{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:50:42Z","timestamp":1790286642765,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","funder":[{"DOI":"10.13039\/100000738","name":"US Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 RX002790"],"award-info":[{"award-number":["I01 RX002790"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AI050409"],"award-info":[{"award-number":["P30 AI050409"]}],"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":["R01DK125187"],"award-info":[{"award-number":["R01DK125187"]}],"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":["R01DA047820"],"award-info":[{"award-number":["R01DA047820"]}],"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":["R01DA052846"],"award-info":[{"award-number":["R01DA052846"]}],"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":["R01DA042691"],"award-info":[{"award-number":["R01DA042691"]}],"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":["R01DA047063"],"award-info":[{"award-number":["R01DA047063"]}],"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":["U24AA020794"],"award-info":[{"award-number":["U24AA020794"]}],"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":["U01AA020790"],"award-info":[{"award-number":["U01AA020790"]}],"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":["U24-AA022001"],"award-info":[{"award-number":["U24-AA022001"]}],"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":["U10 AA013566"],"award-info":[{"award-number":["U10 AA013566"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005326","name":"Yale University","doi-asserted-by":"publisher","award":["K01HL134147"],"award-info":[{"award-number":["K01HL134147"]}],"id":[{"id":"10.13039\/100005326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005326","name":"Yale University","doi-asserted-by":"publisher","award":["P30AG031679"],"award-info":[{"award-number":["P30AG031679"]}],"id":[{"id":"10.13039\/100005326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005326","name":"Yale University","doi-asserted-by":"publisher","award":["P30AI060354"],"award-info":[{"award-number":["P30AI060354"]}],"id":[{"id":"10.13039\/100005326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Biomarkers that provide insight into drivers of aging are needed for people with human immunodeficiency virus (PWH). The study objective was to determine if epigenetic age acceleration (EAA) markers are associated with physiologic frailty measured by the Veterans Aging Cohort Study (VACS) Index and predict all-cause mortality for PWH.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Epigenome-wide DNA methylation was profiled in VACS total white blood cell samples collected during 2005\u20132007 from 531 PWH to generate 6 established markers of EAA. The association of each EAA marker was tested with VACS Index 2.0. All-cause mortality was assessed over 10 years. For each EAA marker, the hazard ratio per increased year was determined using Cox regression. To evaluate mortality discrimination, C-statistics were derived.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Participants were mostly men (98.5%) and non-Hispanic Black (84.4%), with a mean age of 52.4 years (standard deviation [SD], 7.8 years). Mean VACS Index score was 59.3 (SD, 16.4) and 136 deaths occurred over a median follow-up of 8.7 years. Grim age acceleration (AA), PhenoAA, HannumAA, and extrinsic epigenetic AA were associated with the VACS Index and mortality. HorvathAA and intrinsic epigenetic AA were not associated with either outcome. GrimAA had the greatest mortality discrimination among EAA markers and predicted mortality independently of the VACS Index. One-year increase in GrimAA was associated with a 1-point increase in VACS Index and a 10% increased hazard for mortality.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The observed associations between EAA markers with physiologic frailty and mortality support future research to provide mechanistic insight into the accelerated aging process and inform interventions tailored to PWH for promoting increased healthspan.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac656","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T02:57:22Z","timestamp":1660618642000},"page":"e638-e644","source":"Crossref","is-referenced-by-count":23,"title":["Epigenetic Age Acceleration Markers Are Associated With Physiologic Frailty and All-Cause Mortality in People With Human Immunodeficiency Virus"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3337-9366","authenticated-orcid":false,"given":"Krisann K","family":"Oursler","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Virginia Tech Carilion School of Medicine and Veterans Affairs Salem Healthcare System , Roanoke, Virginia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8409-4689","authenticated-orcid":false,"given":"Vincent C","family":"Marconi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine and Rollins School of Public Health , Atlanta, Georgia , USA"},{"name":"Veterans Affairs Atlanta Healthcare System , Decatur, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine , West Haven, Connecticut , USA"},{"name":"Veterans Affairs Connecticut Healthcare System , West Haven, Connecticut , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8738-2838","authenticated-orcid":false,"given":"Monty","family":"Montano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1505-6384","authenticated-orcid":false,"given":"Kaku","family":"So-Armah","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C","family":"Justice","sequence":"additional","affiliation":[{"name":"Veterans Affairs Connecticut Healthcare System , West Haven, Connecticut , USA"},{"name":"Department of Medicine, Yale School of Medicine , West Haven, Connecticut , USA"},{"name":"Division of Health Policy, Yale School of Public Health, West Haven, Connecticut , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan V","family":"Sun","sequence":"additional","affiliation":[{"name":"Veterans Affairs Atlanta Healthcare System , Decatur, Georgia , USA"},{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"2023053119003153000_ciac656-B1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1097\/QAI.0b013e318278f3fa","article-title":"Risk factors for hospitalization and medical intensive care unit (MICU) 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