Neuroepigenetic Signatures of Age and Sex in the Living Human Brain

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Jul 5

PMID 31270332

Citations 18

Authors

Tonya M Gilbert

Nicole R Zurcher

Mary C Catanese

Chieh-En J Tseng

Maria A Di Biase

Amanda E Lyall

Baileigh G Hightower

Anjali J Parmar

Anisha Bhanot

Christine J Wu

Matthew L Hibert

Minhae Kim

Umar Mahmood

Steven M Stufflebeam

Frederick A Schroeder

Changning Wang

Joshua L Roffman

Daphne J Holt

Douglas N Greve

Ofer Pasternak

Marek Kubicki

Hsiao-Ying Wey

Jacob M Hooker

Affiliations

Soon will be listed here.

Abstract

Age- and sex-related alterations in gene transcription have been demonstrated, however the underlying mechanisms are unresolved. Neuroepigenetic pathways regulate gene transcription in the brain. Here, we measure in vivo expression of the epigenetic enzymes, histone deacetylases (HDACs), across healthy human aging and between sexes using [C]Martinostat positron emission tomography (PET) neuroimaging (n = 41). Relative HDAC expression increases with age in cerebral white matter, and correlates with age-associated disruptions in white matter microstructure. A post mortem study confirmed that HDAC1 and HDAC2 paralogs are elevated in white matter tissue from elderly donors. There are also sex-specific in vivo HDAC expression differences in brain regions associated with emotion and memory, including the amygdala and hippocampus. Hippocampus and white matter HDAC expression negatively correlates with emotion regulation skills (n = 23). Age and sex are associated with HDAC expression in vivo, which could drive age- and sex-related transcriptional changes and impact human behavior.

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