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Neuroepigenetic signatures of age and sex in the living human brain

Author

Listed:
  • 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
    Massachusetts General 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
    Massachusetts General Hospital, Harvard Medical School)

  • Daphne J. Holt

    (Massachusetts General Hospital, Harvard Medical School
    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
    Massachusetts General Hospital, Harvard Medical School)

  • Hsiao-Ying Wey

    (Massachusetts General Hospital, Harvard Medical School)

  • Jacob M. Hooker

    (Massachusetts General Hospital, Harvard Medical School)

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.

Suggested Citation

  • 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., 2019. "Neuroepigenetic signatures of age and sex in the living human brain," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11031-0
    DOI: 10.1038/s41467-019-11031-0
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