scholarly journals Distinct DNA methylation targets by aging and chronic inflammation: a pilot study using gastric mucosa infected with Helicobacter pylori

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Satoshi Yamashita ◽  
Sohachi Nanjo ◽  
Emil Rehnberg ◽  
Naoko Iida ◽  
Hideyuki Takeshima ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Chronic Inflammation ◽  
Cpg Islands ◽  
Human Gastric Mucosa ◽  
Driver Genes ◽  
Age Related ◽  
A Genome ◽  
Aberrant Dna Methylation

Abstract Background Aberrant DNA methylation is induced by aging and chronic inflammation in normal tissues. The induction by inflammation is widely recognized as acceleration of age-related methylation. However, few studies addressed target genomic regions and the responsible factors in a genome-wide manner. Here, we analyzed methylation targets by aging and inflammation, taking advantage of the potent methylation induction in human gastric mucosa by Helicobacter pylori infection-triggered inflammation. Results DNA methylation microarray analysis of 482,421 CpG probes, grouped into 270,249 genomic blocks, revealed that high levels of methylation were induced in 44,461 (16.5%) genomic blocks by inflammation, even after correction of the influence of leukocyte infiltration. A total of 61.8% of the hypermethylation was acceleration of age-related methylation while 21.6% was specific to inflammation. Regions with H3K27me3 were frequently hypermethylated both by aging and inflammation. Basal methylation levels were essential for age-related hypermethylation while even regions with little basal methylation were hypermethylated by inflammation. When limited to promoter CpG islands, being a microRNA gene and high basal methylation levels strongly enhanced hypermethylation while H3K27me3 strongly enhanced inflammation-induced hypermethylation. Inflammation was capable of overriding active transcription. In young gastric mucosae, genes with high expression and frequent mutations in gastric cancers were more frequently methylated than in old ones. Conclusions Methylation by inflammation was not simple acceleration of age-related methylation. Targets of aberrant DNA methylation were different between young and old gastric mucosae, and driver genes were preferentially methylated in young gastric mucosa.

scholarly journals The effect of age on DNA methylation in whole blood among Bangladeshi men and women

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Rick J. Jansen ◽  
Lin Tong ◽  
Maria Argos ◽  
Farzana Jasmine ◽  
Muhammad Rakibuz-Zaman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Whole Blood ◽  
Cpg Islands ◽  
Chronological Age ◽  
Cpg Sites ◽  
Age Related ◽  
Genome Wide ◽  
A Genome ◽  
Effect Of Age ◽  
Age Related Changes

Abstract Background It is well-known that methylation changes occur as humans age, however, understanding how age-related changes in DNA methylation vary by sex is lacking. In this study, we characterize the effect of age on DNA methylation in a sex-specific manner and determine if these effects vary by genomic context. We used the Illumina HumanMethylation 450 K array and DNA derived from whole blood for 400 adult participants (189 males and 211 females) from Bangladesh to identify age-associated CpG sites and regions and characterize the location of these age-associated sites with respect to CpG islands (vs. shore, shelf, or open sea) and gene regions (vs. intergenic). We conducted a genome-wide search for age-associated CpG sites (among 423,604 sites) using a reference-free approach to adjust for cell type composition (the R package RefFreeEWAS) and performed an independent replication analysis of age-associated CpGs. Results The number of age-associated CpGs (p < 5 x 10− 8) were 986 among men and 3479 among women of which 2027(63.8%) and 572 (64.1%) replicated (using Bonferroni adjusted p < 1.2 × 10− 5). For both sexes, age-associated CpG sites were more likely to be hyper-methylated with increasing age (compared to hypo-methylated) and were enriched in CpG islands and promoter regions compared with other locations and all CpGs on the array. Although we observed strong correlation between chronological age and previously-developed epigenetic age models (r ≈ 0.8), among our top (based on lowest p-value) age-associated CpG sites only 12 for males and 44 for females are included in these prediction models, and the median chronological age compared to predicted age was 44 vs. 51.7 in males and 45 vs. 52.1 in females. Conclusions Our results describe genome-wide features of age-related changes in DNA methylation. The observed associations between age and methylation were generally consistent for both sexes, although the associations tended to be stronger among women. Our population may have unique age-related methylation changes that are not captured in the established methylation-based age prediction model we used, which was developed to be non-tissue-specific.

scholarly journals Relation of Helicobacter pylori to the human gastric mucosa in chronic gastritis of the antrum.

Gut ◽  
1990 ◽  
Vol 31 (11) ◽  
pp. 1230-1236 ◽  
Author(s):  
L L Thomsen ◽  
J B Gavin ◽  
C Tasman-Jones
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Chronic Gastritis ◽  
Human Gastric Mucosa

Helicobacter pylori eradication attenuates oxidative stress in human gastric mucosa

2001 ◽  
Vol 96 (6) ◽  
pp. 1758-1766 ◽  
Author(s):  
Brigitte Pignatelli ◽  
Brigitte Bancel ◽  
Martin Plummer ◽  
Shinya Toyokuni ◽  
Louis-Marc Patricot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Human Gastric Mucosa ◽  
Helicobacter Pylori Eradication

scholarly journals Gastrokine 1 Expression in the Human Gastric Mucosa Is Closely Associated with the Degree of Gastritis and DNA Methylation

2013 ◽  
Vol 13 (4) ◽  
pp. 232 ◽  
Author(s):  
Won Suk Choi ◽  
Ho Suk Seo ◽  
Kyo Young Song ◽  
Jung Hwan Yoon ◽  
Olga Kim ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gastric Mucosa ◽  
Human Gastric Mucosa ◽  
Gastrokine 1

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 Creating and validating a DNA methylation-based proxy for Interleukin-6

2020 ◽  
Author(s):  
Anna J Stevenson ◽  
Danni A Gadd ◽  
Robert Francis Hillary ◽  
Daniel L. McCartney ◽  
Archie Campbell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cognitive Functioning ◽  
Cognitive Ability ◽  
Chronic Inflammation ◽  
Interleukin 6 ◽  
Epigenetic Mechanism ◽  
Inverse Association ◽  
Age Related ◽  
Independent Test ◽  
Methylation Score

Chronic inflammation is a pervasive feature of ageing and may be linked to age-related cognitive decline. However, population studies evaluating its relationship with cognitive functioning have produced heterogeneous results. A potential reason for this is the variability of inflammatory mediators which could lead to misclassifications of individuals' persisting levels of inflammation. The epigenetic mechanism DNA methylation has shown utility in indexing environmental exposures and could potentially be leveraged to provide proxy signatures of chronic inflammation. We conducted an elastic net regression of interleukin-6 (IL-6) in a cohort of 895 older adults (mean age: 69 years) to develop a DNA methylation-based predictor. The predictor was tested in an independent cohort (n=7,028 [417 with measured IL-6], mean age: 51 years).We examined the association between the DNA methylation IL-6 score and serum IL-6, its association with age and established correlates of circulating IL-6, and with cognitive ability. A weighted score from 12 DNA methylation sites optimally predicted IL-6 (independent test set R2=5.1%). In the independent test cohort, both measured IL-6, and the DNA methylation proxy, increased as a function of age (serum IL-6: n=417, β=0.02, SE=0.004 p=1.3x10-7; DNAm IL-6 score: n=7,028, β=0.02, SE=0.0009, p<2x10-16). Serum IL-6 was not found to associate with cognitive ability (n=417, β=-0.06, SE=0.05, p=0.19); however, an inverse association was identified between the DNA methylation score and cognitive functioning (n=7,028, β=-0.14, SE=0.02, pFDR=1.5x10-14). These results suggest DNA methylation-based predictors can be used as proxies for inflammatory markers, potentially allowing for reliable insights into the relationship between chronic inflammation and pertinent health outcomes.

Helicobacter pylori (H. pylori) infection increases IL-8 and IL-6 production from human gastric mucosa

1995 ◽  
Vol 108 (4) ◽  
pp. A769
Author(s):  
T. Ando ◽  
K. Kusugami ◽  
M. Sakakibara ◽  
T. Shimizu ◽  
M. Shinoda ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Human Gastric Mucosa ◽  
H Pylori
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