Role of Epigenetics in Age-Related Long-Term Memory Loss
The epigenetic mechanisms of DNA methylation and histone modifications have been shown to play a vital role in long-term memory formation by regulating the expression of genes involved in memory processes. In fear conditioned mice, CpG islands in the promoter regions of the memory-linked genes, reelin and Protein Phosphatase 1 (PP1), undergo either hypomethylation (reelin) or hypermethylation (PP1). By altering the expression of these genes, epigenetic mechanisms can affect the ability to form long-term memories. The pivotal role of histone modifications in long-term potentiation is made evident by such genetic disorders as Rubenstein-Taybi syndrome (RTS), a disease characterized in part by cognitive dysfunction. The histone acetyl transferase domain of CREB-binding protein is catalytically inert in RTS patients and is believed to be the cause of a limited ability for memory formation. The role of epigenetics in age-related memory loss is best seen by studying the classic age-related disease, Alzheimer’s disease (AD), which is characterized by severe memory loss. Biological aging correlates with a loss of expression and activity of certain epigenetic modulating enzymes, such as DNA methyltransferase1. The loss of maintenance of the epigenome is believed to be key to understanding the role of epigenetics in age-related cognitive diseases, such as AD.
KeywordsDNA methylation Histone modifications Long-term potentiation Rubenstein–Taybi syndrome Reelin PP1 Alzheimer’s disease
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