Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02215, USA.
Nat Commun. 2019 Jul 3;10(1):2945. doi: 10.1038/s41467-019-11031-0.
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.
已经证明，基因转录存在与年龄和性别相关的改变，但潜在机制尚未解决。神经表观遗传途径调节大脑中的基因转录。在这里，我们使用 [C]Martinostat 正电子发射断层扫描 (PET) 神经影像学（n=41）测量健康人类衰老过程中和性别之间的表观遗传酶，组蛋白去乙酰化酶 (HDACs) 的体内表达。相对 HDAC 表达在大脑白质中随年龄增长而增加，并与白质微观结构的年龄相关破坏相关。一项尸体研究证实，老年供体的白质组织中 HDAC1 和 HDAC2 同工酶升高。与情绪和记忆相关的大脑区域也存在特定于性别的体内 HDAC 表达差异，包括杏仁核和海马体。海马体和白质的 HDAC 表达与情绪调节技能呈负相关（n=23）。年龄和性别与体内的 HDAC 表达相关，这可能会导致与年龄和性别相关的转录变化，并影响人类行为。
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