一項(xiàng)對(duì)進(jìn)入暮年的小鼠的研究發(fā)現(xiàn)了在其腦中的損害其學(xué)習(xí)能力的特異性的變化,，研究人員說(shuō),，他們的發(fā)現(xiàn)可能在未來(lái)給那些有與年齡有關(guān)的記憶損害的人帶來(lái)好處,。這一發(fā)現(xiàn)可能會(huì)特別重要,，因?yàn)檫@種與年齡有關(guān)的損害隨著人類平均壽命的增加而變得日益常見,。
Shahaf Peleg及其同僚首先讓3個(gè)月大,、8個(gè)月大及16個(gè)月大的小鼠從事不同的學(xué)習(xí)任務(wù),，以期決定在什么時(shí)候會(huì)開始發(fā)生與年齡有關(guān)的認(rèn)知損害,。在發(fā)現(xiàn)16個(gè)月大的小鼠的學(xué)習(xí)速度最慢以后，研究人員對(duì)在它們腦中的基因表達(dá)進(jìn)行了研究,。他們發(fā)現(xiàn),，這些老年小鼠的包裹基因組的蛋白質(zhì)修飾了發(fā)生變化,，特別是組蛋白H4K12的乙酰化的改變,。Peleg及其同僚接著對(duì)這一H4K12乙?；恼系K是如何影響老年小鼠的基因表達(dá)進(jìn)行了調(diào)查。他們發(fā)現(xiàn),，16個(gè)月大的小鼠的與學(xué)習(xí)和記憶有關(guān)的基因表達(dá)的調(diào)節(jié)受到了嚴(yán)重的損害,，而這些小鼠無(wú)法利用那些與年輕小鼠所依賴的相同的關(guān)鍵性的信號(hào)傳導(dǎo)通路。 然而,，當(dāng)這些16個(gè)月大的小鼠的H4K12乙?；匦禄謴?fù)而相關(guān)的學(xué)習(xí)基因被表達(dá)之后，其學(xué)習(xí)和儲(chǔ)存記憶的能力可再次恢復(fù)成像年輕小鼠一樣,。
這一發(fā)現(xiàn)提示,，隨著時(shí)間的推移，我們的基因組表達(dá)方式的改變可在我們變老的時(shí)候損害我們的學(xué)習(xí)能力,，而H4K12乙?；恼{(diào)節(jié)的突然解除可被看作是認(rèn)知能力下降的一個(gè)早期的警示信號(hào)。在一篇Perspective中,，J. David Sweatt對(duì)這一研究進(jìn)行了更為詳細(xì)的描述,。（生物谷Bioon.com）
生物谷推薦原文出處1：
Science DOI: 10.1126/science.1186088
Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice
Shahaf Peleg,1,* Farahnaz Sananbenesi,1,* Athanasios Zovoilis,1,* Susanne Burkhardt,1 Sanaz Bahari-Javan,1 Roberto Carlos Agis-Balboa,1 Perla Cota,1 Jessica Lee Wittnam,1,Andreas Gogol-Doering,2 Lennart Opitz,3 Gabriella Salinas-Riester,3 Markus Dettenhofer,4 Hui Kang,2 Laurent Farinelli,5 Wei Chen,2 André Fischer1,
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.
1 Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute, Grisebach Str. 5, D-37077 Goettingen, Germany.
2 Max Delbrueck Center for Molecular Medicine, Institute for Medical Systems Biology, Robert-R?ssle-Strasse 10, D-13125 Berlin-Buch, Germany.
3 DNA Microarray Facility, Georg August University, Humboldtallee 23, D-37073 Goettingen, Germany.
4 Harvard Medical School, Genetics Department, 77 Ave Louis Pasteur, Boston, MA 02115, USA.
5 Fasteris SA, CH-1228 Plan-les-Ouates, Switzerland.
生物谷推薦原文出處2：
Science DOI: 10.1126/science.1189968
NEUROSCIENCE:Epigenetics and Cognitive Aging
J. David Sweatt
Cognitive decline, especially in memory capacity, is a normal part of aging (1). Indeed, the painful reality is that aging-related cognitive decline likely begins when one is in their late 40s. This deterioration is particularly pronounced in declarative memory—the ability to recall facts and experiences—and has been associated with aberrant changes in gene expression in the brain's hippocampus and frontal lobe. However, the molecular mechanisms underlying these changes in gene regulation are not currently known (2, 3). On page 753 of this issue, Peleg et al. (4) bolster an emerging hypothesis that changes in the epigenetic modification of chromatin in the adult central nervous system drive cognitive decline.
Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
