dc.date.accessioned | 2020-06-09T18:26:56Z | |
dc.date.available | 2020-06-09T18:26:56Z | |
dc.date.created | 2020-01-13T16:15:44Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Fang, Evandro Fei Nilsen, Hilde Loge Rusten, Tor Erik Khezri, Rojyar Aman, Yahyah Sengupta, Tanima Hindkjær Lautrup, Sofie Hou, Yujun Bohr, Vilhelm A. Jensen, Martin Borch Yang, Beimeng Caponio, Domenica Demarest, Tyler G. Figueroa, David Morevati, Marya Lee, Ho-Joon Kato, Hisaya Kassahun, Henok Lee, Jong-Hyuk Filippelli, Deborah Okur, Mustafa Nazir Mangerich, Aswin Croteau, Deborah L. Maezawa, Yoshiro Lyssiotis, Costas A. Tao, Jun Yokoto, Koutaro Mattson, Mark P. Jasper, Heinrich . NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome.. Nature Communications. 2019 | |
dc.identifier.uri | http://hdl.handle.net/10852/76832 | |
dc.description.abstract | Metabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD+, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models. WRN regulates transcription of a key NAD+ biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1). NAD+ repletion restores NAD+ metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD+ repletion remarkably extends lifespan and delays accelerated aging, including stem cell dysfunction, in Caenorhabditis elegans and Drosophila melanogaster models of WS. Our findings suggest that accelerated aging in WS is mediated by impaired mitochondrial function and mitophagy, and that bolstering cellular NAD+ levels counteracts WS phenotypes. | |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. | |
dc.type | Journal article | |
dc.creator.author | Fang, Evandro Fei | |
dc.creator.author | Nilsen, Hilde Loge | |
dc.creator.author | Rusten, Tor Erik | |
dc.creator.author | Khezri, Rojyar | |
dc.creator.author | Aman, Yahyah | |
dc.creator.author | Sengupta, Tanima | |
dc.creator.author | Hindkjær Lautrup, Sofie | |
dc.creator.author | Hou, Yujun | |
dc.creator.author | Bohr, Vilhelm A. | |
dc.creator.author | Jensen, Martin Borch | |
dc.creator.author | Yang, Beimeng | |
dc.creator.author | Caponio, Domenica | |
dc.creator.author | Demarest, Tyler G. | |
dc.creator.author | Figueroa, David | |
dc.creator.author | Morevati, Marya | |
dc.creator.author | Lee, Ho-Joon | |
dc.creator.author | Kato, Hisaya | |
dc.creator.author | Kassahun, Henok | |
dc.creator.author | Lee, Jong-Hyuk | |
dc.creator.author | Filippelli, Deborah | |
dc.creator.author | Okur, Mustafa Nazir | |
dc.creator.author | Mangerich, Aswin | |
dc.creator.author | Croteau, Deborah L. | |
dc.creator.author | Maezawa, Yoshiro | |
dc.creator.author | Lyssiotis, Costas A. | |
dc.creator.author | Tao, Jun | |
dc.creator.author | Yokoto, Koutaro | |
dc.creator.author | Mattson, Mark P. | |
dc.creator.author | Jasper, Heinrich | |
cristin.unitcode | 185,51,1,5 | |
cristin.unitname | Avdeling for komparativ medisin | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1771780 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature Communications&rft.volume=&rft.spage=&rft.date=2019 | |
dc.identifier.jtitle | Nature Communications | |
dc.identifier.volume | 10 | |
dc.identifier.issue | 1 | |
dc.identifier.doi | https://doi.org/10.1038/s41467-019-13172-8 | |
dc.identifier.urn | URN:NBN:no-79940 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2041-1723 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/76832/1/NAD%252Baugmentation%2Brestores%2Bmitophagy%2Band%2Blimitsaccelerated%2Baging%2Bin%2BWerner%2Bsyndrome.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 5284 | |