction","volume":"6","author":"Chou","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.cmet.2017.04.021_bib9","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.cell.2006.06.021","article-title":"Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling","volume":"126","author":"Cipolat","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.cmet.2017.04.021_bib10","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.cell.2013.08.032","article-title":"Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency","volume":"155","author":"Cogliati","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.cmet.2017.04.021_bib11","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1093\/hmg\/ddm079","article-title":"Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function","volume":"16","author":"Davies","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.cmet.2017.04.021_bib12","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/79936","article-title":"Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy","volume":"26","author":"Delettre","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cmet.2017.04.021_bib13","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cell.2010.10.007","article-title":"FOXO\/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging","volume":"143","author":"Demontis","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.cmet.2017.04.021_bib14","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/acel.12126","article-title":"The influence of skeletal muscle on systemic aging and lifespan","volume":"12","author":"Demontis","year":"2013","journal-title":"Aging Cell"},{"key":"10.1016\/j.cmet.2017.04.021_bib15","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.celrep.2014.05.001","article-title":"Intertissue control of the nucleolus via a myokine-dependent longevity pathway","volume":"7","author":"Demontis","year":"2014","journal-title":"Cell Rep."},{"key":"10.1016\/j.cmet.2017.04.021_bib16","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cell.2006.06.025","article-title":"OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion","volume":"126","author":"Frezza","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.cmet.2017.04.021_bib17","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nprot.2006.478","article-title":"Organelle isolation: functional mitochondria from mouse liver, muscle and cultured fibroblasts","volume":"2","author":"Frezza","year":"2007","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.cmet.2017.04.021_bib18","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1096\/fj.10-168799","article-title":"Novel insights into the regulation of skeletal muscle protein synthesis as revealed by a new nonradioactive in\u00a0vivo technique","volume":"25","author":"Goodman","year":"2011","journal-title":"FASEB J."},{"key":"10.1016\/j.cmet.2017.04.021_bib19","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1038\/nm.2247","article-title":"Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration","volume":"16","author":"Grumati","year":"2010","journal-title":"Nat. Med."},{"key":"10.1016\/j.cmet.2017.04.021_bib20","first-page":"77","article-title":"Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals","volume":"2","author":"Hanks","year":"2015","journal-title":"J.\u00a0Clin. Transl. Endocrinol."},{"key":"10.1016\/j.cmet.2017.04.021_bib21","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":"10.1016\/j.cmet.2017.04.021_bib22","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":"10.1016\/j.cmet.2017.04.021_bib23","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1212\/WNL.0000000000003374","article-title":"FGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders","volume":"87","author":"Lehtonen","year":"2016","journal-title":"Neurology"},{"key":"10.1016\/j.cmet.2017.04.021_bib24","doi-asserted-by":"crossref","first-page":"4886","DOI":"10.1210\/jc.2016-2308","article-title":"Association Between Serum Fibroblast Growth Factor 21 and Mortality Among Patients With Coronary Artery Disease","volume":"101","author":"Li","year":"2016","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.cmet.2017.04.021_bib25","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.4161\/auto.32154","article-title":"Autophagy is not required to sustain exercise and PRKAA1\/AMPK activity but is important to prevent mitochondrial damage during physical activity","volume":"10","author":"Lo Verso","year":"2014","journal-title":"Autophagy"},{"key":"10.1016\/j.cmet.2017.04.021_bib26","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.cmet.2007.11.001","article-title":"FoxO3 controls autophagy in skeletal muscle in\u00a0vivo","volume":"6","author":"Mammucari","year":"2007","journal-title":"Cell Metab."},{"key":"10.1016\/j.cmet.2017.04.021_bib27","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.cmet.2009.10.008","article-title":"Autophagy is required to maintain muscle mass","volume":"10","author":"Masiero","year":"2009","journal-title":"Cell Metab."},{"key":"10.1016\/j.cmet.2017.04.021_bib28","doi-asserted-by":"crossref","first-page":"6670","DOI":"10.1038\/ncomms7670","article-title":"Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy","volume":"6","author":"Milan","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cmet.2017.04.021_bib29","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.cmet.2015.05.011","article-title":"Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits","volume":"22","author":"Neufer","year":"2015","journal-title":"Cell Metab."},{"key":"10.1016\/j.cmet.2017.04.021_bib30","doi-asserted-by":"crossref","first-page":"422","DOI":"10.3389\/fphys.2015.00422","article-title":"Mitochondrial Quality Control and Muscle Mass Maintenance","volume":"6","author":"Romanello","year":"2016","journal-title":"Front. Physiol."},{"key":"10.1016\/j.cmet.2017.04.021_bib31","doi-asserted-by":"crossref","first-page":"85","DOI":"10.4081\/bam.2013.3.85","article-title":"Strength training in elderly people improves static balance: a randomized controlled trial","volume":"23","author":"\u0160arabon","year":"2013","journal-title":"Eur. J. Transl. Myol."},{"key":"10.1016\/j.cmet.2017.04.021_bib32","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1055\/s-0032-1331190","article-title":"Reliability of maximal voluntary contraction related parameters measured by a portable isometric knee dynamometer","volume":"23","author":"\u0160arabon","year":"2013","journal-title":"Phys. Med. Rehabil. Kuror."},{"key":"10.1016\/j.cmet.2017.04.021_bib33","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ymgme.2011.04.018","article-title":"Early-onset severe neuromuscular phenotype associated with compound heterozygosity for OPA1 mutations","volume":"103","author":"Schaaf","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.cmet.2017.04.021_bib34","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.1111\/febs.12253","article-title":"Mechanisms regulating skeletal muscle growth and atrophy","volume":"280","author":"Schiaffino","year":"2013","journal-title":"FEBS J."},{"key":"10.1016\/j.cmet.2017.04.021_bib35","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nmeth.1314","article-title":"SUnSET, a nonradioactive method to monitor protein synthesis","volume":"6","author":"Schmidt","year":"2009","journal-title":"Nat. Methods"},{"key":"10.1016\/j.cmet.2017.04.021_bib36","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1136\/jmedgenet-2015-103361","article-title":"Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation","volume":"53","author":"Spiegel","year":"2016","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.cmet.2017.04.021_bib37","doi-asserted-by":"crossref","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":"10.1016\/j.cmet.2017.04.021_bib38","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/S1474-4422(11)70155-7","article-title":"FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study","volume":"10","author":"Suomalainen","year":"2011","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.cmet.2017.04.021_bib39","doi-asserted-by":"crossref","first-page":"aad0116","DOI":"10.1126\/science.aad0116","article-title":"Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice","volume":"350","author":"Wai","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.cmet.2017.04.021_bib40","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1126\/science.aac4357","article-title":"Mitochondrial dysfunction and longevity in animals: Untangling the knot","volume":"350","author":"Wang","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.cmet.2017.04.021_bib41","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/gerona\/glu006","article-title":"Lifelong physical exercise delays age-associated skeletal muscle decline","volume":"70","author":"Zampieri","year":"2015","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.cmet.2017.04.021_bib42","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.cmet.2007.11.004","article-title":"FoxO3 coordinately activates protein degradation by the autophagic\/lysosomal and proteasomal pathways in atrophying muscle cells","volume":"6","author":"Zhao","year":"2007","journal-title":"Cell Metab."},{"key":"10.1016\/j.cmet.2017.04.021_bib43","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/ng1341","article-title":"Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A","volume":"36","author":"Z\u00fcchner","year":"2004","journal-title":"Nat. Genet."}],"container-title":["Cell Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1550413117302279?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1550413117302279?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T08:50:39Z","timestamp":1535791839000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1550413117302279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["S1550413117302279"],"URL":"https:\/\/doi.org\/10.1016\/j.cmet.2017.04.021","relation":{},"ISSN":["1550-4131"],"issn-type":[{"value":"1550-4131","type":"print"}],"subject":[],"published":{"date-parts":[[2017,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence","name":"articletitle","label":"Article Title"},{"value":"Cell Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cmet.2017.04.021","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}