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Title: 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.

Authors:
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Publication Date:
Research Org.:
Massachusetts General Hospital, Boston, MA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institute on Drug Abuse; National Institute of Mental Health; American Federation for Aging Research (AFAR)
OSTI Identifier:
1619532
Alternate Identifier(s):
OSTI ID: 1611049
Grant/Contract Number:  
SC0008430
Resource Type:
Published Article
Journal Name:
Nature Communications
Additional Journal Information:
Journal Name: Nature Communications Journal Volume: 10 Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United Kingdom
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Science & Technology - Other Topics

Citation Formats

Gilbert, Tonya M., Zürcher, Nicole R., Catanese, Mary C., Tseng, Chieh-En J., Di Biase, Maria A., Lyall, Amanda E., Hightower, Baileigh G., Parmar, Anjali J., Bhanot, Anisha, Wu, Christine J., Hibert, Matthew L., Kim, Minhae, Mahmood, Umar, Stufflebeam, Steven M., Schroeder, Frederick A., Wang, Changning, Roffman, Joshua L., Holt, Daphne J., Greve, Douglas N., Pasternak, Ofer, Kubicki, Marek, Wey, Hsiao-Ying, and Hooker, Jacob M. Neuroepigenetic signatures of age and sex in the living human brain. United Kingdom: N. p., 2019. Web. https://doi.org/10.1038/s41467-019-11031-0.
Gilbert, Tonya M., Zürcher, Nicole R., Catanese, Mary C., Tseng, Chieh-En J., Di Biase, Maria A., Lyall, Amanda E., Hightower, Baileigh G., Parmar, Anjali J., Bhanot, Anisha, Wu, Christine J., Hibert, Matthew L., Kim, Minhae, Mahmood, Umar, Stufflebeam, Steven M., Schroeder, Frederick A., Wang, Changning, Roffman, Joshua L., Holt, Daphne J., Greve, Douglas N., Pasternak, Ofer, Kubicki, Marek, Wey, Hsiao-Ying, & Hooker, Jacob M. Neuroepigenetic signatures of age and sex in the living human brain. United Kingdom. https://doi.org/10.1038/s41467-019-11031-0
Gilbert, Tonya M., Zürcher, Nicole R., Catanese, Mary C., Tseng, Chieh-En J., Di Biase, Maria A., Lyall, Amanda E., Hightower, Baileigh G., Parmar, Anjali J., Bhanot, Anisha, Wu, Christine J., Hibert, Matthew L., Kim, Minhae, Mahmood, Umar, Stufflebeam, Steven M., Schroeder, Frederick A., Wang, Changning, Roffman, Joshua L., Holt, Daphne J., Greve, Douglas N., Pasternak, Ofer, Kubicki, Marek, Wey, Hsiao-Ying, and Hooker, Jacob M. Wed . "Neuroepigenetic signatures of age and sex in the living human brain". United Kingdom. https://doi.org/10.1038/s41467-019-11031-0.
@article{osti_1619532,
title = {Neuroepigenetic signatures of age and sex in the living human brain},
author = {Gilbert, Tonya M. and Zürcher, Nicole R. and Catanese, Mary C. and Tseng, Chieh-En J. and Di Biase, Maria A. and Lyall, Amanda E. and Hightower, Baileigh G. and Parmar, Anjali J. and Bhanot, Anisha and Wu, Christine J. and Hibert, Matthew L. and Kim, Minhae and Mahmood, Umar and Stufflebeam, Steven M. and Schroeder, Frederick A. and Wang, Changning and Roffman, Joshua L. and Holt, Daphne J. and Greve, Douglas N. and Pasternak, Ofer and Kubicki, Marek and Wey, Hsiao-Ying and Hooker, Jacob M.},
abstractNote = {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.},
doi = {10.1038/s41467-019-11031-0},
journal = {Nature Communications},
number = 1,
volume = 10,
place = {United Kingdom},
year = {2019},
month = {7}
}

Journal Article:
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https://doi.org/10.1038/s41467-019-11031-0

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Cited by: 11 works
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