Neuroepigenetic signatures of age and sex in the living human brain
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 [ 11 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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- 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. doi: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 = {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 [ 11 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.},
doi = {10.1038/s41467-019-11031-0},
journal = {Nature Communications},
number = 1,
volume = 10,
place = {United Kingdom},
year = {2019},
month = {7}
}
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