Neuroepigenetic signatures of age and sex in the living human brain

Tonya M. Gilbert, Nicole R. Zürcher, Mary C. Catanese, Chieh-En J. Tseng, Maria A. 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 and Jacob M. Hooker ()
Additional contact information
Tonya M. Gilbert: Massachusetts General Hospital, Harvard Medical School
Nicole R. Zürcher: Massachusetts General Hospital, Harvard Medical School
Mary C. Catanese: Massachusetts General Hospital, Harvard Medical School
Chieh-En J. Tseng: Massachusetts General Hospital, Harvard Medical School
Maria A. Biase: Brigham and Women’s Hospital, Harvard Medical School
Amanda E. Lyall: Brigham and Women’s Hospital, Harvard Medical School
Baileigh G. Hightower: Massachusetts General Hospital, Harvard Medical School
Anjali J. Parmar: Massachusetts General Hospital, Harvard Medical School
Anisha Bhanot: Massachusetts General Hospital, Harvard Medical School
Christine J. Wu: Massachusetts General Hospital, Harvard Medical School
Matthew L. Hibert: Massachusetts General Hospital, Harvard Medical School
Minhae Kim: Massachusetts General Hospital, Harvard Medical School
Umar Mahmood: Massachusetts General Hospital, Harvard Medical School
Steven M. Stufflebeam: Massachusetts General Hospital, Harvard Medical School
Frederick A. Schroeder: Massachusetts General Hospital, Harvard Medical School
Changning Wang: Massachusetts General Hospital, Harvard Medical School
Joshua L. Roffman: Massachusetts General Hospital, Harvard Medical School
Daphne J. Holt: Massachusetts General Hospital, Harvard Medical School
Douglas N. Greve: Massachusetts General Hospital, Harvard Medical School
Ofer Pasternak: Brigham and Women’s Hospital, Harvard Medical School
Marek Kubicki: Brigham and Women’s Hospital, Harvard Medical School
Hsiao-Ying Wey: Massachusetts General Hospital, Harvard Medical School
Jacob M. Hooker: Massachusetts General Hospital, Harvard Medical School

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11031-0

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