scholarly journals Age-related disturbances in DNA (hydroxy)methylation in APP/PS1 mice

2018 ◽  
Vol 9 (1) ◽  
pp. 190-202 ◽  
Author(s):  
Leonidas Chouliaras ◽  
Roy Lardenoije ◽  
Gunter Kenis ◽  
Diego Mastroeni ◽  
Patrick R. Hof ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Dna Methylation ◽  
Brain Aging ◽  
Wild Type ◽  
Dna Hydroxymethylation ◽  
Quantitative Immunohistochemistry ◽  
Age Related ◽  
Aberrant Dna Methylation ◽  
Methylation Patterns ◽  
Age Related Changes

Abstract Brain aging has been associated with aberrant DNA methylation patterns, and changes in the levels of DNA methylation and associated markers have been observed in the brains of Alzheimer’s disease (AD) patients. DNA hydroxymethylation, however, has been sparsely investigated in aging and AD. We have previously reported robust decreases in 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in the hippocampus of AD patients compared to non-demented controls. In the present study, we investigated 3- and 9-month-old APPswe/PS1ΔE9 transgenic and wild-type mice for possible age-related alterations in 5-mC and 5-hmC levels in three hippocampal sub-regions using quantitative immunohistochemistry. While age-related increases in levels of both 5-mC and 5-hmC were found in wild-type mice, APPswe/PS1ΔE9 mice showed decreased levels of 5-mC at 9 months of age and no age-related changes in 5-hmC throughout the hippocampus. Altogether, these findings suggest that aberrant amyloid processing impact on the balance between DNA methylation and hydroxymethylation in the hippocampus during aging in mice.

scholarly journals Early life DNA methylation profiles are indicative of age-related transcriptome changes

2019 ◽  
Author(s):  
Niran Hadad ◽  
Dustin R. Masser ◽  
Laura Blanco-Berdugo ◽  
David R. Stanford ◽  
Willard M. Freeman
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Functional Outcomes ◽  
Brain Aging ◽  
Epigenetic Modification ◽  
Integrated Analysis ◽  
Epigenetic Variability ◽  
Age Related ◽  
Developmental Origins Of Disease ◽  
Methylation Patterns

AbstractAlterations to cellular and molecular programs with brain aging result in cognitive impairment and susceptibility to neurodegenerative disease. Changes in DNA methylation patterns, an epigenetic modification required for various CNS functions, are observed with aging and can be prevented by anti-aging interventions, but the functional outcomes of altered methylation on transcriptome profiles are poorly understood with brain aging. Integrated analysis of the hippocampal methylome and transcriptome with aging of male and female mice demonstrates that age-related differences in methylation and gene expression are anti-correlated within gene bodies and enhancers, but not promoters. Methylation levels at young age of genes altered with aging are positively associated with age-related expression changes even in the absence of significant changes to methylation with aging, a finding also observed in mouse Alzheimer’s models. DNA methylation patterns established in youth, in combination with other epigenetic marks, are able to predict changes in transcript trajectories with aging. These findings are consistent with the developmental origins of disease hypothesis and indicate that epigenetic variability in early life may explain differences in age-related disease.

scholarly journals Early-life DNA methylation profiles are indicative of age-related transcriptome changes

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Niran Hadad ◽  
Dustin R. Masser ◽  
Laura Blanco-Berdugo ◽  
David R. Stanford ◽  
Willard M. Freeman
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Early Life ◽  
Brain Aging ◽  
Epigenetic Modification ◽  
Age Related ◽  
Developmental Origins Of Disease ◽  
Altered Gene ◽  
Methylation Patterns ◽  
Relationship Of

Abstract Background Alterations to cellular and molecular programs with brain aging result in cognitive impairment and susceptibility to neurodegenerative disease. Changes in DNA methylation patterns, an epigenetic modification required for various CNS functions are observed with brain aging and can be prevented by anti-aging interventions, but the relationship of altered methylation to gene expression is poorly understood. Results Paired analysis of the hippocampal methylome and transcriptome with aging of male and female mice demonstrates that age-related differences in methylation and gene expression are anti-correlated within gene bodies and enhancers. Altered promoter methylation with aging was found to be generally un-related to altered gene expression. A more striking relationship was found between methylation levels at young age and differential gene expression with aging. Highly methylated gene bodies and promoters in early life were associated with age-related increases in gene expression even in the absence of significant methylation changes with aging. As well, low levels of methylation in early life were correlated to decreased expression with aging. This relationship was also observed in genes altered in two mouse Alzheimer’s models. Conclusion DNA methylation patterns established in youth, in combination with other epigenetic marks, were able to accurately predict changes in transcript trajectories with aging. These findings are consistent with the developmental origins of disease hypothesis and indicate that epigenetic variability in early life may explain differences in aging trajectories and age-related disease.

P1-192: Aβ-POTENTIATED AND Aβ-INDEPENDENT AGE RELATED CHANGES IN THE LENS OF THE EYE IN WILD-TYPE AND ALZHEIMER'S DISEASE MICE

2006 ◽  
Vol 14 (7S_Part_6) ◽  
pp. P352-P352
Author(s):  
Juliet A. Moncaster ◽  
Mark W. Wojnarowicz ◽  
Rebecca Zeng ◽  
Olga Minaeva ◽  
Lee Goldstein
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Wild Type ◽  
Age Related ◽  
Age Related Changes

[P1-184]: Aβ-INDEPENDENT AND Aβ-POTENTIATED AGE-RELATED CHANGES IN THE LENS OF WILD-TYPE AND ALZHEIMER's DISEASE TG2576 MICE

2017 ◽  
Vol 13 (7S_Part_6) ◽  
pp. P312-P313
Author(s):  
Juliet A. Moncaster ◽  
Mark W. Wojnarowicz ◽  
Olga Minaeva ◽  
Srikant Sarangi ◽  
Zoe Brasher ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Wild Type ◽  
Age Related ◽  
Tg2576 Mice ◽  
Age Related Changes

scholarly journals Postnatal development- and age-related changes in DNA-methylation patterns in the human genome

2012 ◽  
Vol 40 (14) ◽  
pp. 6477-6494 ◽  
Author(s):  
Paraskevi Salpea ◽  
Valya R. Russanova ◽  
Tazuko H. Hirai ◽  
Thomae G. Sourlingas ◽  
Kalliope E. Sekeri-Pataryas ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Postnatal Development ◽  
Age Related ◽  
Methylation Patterns ◽  
Age Related Changes

scholarly journals DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Vanessa Lakis ◽  
◽  
Rita T. Lawlor ◽  
Felicity Newell ◽  
Ann-Marie Patch ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Neuroendocrine Tumors ◽  
Methylation Profile ◽  
Pancreatic Neuroendocrine Tumors ◽  
Wild Type ◽  
Genomic Information ◽  
Chromosome 11 ◽  
Dna Methylation Profile ◽  
Methylation Patterns ◽  
Recurrent Patterns

AbstractHere we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.

White Adipose Tissue Depots in GHR−/− Mice: Age-Related Changes in Comparison to Wild-Type Controls

2011 ◽  
pp. P2-351-P2-351
Author(s):  
Lucila Sackmann Sala ◽  
Clare B Vesel ◽  
Ellen R Lubbers ◽  
Rachel D Munn ◽  
Katie M Troike ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Wild Type ◽  
Adipose Tissue Depots ◽  
Age Related ◽  
Age Related Changes

Dysregulation of schizophrenia-associated genes and genome-wide hypomethylation in neurons overexpressing DNMT1

Epigenomics ◽  
2021 ◽  
Author(s):  
Sonal Saxena ◽  
Sumana Choudhury ◽  
Pranay Amruth Maroju ◽  
Anuhya Anne ◽  
Lov Kumar ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Copy Number ◽  
Embryonic Stem ◽  
Wild Type ◽  
Independent Manner ◽  
Transcript Levels ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Increased Activity

Aim: To study the effects of DNMT1 overexpression on transcript levels of genes dysregulated in schizophrenia and on genome-wide methylation patterns. Materials & methods: Transcriptome and DNA methylome comparisons were made between R1 (wild-type) and Dnmt1tet/tet mouse embryonic stem cells and neurons overexpressing DNMT1. Genes dysregulated in both Dnmt1tet/tet cells and schizophrenia patients were studied further. Results & conclusions: About 50% of dysregulated genes in patients also showed altered transcript levels in Tet/Tet neurons in a DNA methylation-independent manner. These neurons unexpectedly showed genome-wide hypomethylation, increased transcript levels of Tet1 and Apobec 1-3 genes and increased activity and copy number of LINE-1 elements. The observed similarities between Tet/Tet neurons and schizophrenia brain samples reinforce DNMT1 overexpression as a risk factor.

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