{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:48:44Z","timestamp":1790704124942,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T00:00:00Z","timestamp":1501459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01\u2010CA111365"],"award-info":[{"award-number":["2R01\u2010CA111365"]}],"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":["CA169046"],"award-info":[{"award-number":["CA169046"]}],"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 CA086862"],"award-info":[{"award-number":["P30 CA086862"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011343","name":"Holden Comprehensive Cancer Center, University of Iowa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011343","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2017,10]]},"abstract":"Summary<\/jats:title>\n \n Replicative and chronological lifespan are two different modes of cellular aging. Chronological lifespan is defined as the duration during which quiescent normal cells retain their capacity to re\u2010enter the proliferative cycle. This study investigated whether changes in metabolism occur during aging of quiescent normal human fibroblasts (\n NHF<\/jats:styled-content>\n s) and the mechanisms that regulate these changes. Bioenergetics measurements were taken in quiescent\n NHF<\/jats:styled-content>\n s from younger (newborn, 3\u2010day, 5\u2010month, and 1\u2010year) and older (58\u2010, 61\u2010, 63\u2010, 68\u2010, and 70\u2010year) healthy donors as well as\n NHF<\/jats:styled-content>\n s from the same individual at different ages (29, 36, and 46\u00a0years). Results show significant changes in cellular metabolism during aging of quiescent\n NHF<\/jats:styled-content>\n s: Old\n NHF<\/jats:styled-content>\n s exhibit a significant decrease in glycolytic flux and lactate levels, and increase in oxygen consumption rate (\n OCR<\/jats:styled-content>\n ) and\n ATP<\/jats:styled-content>\n levels compared to young\n NHF<\/jats:styled-content>\n s. Results from the Seahorse\n XF<\/jats:styled-content>\n Cell Mito Stress Test show that old\n NHF<\/jats:styled-content>\n s with a lower Bioenergetic Health Index (\n BHI<\/jats:styled-content>\n ) are more prone to oxidative stress compared to young\n NHF<\/jats:styled-content>\n s with a higher\n BHI<\/jats:styled-content>\n . The increase in\n OCR<\/jats:styled-content>\n in old\n NHF<\/jats:styled-content>\n s is associated with a shift in mitochondrial dynamics more toward fusion. Genetic knockdown of mitofusin 1 (\n MFN<\/jats:styled-content>\n 1) and optic atrophy 1 (\n OPA<\/jats:styled-content>\n 1) in old\n NHF<\/jats:styled-content>\n s decreased\n OCR<\/jats:styled-content>\n and shifted metabolism more toward glycolysis. Downregulation of\n MFN<\/jats:styled-content>\n 1 and\n OPA<\/jats:styled-content>\n 1 also suppressed the radiation\u2010induced increase in doubling time of\n NHF<\/jats:styled-content>\n s. In summary, results show that a metabolic shift from glycolysis in young to mitochondrial respiration in old\n NHF<\/jats:styled-content>\n s occurs during chronological lifespan, and\n MFN<\/jats:styled-content>\n 1 and\n OPA<\/jats:styled-content>\n 1 regulate this process.\n <\/jats:p>","DOI":"10.1111\/acel.12649","type":"journal-article","created":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T03:46:41Z","timestamp":1501472801000},"page":"1136-1145","source":"Crossref","is-referenced-by-count":74,"title":["Mitofusin 1 and optic atrophy 1 shift metabolism to mitochondrial respiration during aging"],"prefix":"10.1111","volume":"16","author":[{"given":"Jyung Mean","family":"Son","sequence":"first","affiliation":[{"name":"Free Radical and Radiation Biology Division Department of Radiation Oncology University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab H.","family":"Sarsour","sequence":"additional","affiliation":[{"name":"Free Radical and Radiation Biology Division Department of Radiation Oncology University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurag","family":"Kakkerla Balaraju","sequence":"additional","affiliation":[{"name":"Free Radical and Radiation Biology Division Department of Radiation Oncology University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Fussell","sequence":"additional","affiliation":[{"name":"Free Radical and Radiation Biology Division Department of Radiation Oncology University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Kalen","sequence":"additional","affiliation":[{"name":"Free Radical and Radiation Biology Division Department of Radiation Oncology University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett A.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Free Radical and Radiation Biology Division Department of Radiation Oncology University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry R.","family":"Buettner","sequence":"additional","affiliation":[{"name":"Free Radical and Radiation Biology Division Department of Radiation Oncology University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhat C.","family":"Goswami","sequence":"additional","affiliation":[{"name":"Free Radical and Radiation Biology Division Department of Radiation Oncology University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201308006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212754200"},{"key":"e_1_2_9_4_1","first-page":"219","article-title":"Comparative morphological study of age related mitochondrial changes of the lymphocytes and skeletal muscle cells","volume":"35","author":"Beregi E","year":"1987","journal-title":"Acta Morphol. 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