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Neuroepigenetic signatures of age and sex in the living human brain.

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 [11C]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.

SUBMITTER: Gilbert TM

PROVIDER: S-EPMC6610136 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Neuroepigenetic signatures of age and sex in the living human brain.

Gilbert Tonya M TM Zürcher Nicole R NR Catanese Mary C MC Tseng Chieh-En J CJ Di Biase Maria A MA Lyall Amanda E AE Hightower Baileigh G BG Parmar Anjali J AJ Bhanot Anisha A Wu Christine J CJ Hibert Matthew L ML Kim Minhae M Mahmood Umar U Stufflebeam Steven M SM Schroeder Frederick A FA Wang Changning C Roffman Joshua L JL Holt Daphne J DJ Greve Douglas N DN Pasternak Ofer O Kubicki Marek M Wey Hsiao-Ying HY Hooker Jacob M JM

Nature communications 20190703 1

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 [<sup>11</sup>C]Martinostat positron emission tomography (PET) neuroimaging (n = 41). Relative HDAC expression increases with age in cerebral white matter, and ...[more]

PMID: 31270332

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Dataset Information

Neuroepigenetic signatures of age and sex in the living human brain.

Publications

Neuroepigenetic signatures of age and sex in the living human brain.

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