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

Autor: Benjamin B. Gelman, Austin Quach, Eliezer Masliah, Elyse J. Singer, Andrew J. Levine, Natasha Nemanim, David J. Moore, Virawudh Soontornniyomkij, Cristian L. Achim, Steve Horvath
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Oncology
Aging
Neurology
Epigenetic clock
HIV Infections
HIV-associated neurocognitive disorder
Epigenesis
Genetic
2.1 Biological and endogenous factors
Aetiology
Epigenetic
Middle Aged
Mental Health
Infectious Diseases
Medical Microbiology
DNA methylation
HIV/AIDS
Female
Occipital Lobe
Autopsy
Psychology
Adult
medicine.medical_specialty
Acceleration
Clinical Sciences
HANA
HAND
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Genetic
Clinical Research
Virology
Internal medicine
Genetics
medicine
Humans
Cognitive Dysfunction
Epigenetics
Retrospective Studies
Mechanism (biology)
Neurosciences
HIV
Retrospective cohort study
DNA Methylation
medicine.disease
Brain Disorders
030104 developmental biology
Neurology (clinical)
Occipital lobe
Neuroscience
Neurocognitive
Epigenesis
Zdroj: Levine, AJ; Quach, A; Moore, DJ; Achim, CL; Soontornniyomkij, V; Masliah, E; et al.(2016). Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders. JOURNAL OF NEUROVIROLOGY, 22(3), 366-375. doi: 10.1007/s13365-015-0406-3. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/1qs5j2z0
Journal of neurovirology, vol 22, iss 3
DOI: 10.1007/s13365-015-0406-3.
Popis: 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 1year 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 3.5years. 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.
Databáze: OpenAIRE
Externí odkaz: