title: Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders.
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.
authors.affiliation: Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA. ajlevine@mednet.ucla.edu.|UCLA-Reed Neurological Research Center, 710 Westwood Plaza, Room 2-250, Los Angeles, CA, 90095, USA. ajlevine@mednet.ucla.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Levine
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Quach
authors.affiliation: Department of Psychiatry, San Diego School of Medicine, University of California, La Jolla, CA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Moore
authors.affiliation: Department of Psychiatry, San Diego School of Medicine, University of California, La Jolla, CA, USA.
authors.forename: Cristian L
authors.initials: CL
authors.lastname: Achim
authors.affiliation: Department of Psychiatry, San Diego School of Medicine, University of California, La Jolla, CA, USA.
authors.forename: Virawudh
authors.initials: V
authors.lastname: Soontornniyomkij
authors.affiliation: Departments of Neuroscience and Pathology, San Diego School of Medicine, University of California, La Jolla, CA, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
authors.forename: Elyse J
authors.initials: EJ
authors.lastname: Singer
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gelman
authors.affiliation: Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Nemanim
authors.affiliation: Departments of Human Genetics and Biostatistics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
mesh_terms: D000054:Acceleration; D000328:Adult; D000375:Aging / Q000235:genetics* / Q000473:pathology; D001344:Autopsy; D060825:Cognitive Dysfunction / Q000150:complications / Q000235:genetics* / Q000821:virology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009778:Occipital Lobe / Q000378:metabolism* / Q000821:virology; D012189:Retrospective Studies
keywords: Epigenetic; Epigenetic clock; HANA; HAND; HIV; HIV-associated neurocognitive disorder