{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T23:25:24Z","timestamp":1761261924244,"version":"build-2065373602"},"reference-count":34,"publisher":"Georg Thieme Verlag KG","issue":"CP","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biotest AG"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TH Open"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hemophilia is a rare X-linked bleeding disorder leading to recurrent hemarthroses, hemophilic arthropathy, and impaired quality of life. A chronic lifelong disease, hemophilia might be associated with accelerated biological aging. Here, we investigated whether biological age derived from epigenetic age estimators differs in hemophilia.<\/jats:p>\n                  <jats:p>We collected blood samples from men with severe (&lt;1\u2009IU\/dL; PWSH, n\u2009=\u200920) or mild hemophilia (\u22655\u2009IU\/dL; PWMH, n\u2009=\u200920), and age-matched healthy male controls (n\u2009=\u200920). DNA methylation of cytosine\u2013phosphate\u2013guanine (CpG) dinucleotides at five genes (ASPA, ITGA2B, PDE4C, FHL2, CCDC10SB) was measured by bisulfite pyrosequencing. Biological age was estimated using two epigenetic aging signatures, each including three CpGs. We investigated differences in biological age and the rate of biological aging between study groups using separate linear regressions on chronological age and study group without and with an interaction, respectively.<\/jats:p>\n                  <jats:p>Deviations of epigenetic from chronological age were high for both 3-CpG age estimators, with results suggesting systematic overprediction. In both linear regressions using the two 3-CpG estimates, respectively, evidence for a different rate of biological aging in severe hemophilia was weak. The rate of biological aging in PWSH was 0.24 (95% CI, 0.01\u20130.48) and 0.21 (0.04\u20130.37) higher compared with PWMH, and 0.05 (\u22120.19\u20130.29) and 0.17 (\u22120.00\u20130.34) higher compared with healthy controls, respectively. Hemophilic arthropathy was associated with an increased rate of biological aging.<\/jats:p>\n                  <jats:p>Evidence for a difference in epigenetic aging as reflected by two 3-CpG estimators in severe compared with mild hemophilia or healthy controls was weak.<\/jats:p>","DOI":"10.1055\/a-2713-2910","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T23:06:17Z","timestamp":1759273577000},"source":"Crossref","is-referenced-by-count":0,"special_numbering":"S","title":["Epigenetic Aging Signatures in People with Hemophilia"],"prefix":"10.1055","volume":"09","author":[{"given":"Daniel","family":"Kraemmer","sequence":"additional","affiliation":[{"name":"Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafaela","family":"Vostatek","sequence":"additional","affiliation":[{"name":"Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Trappl","sequence":"additional","affiliation":[{"name":"Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Gebhart","sequence":"additional","affiliation":[{"name":"Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Pabinger","sequence":"additional","affiliation":[{"name":"Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cihan","family":"Ay","sequence":"additional","affiliation":[{"name":"Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-021-00278-x","article-title":"Haemophilia","volume":"7","author":"E Berntorp","year":"2021","journal-title":"Nat Rev Dis Primers"},{"issue":"06","key":"ref2","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/j.1365-2516.2011.02539.x","article-title":"Clinical severity of haemophilia A: Does the classification of the 1950s still stand?","volume":"17","author":"I EM Den Uijl","year":"2011","journal-title":"Haemophilia"},{"issue":"11","key":"ref3","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1111\/jth.12672","article-title":"Definitions in hemophilia: Communication from the SSC of the ISTH","volume":"12","author":"V S Blanchette","year":"2014","journal-title":"J Thromb Haemost"},{"issue":"09","key":"ref4","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1111\/j.1538-7836.2010.03962.x","article-title":"Blood-induced joint disease: The pathophysiology of hemophilic arthropathy","volume":"8","author":"L A Valentino","year":"2010","journal-title":"J Thromb Haemost"},{"issue":"S 01","key":"ref5","first-page":"6","article-title":"Mortality in congenital hemophilia A - a systematic literature review","volume":"19 Suppl 1","author":"C RM Hay","year":"2021","journal-title":"J Thromb Haemost"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/hae.14046","article-title":"WFH Guidelines for the Management of Hemophilia, 3rd edition","volume":"26 Suppl 6","author":"A Srivastava","year":"2020","journal-title":"Haemophilia"},{"issue":"03","key":"ref7","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1111\/hae.14989","article-title":"Anxiety and depression among adults with haemophilia A: Patient and physician reported symptoms from the real-world European CHESS II study","volume":"30","author":"E Ferri Grazzi","year":"2024","journal-title":"Haemophilia"},{"issue":"02","key":"ref8","doi-asserted-by":"crossref","first-page":"e181","DOI":"10.1055\/s-0044-1785524","article-title":"Disease burden, clinical outcomes, and quality of life in people with hemophilia A without inhibitors in Europe: Analyses from CHESS II\/CHESS PAEDs","volume":"8","author":"P Chowdary","year":"2024","journal-title":"TH Open"},{"issue":"10","key":"ref9","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/nm.2942","article-title":"A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model","volume":"18","author":"T Kitazawa","year":"2012","journal-title":"Nat Med"},{"issue":"04","key":"ref10","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1056\/NEJMoa2209226","article-title":"Efanesoctocog alfa prophylaxis 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Open"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2713-2910.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T23:21:40Z","timestamp":1761261700000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2713-2910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,30]]},"references-count":34,"journal-issue":{"issue":"CP","published-online":{"date-parts":[[2025,1,27]]},"published-print":{"date-parts":[[2025]]}},"alternative-id":["a27132910"],"URL":"https:\/\/doi.org\/10.1055\/a-2713-2910","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2512-9465"],"issn-type":[{"type":"electronic","value":"2512-9465"}],"subject":[],"published-other":{"date-parts":[[2025,9,30]]},"published":{"date-parts":[[2025,9,30]]}}}