Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice
Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice
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DOI：
10.1126/science.1186088
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发表时间：
2010-05-07
期刊：
影响因子：
56.9
通讯作者：
Fischer, Andre
中科院分区：
文献类型：
--
作者：
Peleg, Shahaf;Sananbenesi, Farahnaz;Fischer, Andre
随着人类寿命的延长，患有认知能力下降的人数急剧增加。然而，与年龄相关的记忆障碍的机制还不清楚。在这里，我们表明，记忆障碍在老化的大脑中的小鼠与海马染色质可塑性改变。在学习过程中，老年小鼠表现出组蛋白H4赖氨酸12（H4 K12）乙酰化的特异性失调，并且未能启动与记忆巩固相关的海马基因表达程序。生理H4 K12乙酰化的恢复恢复了学习诱导基因的表达，并导致认知能力的恢复。我们的数据表明，去调节H4 K12乙酰化可能是衰老小鼠大脑中基因组-环境相互作用受损的早期生物标志物。
As the human life span increases, the number of people suffering from cognitive decline is rising dramatically. The mechanisms underlying age-associated memory impairment are, however, not understood. Here we show that memory disturbances in the aging brain of the mouse are associated with altered hippocampal chromatin plasticity. During learning, aged mice display a specific deregulation of histone H4 lysine 12 (H4K12) acetylation and fail to initiate a hippocampal gene expression program associated with memory consolidation. Restoration of physiological H4K12 acetylation reinstates the expression of learning-induced genes and leads to the recovery of cognitive abilities. Our data suggest that deregulated H4K12 acetylation may represent an early biomarker of an impaired genome-environment interaction in the aging mouse brain.