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

Journal: Journal of neurovirology

Volume: 29

Issue: 3

Year of Publication: 2023

Affiliated Institutions:  SA MRC Unit On Risk & Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. s.heany@uct.ac.za. Department of Neurology, David Geffen School of Medicineat the , University of California, Los Angeles, Los Angeles, CA, USA. Division of Epidemiology and Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa. SA MRC Unit On Risk & Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. Centre for Infectious Disease Epidemiology and Research, Division of Epidemiology and Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa. Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, Cape Town, South Africa. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Abstract summary 

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.

Authors & Co-authors:  Heany Sarah J SJ Levine Andrew J AJ Lesosky Maia M Phillips Nicole N Fouche Jean-Paul JP Myer Landon L Zar Heather J HJ Stein Dan J DJ Horvath Steve S Hoare Jacqueline J

Study Outcome 

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Statistics
Citations :  Aberg JA. Aging, inflammation, and HIV infection. Topics in Antiviral Medicine. 2012;20(3):101.
Authors :  10
Identifiers
Doi : 10.1007/s13365-023-01130-6
SSN : 1538-2443
Study Population
Male,Female
Mesh Terms
Humans
Other Terms
Accelerated ageing;DNA methylation;Epigenetic clock;Perinatal HIV
Study Design
Cohort Study,Longitudinal Study,Cross Sectional Study
Study Approach
Country of Study
Publication Country
United States