Accelerated epigenetic aging in adolescents from low-income households is associated with altered development of brain s
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ORIGINAL ARTICLE
Accelerated epigenetic aging in adolescents from low-income households is associated with altered development of brain structures Jacqueline Hoare 1 & Dan J. Stein 1,2 & Sarah J. Heany 1 & Jean-Paul Fouche 1 & Nicole Phillips 1 & Sebnem Er 3 & Landon Myer 4,5 & Heather J. Zar 6,7 & Steve Horvath 8,9 & Andrew J. Levine 2,10 Received: 5 November 2019 / Accepted: 23 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The relationship between cognitive performance, macro and microstructural brain anatomy and accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock in healthy adolescents has not been studied. Healthy adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study were studied cross sectionally. The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 44 adolescents aged 9 to 12 years old. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration residual (AAR) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent neurocognitive testing, T1 structural magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI). Correlation tests were run between the two epigenetic aging measures and 10 cognitive functioning domains, to assess for differences in cognitive performance as epigenetic aging increases. In order to investigate the associations of epigenetic age acceleration on brain structure, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, and cortical surface area, as well as DTI measures of white matter microstructural integrity. In addition to negatively affecting two cognitive domains, visual memory (p = .026) and visual spatial acuity (p = .02), epigenetic age acceleration was associated with alterations of brain volumes, cortical thickness, cortical surface areas and abnormalities in neuronal microstructure in a range of regions. Stress was a significant predictor (p = .029) of AAR. Understanding the drivers of epigenetic age acceleration in adolescents could lead to valuable insights into the development of neurocognitive impairment in adolescents. Keywords DNA methylation . Epigenetic clock . MRI . DTI . Adolescent
* Jacqueline Hoare [email protected] 1
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Department of Psychiatry and Mental Health, University of Cape Town, Groote Schuur Hospital, Observatory, Cape Town 7925, South Africa SA MRC Unit on Risk & Resilience in Mental Disorders, Cape Town, South Africa Department of Statistics, University of Cape Town, Rondebosch, Cape Town, South Africa Centre for Infectious Disease Epidemiology and Research, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa
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Division of Epidemiology and Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa
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Department of Pa
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