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

TitleAccelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders.
Publication TypeJournal Article
Year of Publication2016
AuthorsLevine, AJ, Quach, A, Moore, DJ, Achim, CL, Soontornniyomkij, V, Masliah, E, Singer, EJ, Gelman, B, Nemanim, N, Horvath, S
JournalJ Neurovirol
Date Published2016 06
KeywordsAcceleration, Adult, Aging, Autopsy, Cognitive Dysfunction, DNA Methylation, Epigenesis, Genetic, Female, HIV Infections, Humans, Internal, Male, Middle Aged, Occipital Lobe, Retrospective Studies

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.

Alternate JournalJ Neurovirol
PubMed ID26689571
PubMed Central IDPMC4900944
Grant ListU24 MH100929 / MH / NIMH NIH HHS / United States
R21 AG046954 / AG / NIA NIH HHS / United States
U01 MH083500 / MH / NIMH NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
R24 MH059745 / MH / NIMH NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
R24 NS038841 / NS / NINDS NIH HHS / United States
R01 DA030913 / DA / NIDA NIH HHS / United States
R01 MH096648 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
M01 RR000827 / RR / NCRR NIH HHS / United States