Neuroepigenetic signatures of age and sex in the living human brain

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.

doi:10.1038/s41467-019-11031-0

Title: Neuroepigenetic signatures of age and sex in the living human brain

Journal Article · Wed Jul 03 00:00:00 EDT 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-11031-0· OSTI ID:1619532

Gilbert, Tonya M.;

; Catanese, Mary C.;

; Di Biase, Maria A.;

; Hightower, Baileigh G.; Parmar, Anjali J.; Bhanot, Anisha;

; Hibert, Matthew L.;

; Mahmood, Umar;

; Schroeder, Frederick A.; Wang, Changning; Roffman, Joshua L.; Holt, Daphne J.; Greve, Douglas N.; Pasternak, Ofer more »

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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Research Organization:: Massachusetts General Hospital, Boston, MA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institute on Drug Abuse; National Institute of Mental Health; American Federation for Aging Research (AFAR)

Grant/Contract Number:: SC0008430

OSTI ID:: 1619532

Alternate ID(s):: OSTI ID: 1611049

Journal Information:: Nature Communications, Journal Name: Nature Communications Vol. 10 Journal Issue: 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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Cited by: 30 works

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