title: Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion.
abstract: Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform. Methylation aging was assessed using the Horvath method. Telomere length significantly decreased between T1 and T2 (227±46 at T1 vs. 201±48 kbp/genome at T2, p=0.045), while no differences were observed between T2 and T3 (201±48 at T2 vs. 186±27 kbp/genome at T3, p=0.244). Methylation aging as measured by the age acceleration residual increased over the time course of HIV infection (p=0.035). CpG sites corresponding toPCBP2andCSRNP1were differentially methylated between T1 and T2 at a q-value <0.05. Telomere shortening and methylation changes can therefore be observed in the short-term period immediately following HIV seroconversion. Further studies to confirm these results in larger sample sizes and to compare these results to non-HIV and non-injection drug users are warranted.
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.|Division of Respiratory Medicine, Department of Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.|BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Leung
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
authors.forename: Nick
authors.initials: N
authors.lastname: Fishbane
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, V5Z 4H4, Canada.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Jones
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, V5Z 4H4, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Morin
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
authors.forename: Stella
authors.initials: S
authors.lastname: Xu
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
authors.forename: Joseph Cy
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, V5Z 4H4, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: MacIsaac
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Milloy
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.|Department of Medicine, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
authors.forename: Kanna
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
authors.forename: Julio
authors.initials: J
authors.lastname: Montaner
authors.affiliation: Departments of Human Genetics and Biostatistics, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, V5Z 4H4, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Kobor
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.|Division of Respiratory Medicine, Department of Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, V5Z 4H4, Canada.
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.affiliation: Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.|Division of Respiratory Medicine, Department of Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
authors.forename: S F Paul
authors.initials: SF
authors.lastname: Man
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000235:genetics; D000069078:Seroconversion / Q000235:genetics*; D015819:Substance Abuse, Intravenous / Q000821:virology; D059506:Telomere Shortening
chemical_list: D051017:Apoptosis Regulatory Proteins; C434543:CSRNP1 protein, human; C501903:PCBP2 protein, human; D016601:RNA-Binding Proteins
keywords: HIV; aging; methylation; seroconversion; telomere