Epigenetic Mechanisms of Learning and Memory: Implications for Aging

Creighton, Samantha D.; Stefanelli, Gilda; Reda, Anas; Zovkic, Iva B.

doi:10.3390/ijms21186918

Cited by 23 publications

(20 citation statements)

References 229 publications

(420 reference statements)

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“…Histone lysine acetylation levels change with aging and comprehensive reviews have been published describing these changes and anti-aging dietary interventions [ 142 , 143 ], including those that occur specifically in aging brain [ 144 ]. In rodent brain, bulk histone H4 acetylation was shown to decrease with aging in Sprague-Dawley rat cortex [ 145 ] or Wistar rat hippocampus [ 146 ], but increase with aging in Long-Evans rat hippocampus [ 147 ].…”

Section: Brain Histone Acetylation Changes With Agingmentioning

confidence: 99%

Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan

Bradshaw

2021

Antioxidants

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Acetyl-CoA is a metabolite at the crossroads of central metabolism and the substrate of histone acetyltransferases regulating gene expression. In many tissues fasting or lifespan extending calorie restriction (CR) decreases glucose-derived metabolic flux through ATP-citrate lyase (ACLY) to reduce cytoplasmic acetyl-CoA levels to decrease activity of the p300 histone acetyltransferase (HAT) stimulating pro-longevity autophagy. Because of this, compounds that decrease cytoplasmic acetyl-CoA have been described as CR mimetics. But few authors have highlighted the potential longevity promoting roles of nuclear acetyl-CoA. For example, increasing nuclear acetyl-CoA levels increases histone acetylation and administration of class I histone deacetylase (HDAC) inhibitors increases longevity through increased histone acetylation. Therefore, increased nuclear acetyl-CoA likely plays an important role in promoting longevity. Although cytoplasmic acetyl-CoA synthetase 2 (ACSS2) promotes aging by decreasing autophagy in some peripheral tissues, increased glial AMPK activity or neuronal differentiation can stimulate ACSS2 nuclear translocation and chromatin association. ACSS2 nuclear translocation can result in increased activity of CREB binding protein (CBP), p300/CBP-associated factor (PCAF), and other HATs to increase histone acetylation on the promoter of neuroprotective genes including transcription factor EB (TFEB) target genes resulting in increased lysosomal biogenesis and autophagy. Much of what is known regarding acetyl-CoA metabolism and aging has come from pioneering studies with yeast, fruit flies, and nematodes. These studies have identified evolutionary conserved roles for histone acetylation in promoting longevity. Future studies should focus on the role of nuclear acetyl-CoA and histone acetylation in the control of hypothalamic inflammation, an important driver of organismal aging.

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Section: Brain Histone Acetylation Changes With Agingmentioning

confidence: 99%

Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan

Bradshaw

2021

Antioxidants

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“…Over the last decade, a number of studies have begun to explore how the brain epigenome changes across the lifespan and contributes to age-related memory decline, a significant risk factor for the development of Alzheimer's disease and related dementias. As an excellent recent review has been published on this topic [5], we will briefly summarize some of the significant findings from the last decade.…”

Section: Epigenetics In Age-related Memory Declinementioning

confidence: 99%

“…Outside of its role in cell differentiation during development, there is mounting evidence suggesting that epigenetic mechanisms play a significant role in transcriptional control during memory formation in the brain [3,4]. Importantly, age-related changes in these mechanisms have been strongly implicated with memory loss across the lifespan [5]. Additionally, dysregulation of epigenetic mechanisms has been widely implicated in various disease states, ranging from cancers to numerous neurological, psychiatric, and neurodegenerative disorders [6].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer’s Disease

Maity

Farrell

Navabpour

et al. 2021

IJMS

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Epigenetic mechanisms, which include DNA methylation, a variety of post-translational modifications of histone proteins (acetylation, phosphorylation, methylation, ubiquitination, sumoylation, serotonylation, dopaminylation), chromatin remodeling enzymes, and long non-coding RNAs, are robust regulators of activity-dependent changes in gene transcription. In the brain, many of these epigenetic modifications have been widely implicated in synaptic plasticity and memory formation. Dysregulation of epigenetic mechanisms has been reported in the aged brain and is associated with or contributes to memory decline across the lifespan. Furthermore, alterations in the epigenome have been reported in neurodegenerative disorders, including Alzheimer’s disease. Here, we review the diverse types of epigenetic modifications and their role in activity- and learning-dependent synaptic plasticity. We then discuss how these mechanisms become dysregulated across the lifespan and contribute to memory loss with age and in Alzheimer’s disease. Collectively, the evidence reviewed here strongly supports a role for diverse epigenetic mechanisms in memory formation, aging, and neurodegeneration in the brain.

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“…The concept of CIMP was first introduced by Toyota et al in 1999 and defined as widespread methylation in the CpG island of the genes [ 4 ]. The methylation process was described by the addition of the methyl group (CH 3 − ) at the carbon 5 of the cytosine ring to form 5-methylcytosine, and the process is catalysed by the enzyme DNA methyltransferase (DNMT) in which S-adenosyl-methionine (SAM) acts as a methyl donor [ 5 , 6 ]. Aberrant methylation in CRC has correlated with the inactivation of tumour suppressor genes [ 7 ] and the activation of oncogenes [ 8 ] that function to control a variety of cellular processes, including apoptosis, proliferation, invasion, and migration [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

Baharudin

Ishak

Yusof³

et al. 2022

Diagnostics

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The aims were to profile the DNA methylation in colorectal cancer (CRC) and to explore cancer-specific methylation biomarkers. Fifty-four pairs of CRCs and the adjacent normal tissues were subjected to Infinium Human Methylation 450K assay and analysed using ChAMP R package. A total of 26,093 differentially methylated probes were identified, which represent 6156 genes; 650 probes were hypermethylated, and 25,443 were hypomethylated. Hypermethylated sites were common in CpG islands, while hypomethylated sites were in open sea. Most of the hypermethylated genes were associated with pathways in cancer, while the hypomethylated genes were involved in the PI3K-AKT signalling pathway. Among the identified differentially methylated probes, we found evidence of four potential probes in CRCs versus adjacent normal; HOXA2 cg06786372, OPLAH cg17301223, cg15638338, and TRIM31 cg02583465 that could serve as a new biomarker in CRC since these probes were aberrantly methylated in CRC as well as involved in the progression of CRC. Furthermore, we revealed the potential of promoter methylation ADHFE1 cg18065361 in differentiating the CRC from normal colonic tissue from the integrated analysis. In conclusion, aberrant DNA methylation is significantly involved in CRC pathogenesis and is associated with gene silencing. This study reports several potential important methylated genes in CRC and, therefore, merit further validation as novel candidate biomarker genes in CRC.

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Epigenetic Mechanisms of Learning and Memory: Implications for Aging

Cited by 23 publications

References 229 publications

Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan

Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan

Epigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer’s Disease

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

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