{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T09:07:57Z","timestamp":1769072877998,"version":"3.49.0"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:00:00Z","timestamp":1674864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P40 OD010440"],"award-info":[{"award-number":["P40 OD010440"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Qatar National Research Fund and Qatar Genome Program","award":["#PPM2-0226-170020"],"award-info":[{"award-number":["#PPM2-0226-170020"]}]},{"name":"Qatar National Research Fund and Qatar Genome Program","award":["R01CA210916"],"award-info":[{"award-number":["R01CA210916"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Berardinelli\u2013Seip congenital lipodystrophy type 2 (CGL2) is a very rare human genetic disorder with potential significance to the understanding of the pathobiology of aging. CGL2 patients display characteristic progeroid features and suffer from type 2 diabetes, insulin resistance and fatty liver. In this study, we profiled genome-wide DNA methylation levels in CGL2 patients with BSCL2 mutations to study epigenetic age acceleration and DNA methylation alterations. This analysis revealed significant age acceleration in blood DNA of CGL2 patients using both first- and second-generation epigenetic clocks. We also observed a shortened lifespan of Caenorhabditis elegans following knockdown of the BSCL2 homolog seip-1 on a daf-16\/forkhead box, class O mutant background. DNA methylation analysis revealed significant differentially methylated sites enriched for lyase activity, kinase regulator activity, protein kinase regulator activity and kinase activator activity. We could also observe significant hypomethylation in the promoter of the dual specificity phosphatase 22 gene when comparing CGL2 patients versus controls. We conclude that in line with the observed progeroid features, CGL2 patients exhibit significant epigenetic age acceleration and DNA methylation alterations that might affect pathways\/genes of potential relevance to the disease.<\/jats:p>","DOI":"10.1093\/hmg\/ddad016","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T11:33:36Z","timestamp":1675078416000},"page":"1826-1835","source":"Crossref","is-referenced-by-count":16,"title":["Accelerated epigenetic aging and DNA methylation alterations in Berardinelli\u2013Seip congenital lipodystrophy"],"prefix":"10.1093","volume":"32","author":[{"given":"Abeer","family":"Qannan","sequence":"first","affiliation":[{"name":"Hamad Bin Khalifa University, Qatar Foundation College of Health and Life Sciences, , Doha 34110 , Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosra","family":"Bejaoui","sequence":"additional","affiliation":[{"name":"Hamad Bin Khalifa University, Qatar Foundation College of Health and Life Sciences, , Doha 34110 , Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Izadi","sequence":"additional","affiliation":[{"name":"Hamad Bin Khalifa University, Qatar Foundation College of Health and Life Sciences, , Doha 34110 , Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noha A","family":"Yousri","sequence":"additional","affiliation":[{"name":"Genetic Medicine, Weill Cornell Medicine-Qatar , Doha , Qatar"},{"name":"Alexandria University Computer and Systems Engineering, , Alexandria , Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleem","family":"Razzaq","sequence":"additional","affiliation":[{"name":"Hamad Bin Khalifa University, Qatar Foundation College of Health and Life Sciences, , Doha 34110 , Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6034-5746","authenticated-orcid":false,"given":"Colette","family":"Christiansen","sequence":"additional","affiliation":[{"name":"King\u2019s College London Department of Twin Research and Genetic Epidemiology, , London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George M","family":"Martin","sequence":"additional","affiliation":[{"name":"University of Washington Department of Laboratory Medicine and Pathology, , Seattle, WA 98105 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordana T","family":"Bell","sequence":"additional","affiliation":[{"name":"King\u2019s College London Department of Twin Research and Genetic Epidemiology, , London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Horvath","sequence":"additional","affiliation":[{"name":"Altos Labs , San Diego , USA"},{"name":"University of California Los Angeles Department of Human Genetics, David Geffen School of Medicine, , Los Angeles, CA 90095 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Oshima","sequence":"additional","affiliation":[{"name":"University of Washington Department of Laboratory Medicine and Pathology, , Seattle, WA 98105 , USA"},{"name":"Chiba University Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, , Chiba , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0714-2469","authenticated-orcid":false,"given":"Andre","family":"Megarbane","sequence":"additional","affiliation":[{"name":"Lebanese American University Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, , Byblos , Lebanon"},{"name":"Institut J\u00e9r\u00f4me Lejeune , Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Ericsson","sequence":"additional","affiliation":[{"name":"Hamad Bin Khalifa University, Qatar Foundation College of Health and Life Sciences, , Doha 34110 , Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehsan","family":"Pourkarimi","sequence":"additional","affiliation":[{"name":"Hamad Bin Khalifa University, Qatar Foundation College of Health and Life Sciences, , Doha 34110 , Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3420-8531","authenticated-orcid":false,"given":"Nady","family":"El Hajj","sequence":"additional","affiliation":[{"name":"Hamad Bin Khalifa University, Qatar Foundation College of Health and Life Sciences, , Doha 34110 , Qatar"},{"name":"Hamad Bin Khalifa University, Qatar Foundation College of Science and Engineering, , Doha 34110 , Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"2023051907034534700_ref1","doi-asserted-by":"crossref","DOI":"10.1016\/j.lpm.2021.104085","article-title":"Complications of lipodystrophy syndromes","volume":"50","author":"Akinci","year":"2021","journal-title":"Presse Med."},{"key":"2023051907034534700_ref2","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1056\/NEJMra025261","article-title":"Acquired and inherited lipodystrophies","volume":"350","author":"Garg","year":"2004","journal-title":"N. 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