Altered histone acetylation is associated with age-dependent memory impairment in mice.
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.
Peleg
Shahaf
S
Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute, Grisebach Str. 5, D-37077 Goettingen, Germany.
Sananbenesi
Farahnaz
F
Zovoilis
Athanasios
A
Burkhardt
Susanne
S
Bahari-Javan
Sanaz
S
Agis-Balboa
Roberto Carlos
RC
Cota
Perla
P
Wittnam
Jessica Lee
JL
Gogol-Doering
Andreas
A
Opitz
Lennart
L
Salinas-Riester
Gabriella
G
Dettenhofer
Markus
M
Kang
Hui
H
Farinelli
Laurent
L
Chen
Wei
W
Fischer
André
A
D000107:Acetylation; D000375:Aging / Q000235:genetics*; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D003213:Conditioning, Psychological; D044127:Epigenesis, Genetic; D005239:Fear; D000080865:Formins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D007858:Learning / Q000187:drug effects; D008239:Lysine / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D015854:Up-Regulation
D002843:Chromatin; D000080865:Formins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C549436:formin 2 protein, mouse; C528828:suberoyl bis-hydroxamic acid; D008239:Lysine