Neuroepigenetic Signatures of Age and Sex in the Living Human Brain


Gilbert TM, Zürcher NR, Catanese MC, Tseng C-EJ, Di Biase MA, Lyall AE, Hightower BG, Parmar AJ, Bhanot A, Wu CJ, et al. Neuroepigenetic Signatures of Age and Sex in the Living Human Brain. Nat Commun. 2019;10 (1) :2945.

Date Published:

2019 Jul 03


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 [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.

Last updated on 10/28/2019