原创力文档age-related memory impairment is associated with disrupted multivariate epigenetic coordination in the hippocampus与年龄相关的记忆障碍与中断相关多元在海马体中表观遗传协调.pdfVIP
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age-related memory impairment is associated with disrupted multivariate epigenetic coordination in the hippocampus与年龄相关的记忆障碍与中断相关多元在海马体中表观遗传协调
Age-Related Memory Impairment Is Associated with
Disrupted Multivariate Epigenetic Coordination in the
Hippocampus
1,2. 1. 1 1 3
James F. Castellano , Bonnie R. Fletcher , Bennett Kelley-Bell , David H. Kim , Michela Gallagher ,
Peter R. Rapp1*
1 Laboratory of Experimental Gerontology, National Institute on Aging, Baltimore, Maryland, United States of America, 2 Graduate Program in Neuroscience, Mount Sinai
School of Medicine, New York, New York, United States of America, 3 Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, Maryland,
United States of America
Abstract
Mounting evidence linking epigenetic regulation to memory-related synaptic plasticity raises the possibility that altered
chromatin modification dynamics might contribute to age-dependent cognitive decline. Here we show that the
coordinated orchestration of both baseline and experience-dependent epigenetic regulation seen in the young adult
hippocampus is lost in association with cognitive aging. Using a well-characterized rat model that reliably distinguishes
aged individuals with significant memory impairment from others with normal memory, no single epigenetic mark or
experience-dependent modification in the hippocampus uniquely predicted differences in the cognitive outcome of aging.
The results instead point to a multivariate pattern in which modification-specific, bidirectional chromatin regulation is
dependent on recent behavioral experience, chronological age, cognitive status, and hippocampal region. Whereas many
epigenetic signatures were coupled with memory capacity among young adults and aged rats with
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