Persistent accelerated epigenetic ageing in a longitudinal cohort of vertically infected HIV-positive adolescents

Sarah J. Heany, Andrew J. Levine, Maia Lesosky, Nicole Phillips, Jean Paul Fouche, Landon Myer, Heather J. Zar, Dan J. Stein, Steve Horvath, Jacqueline Hoare

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

We have previously shown accelerated ageing in adolescents perinatally infected with HIV (PHIV +), based on discrepancies between epigenetic and chronological age. The current study examines follow-up longitudinal patterns of epigenetic ageing and the association of epigenetic ageing with cognition as well as whole brain structure changes in PHIV + and healthy controls enrolled in the Cape Town Adolescent Antiretroviral Cohort Study (CTAAC). The Illumina EPIC array was used to generate blood DNA methylation data from 60 PHIV + adolescents and 36 age-matched controls aged 9–12 years old at baseline and again at a 36-month follow-up. Epigenetic clock software estimated two measures of epigenetic age acceleration: extrinsic epigenetic accelerated ageing (EEAA) and age acceleration difference (AAD) at both time points. At follow-up, each participant completed neuropsychological testing, structural magnetic resonance imaging, and diffusion tensor imaging. At follow-up, PHIV infection remains associated with increased EEAA and AAD. Accelerated epigenetic ageing remained positively associated with viral load and negatively associated with CD4 ratio. EEAA was positively associated with whole brain grey matter volume and alterations in whole brain white matter integrity. AAD and EEAA were not associated with cognitive function within the PHIV + group. Measures of epigenetic ageing, as detected in DNA methylation patterns, remain increased in PHIV + adolescents across a 36-month period. Associations between epigenetic ageing measures, viral biomarkers, and alterations in brain micro- and macrostructure also persist at 36-month follow-up. Further study should determine if epigenetic age acceleration is associated with cognitive functional changes due to brain alterations in later life.

Original languageEnglish
Pages (from-to)272-282
Number of pages11
JournalJournal of NeuroVirology
Volume29
Issue number3
DOIs
StatePublished - Jun 2023
Externally publishedYes

Keywords

  • Accelerated ageing
  • DNA methylation
  • Epigenetic clock
  • Perinatal HIV

Fingerprint

Dive into the research topics of 'Persistent accelerated epigenetic ageing in a longitudinal cohort of vertically infected HIV-positive adolescents'. Together they form a unique fingerprint.

Cite this