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J Neurovirol. 2016 Jun;22(3):366-75. doi: 10.1007/s13365-015-0406-3. Epub 2015 Dec 21.

Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders.

Author information

1
Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA. ajlevine@mednet.ucla.edu.
2
UCLA-Reed Neurological Research Center, 710 Westwood Plaza, Room 2-250, Los Angeles, CA, 90095, USA. ajlevine@mednet.ucla.edu.
3
Department of Human Genetics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
4
Department of Psychiatry, San Diego School of Medicine, University of California, La Jolla, CA, USA.
5
Departments of Neuroscience and Pathology, San Diego School of Medicine, University of California, La Jolla, CA, USA.
6
Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
7
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
8
Departments of Human Genetics and Biostatistics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.

Abstract

HIV infection leads to age-related conditions in relatively young persons. HIV-associated neurocognitive disorders (HAND) are considered among the most prevalent of these conditions. To study the mechanisms underlying this disorder, researchers need an accurate method for measuring biological aging. Here, we apply a recently developed measure of biological aging, based on DNA methylation, to the study of biological aging in HIV+ brains. Retrospective analysis of tissue bank specimens and pre-mortem data was carried out. Fifty-eight HIV+ adults underwent a medical and neurocognitive evaluation within 1 year of death. DNA was obtained from occipital cortex and analyzed with the Illumina Infinium Human Methylation 450K platform. Biological age determined via the epigenetic clock was contrasted with chronological age to obtain a measure of age acceleration, which was then compared between those with HAND and neurocognitively normal individuals. The HAND and neurocognitively normal groups did not differ with regard to demographic, histologic, neuropathologic, or virologic variables. HAND was associated with accelerated aging relative to neurocognitively normal individuals, with average relative acceleration of 3.5 years. Age acceleration did not correlate with pre-mortem neurocognitive functioning or HAND severity. This is the first study to demonstrate that the epigenetic age of occipital cortex samples is associated with HAND status in HIV+ individuals pre-mortem. While these results suggest that the increased risk of a neurocognitive disorder due to HIV might be mediated by an epigenetic aging mechanism, future studies will be needed to validate the findings and dissect causal relationships and downstream effects.

KEYWORDS:

Epigenetic; Epigenetic clock; HANA; HAND; HIV; HIV-associated neurocognitive disorder

PMID:
26689571
PMCID:
PMC4900944
DOI:
10.1007/s13365-015-0406-3
[Indexed for MEDLINE]
Free PMC Article

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