Aberrant Methylation of Aging-Related Genes in Asthma

Background: Asthma is a complex pulmonary inflammatory disease which is common among older adults. Aging-related alterations have also been found in structural cells and immune cells of asthma patients. Nonetheless, the underlying mechanism by which differenced aging-related gene contributes to asthma pathology remains unclear. Of note, DNA methylation (DNAm) has been proven to play a critical mechanism for age-related gene expression changes. However, the methylation changes of aging-related genes in asthma patients are still obscure.Methods: First, changes in DNAm and gene expression were detected with multiple targeted bisulfite enrichment sequencing (MethTarget) and qPCR in peripheral blood of 51 healthy controls (HCs) and 55 asthmatic patients. Second, the correlation between the DNAm levels of specific altered CpG sites and the pulmonary function indicators of asthma patients was evaluated. Last, the receiver operator characteristic (ROC) curve and principal component analysis (PCA) were used to identify the feasibility of the candidate CpG sites as biomarkers for asthma.Results: Compared with HCs, there was a differential mRNA expression for nine aging-related genes in peripheral blood of asthma patients. Besides, the methylation levels of the nine aging-related genes were also altered in asthma patients, and a total of 68 CpG sites were associated with the severity of asthma. Notably, 9 of the 68 CpG sites were significantly associated with pulmonary function parameters. Moreover, ROC curve and PCA analysis showed that the candidate differential methylation sites (DMSs) can be used as potential biomarkers for asthma.Conclusions: In summary, this study confirmed the differentially expressed mRNA and aberrant DNAm level of aging-related genes in asthma patients. DMSs are associated with the clinical evaluation indicators of asthma, which indicate the involvement of aging-related genes in the pathogenesis of asthma and provide some new possible biomarkers for asthma.

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Variable expressed methylation sites of aging-related genes in asthma

10.21203/rs.3.rs-84789/v1 ◽

2020 ◽

Author(s):

Yu Yang ◽

Lin Yuan ◽

Ming Yang ◽

Xizi Du ◽

Ling Qin ◽

...

Keyword(s):

Pulmonary Function ◽

Mrna Expression ◽

Roc Curve ◽

Peripheral Blood ◽

Principal Component ◽

Mrna Levels ◽

Related Gene ◽

Cpg Sites ◽

Asthma Patients ◽

Dnam Level

Abstract Background: Asthma is a complex pulmonary inflammatory disease which is common in the elderly. Aging-related alterations have also been found in the structural cells and immune cells of asthma patients although the pathological mechanism of the differential aging-related gene in the development of asthma is still obscure. Of note, DNA methylation (DNAm) have been proven to play an important role in the regulation of aging-related genes. However, the methylation levels of aging-related genes in asthma patients are largely unclear.Methods: First, the mRNA levels and DNAm level of the previous screened 9 aging-related genes in peripheral blood of 51 healthy controls (HCs) and 55 asthmatic patients were detected by multiple targeted bisulfite enrichment sequencing (MethTarget) and qPCR. Secondly, the correlation between the DNAm level of specific altered CpG sites and the pulmonary function indicators of asthma patients was evaluated. Lastly, the Receiver Operator Characteristic (ROC) curve and Principal Component Analysis (PCA) were used to identify the feasibility of the candidate CpG sites as asthma markers.Results: The mRNA expression of the 9 aging-related gene in peripheral blood of asthma patients was significantly different from those of HCs. Besides, the methylation level of the 9 aging-related genes also altered in asthma patients, and a total of 68 CpG sites were related to the severity of asthma. Notably, 10 of the 68 CpG sites had a significant relationship with pulmonary function parameters. Moreover, ROC curve and PCA analysis showed that the candidate differential methylation sites (DMSs) can be used as potential biomarkers for asthma.Conclusions: In summary, this study confirmed the changes in the mRNA expression and DNAm level of aging-related genes in asthma patients. The differential DMSs are associated with the clinical evaluation indicators of asthma, which may indicate the involvement of aging-related genes in the pathogenesis of asthma and provide some new possible biomarker of asthma.

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Variable Expressed Methylation Sites of Aging-related Genes in Asthma

10.21203/rs.3.rs-60066/v1 ◽

2020 ◽

Author(s):

Yu Yang ◽

Lin Yuan ◽

Ming Yang ◽

Xizi Du ◽

Ling Qin ◽

...

Keyword(s):

Pulmonary Function ◽

Mrna Expression ◽

Roc Curve ◽

Peripheral Blood ◽

Principal Component ◽

Mrna Levels ◽

Related Gene ◽

Cpg Sites ◽

Asthma Patients ◽

Dnam Level

Abstract Background: Asthma is a complex pulmonary inflammatory disease which is common in the elderly. Aging-related alterations have also been found in the structural cells and immune cells of asthma patients although the pathological mechanism of the differential aging-related gene in the development of asthma is still obscure. Of note, DNA methylation (DNAm) have been proven to play an important role in the regulation of aging-related genes. However, the methylation levels of aging-related genes in asthma patients are largely unclear.Methods: First, the mRNA levels and DNAm level of the previous screened 9 aging-related genes in peripheral blood of 51 healthy controls (HCs) and 55 asthmatic patients were detected by multiple targeted bisulfite enrichment sequencing (MethTarget) and qPCR. Secondly, the correlation between the DNAm level of specific altered CpG sites and the pulmonary function indicators of asthma patients was evaluated. Lastly, the Receiver Operator Characteristic (ROC) curve and Principal Component Analysis (PCA) were used to identify the feasibility of the candidate CpG sites as asthma markers.Results: The mRNA expression of the 9 aging-related gene in peripheral blood of asthma patients was significantly different from those of HCs. Besides, the methylation level of the 9 aging-related genes also altered in asthma patients, and a total of 68 CpG sites were related to the severity of asthma. Notably, 10 of the 68 CpG sites had a significant relationship with pulmonary function parameters. Moreover, ROC curve and PCA analysis showed that the candidate differential methylation sites (DMSs) can be used as potential biomarkers for asthma.Conclusions:In summary, this study confirmed the changes in the mRNA expression and DNAm level of aging-related genes in asthma patients. The differential DMSs are associated with the clinical evaluation indicators of asthma, which may indicate the involvement of aging-related genes in the pathogenesis of asthma and provide some new possible biomarker of asthma.

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Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

Scientific Reports ◽

10.1038/srep15145 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 98

Author(s):

Jialiang Yang ◽

◽

Tao Huang ◽

Francesca Petralia ◽

Quan Long ◽

...

Keyword(s):

Gene Expression ◽

Complex Disease ◽

Principal Component ◽

Tissue Expression ◽

Whole Body ◽

Disease Genes ◽

Related Gene ◽

Tissue Specific ◽

Age Related ◽

Holistic Understanding

Abstract Aging is one of the most important biological processes and is a known risk factor for many age-related diseases in human. Studying age-related transcriptomic changes in tissues across the whole body can provide valuable information for a holistic understanding of this fundamental process. In this work, we catalogue age-related gene expression changes in nine tissues from nearly two hundred individuals collected by the Genotype-Tissue Expression (GTEx) project. In general, we find the aging gene expression signatures are very tissue specific. However, enrichment for some well-known aging components such as mitochondria biology is observed in many tissues. Different levels of cross-tissue synchronization of age-related gene expression changes are observed and some essential tissues (e.g., heart and lung) show much stronger “co-aging” than other tissues based on a principal component analysis. The aging gene signatures and complex disease genes show a complex overlapping pattern and only in some cases, we see that they are significantly overlapped in the tissues affected by the corresponding diseases. In summary, our analyses provide novel insights to the co-regulation of age-related gene expression in multiple tissues; it also presents a tissue-specific view of the link between aging and age-related diseases.

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Do age-related changes in DNA methylation play a role in the development of age-related diseases?

Biochemical Society Transactions ◽

10.1042/bst20120358 ◽

2013 ◽

Vol 41 (3) ◽

pp. 803-807 ◽

Cited By ~ 26

Author(s):

Sanne D. van Otterdijk ◽

John C. Mathers ◽

Gordon Strathdee

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Cpg Islands ◽

Large Body ◽

Epigenetic Mechanism ◽

Aberrant Methylation ◽

Gene Promoters ◽

Cpg Sites ◽

Pathological Conditions ◽

Age Related

DNA methylation is an important epigenetic mechanism in mammalian cells. It occurs almost exclusively at CpG sites and has a key role in a number of biological processes. It plays an important part in regulating chromatin structure and has been best studied for its role in controlling gene expression. In particular, hypermethylation of gene promoters which have high levels of CpG sites, known as CpG islands, leads to gene inactivation. In healthy cells, however, it appears that only a small number of genes are controlled through promoter hypermethylation, such as genes on the inactivated X-chromosome or at imprinted loci, and most promoter-associated CpG islands remain methylation-free regardless of gene expression status. However, a large body of evidence has now shown that this protection from methylation not only breaks down in a number of pathological conditions (e.g. cancer), but also already occurs during the normal process of aging. The present review focuses on the methylation changes that occur during healthy aging and during disease development, and the potential links between them. We focus especially on the extent to which the acquisition of aberrant methylation changes during aging could underlie the development of a number of important age-related pathological conditions.

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Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

Immunity & Ageing ◽

10.1186/s12979-021-00223-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Katherine R. Dobbs ◽

Paula Embury ◽

Emmily Koech ◽

Sidney Ogolla ◽

Stephen Munga ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Young Adults ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Innate Immune ◽

Inflammatory Gene Expression ◽

Cpg Sites ◽

Age Related ◽

Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

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Abstract 3259: Leukocyte Subset Specific Gene Expression In Acute Stroke Patients

Stroke ◽

10.1161/str.43.suppl_1.a3259 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Mateusz G Adamski ◽

Yan Li ◽

Hua Yu ◽

Erin Wagner ◽

Sareen Amarjeet ◽

...

Keyword(s):

Gene Expression ◽

Acute Stroke ◽

Whole Blood ◽

Peripheral Blood ◽

Fold Increase ◽

Specific Gene ◽

Related Gene ◽

Stroke Patients ◽

Leukocyte Subset ◽

Control Subjects

Background: Alterations in gene expression in the peripheral blood of patients with acute stroke have been demonstrated using microarray technology. Whole blood and peripheral blood mononuclear cells (PBMCs) were used in prior studies in which panels of genes diagnostic for stroke were developed. We aimed to determine the cellular sources of alterations in gene expression by studying individual leukocyte subsets. Methods: The expression of four genes previously found to be upregulated in ischemic and hemorrhagic stroke (IL1R2, S100A9, ETS2 and F5) was measured in four leukocyte subsets: CD14+ monocytes, CD4+ T cell lymphocytes, CD20+ B cell lymphocytes and PBMCs. These four genes had been reported in at least two of the previously published stroke-related gene panels. Peripheral blood was obtained from six acute stroke patients (all <48 hours from symptom onset) and 6 age, race and sex matched control subjects. Leukocytes were separated from whole blood using density gradient centrifugation and column magnetic bead cell sorting. The purity of separated leukocyte subsets exceeded 90% and was verified with flow cytometry. Messenger RNA was isolated from each leukocyte subset and analyzed by two step RT PCR and qPCR. The expression of the four stroke-related genes was compared to the expression of a housekeeping gene (GAPDH). The relative expression of individual genes and of the 4 gene panel within cellular subsets was compared between stroke patients and control subjects. Results: Individually, IL1R2 and S100A9 were significantly over-expressed in stroke patients with a 10 fold increase for IL1R2 in PBMCs (p<0.05) and a 3 fold increase for S100A9 in the CD4+ T and CD20+ B lymphocyte subsets (p<0.05). When analyzed as a panel of four genes the expression of IL1R2, S100A9, ETS2 and F5 was significantly higher in both the CD4+ T lymphocytes (p<0.05) and CD20+ B lymphocytes (p<0.05) of stroke patients but not in the monocytes or the PBMCs. Conclusion: These results show the potential diagnostic value of selected genes from panels previously found in microarray studies in stroke patients. They also emphasize the value of panel analysis over that of single gene expression and the potential cellular specificity of alterations in gene expression. Analysis of whole blood and PBMCs alone may not reflect important dynamic changes in stroke-related gene expression.

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The Effect of Sulforaphane on Glyoxalase I Expression and Activity in Peripheral Blood Mononuclear Cells

Nutrients ◽

10.3390/nu10111773 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1773 ◽

Cited By ~ 6

Author(s):

Michela Alfarano ◽

Donato Pastore ◽

Vincenzo Fogliano ◽

Casper Schalkwijk ◽

Teresa Oliviero

Keyword(s):

Gene Expression ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Limit Of Detection ◽

Peripheral Blood Mononuclear ◽

Potential Health ◽

Age Related ◽

Blood Mononuclear Cells ◽

Expression Activity

Studies demonstrate that the potential health-beneficial effect of sulforaphane (SR), a compound formed in broccoli, is the result of a number of mechanisms including upregulation of phase two detoxification enzymes. Recent studies suggest that SR increases expression/activity of glyoxalase 1 (Glo1), an enzyme involved in the degradation of methylglyoxal, is major precursor of advanced glycation end products. Those compounds are associated with diabetes complications and other age-related diseases. In this study, the effect of SR on the expression/activity of Glo1 in peripheral blood mononuclear cells (PBMCs) from 8 healthy volunteers was investigated. PBMCs were isolated and incubated with SR (2.5 μM-concentration achievable by consuming a broccoli portion) for 24 h and 48 h. Glo1 activity/expression, reduced glutathione (GSH), and glutathione-S-transferase gene expression were measured. Glo1 activity was not affected while after 48 h a slight but significant increase of its gene expression (1.03-fold) was observed. GSTP1 expression slightly increased after 24 h incubation (1.08-fold) while the expressions of isoform GSTT2 and GSTM2 were below the limit of detection. GSH sharply decreased, suggesting the formation of GSH-SR adducts that may have an impact SR availability. Those results suggest that a regular exposure to SR by broccoli consumption or SR supplements may enhance Glo1.

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Age-related gene expression and DNA methylation changes in rhesus macaque

Genomics ◽

10.1016/j.ygeno.2020.09.021 ◽

2020 ◽

Vol 112 (6) ◽

pp. 5147-5156

Author(s):

Min Zhou ◽

Liang Zhang ◽

Qiao Yang ◽

Chaochao Yan ◽

Peng Jiang ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Rhesus Macaque ◽

Related Gene ◽

Age Related

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Changes in DNA Methylation and Gene Expression of Insulin and Obesity-Related Gene PIK3R1 after Roux-en-Y Gastric Bypass

International Journal of Molecular Sciences ◽

10.3390/ijms21124476 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4476

Author(s):

Marcela A S Pinhel ◽

Natália Y Noronha ◽

Carolina F Nicoletti ◽

Vanessa AB Pereira ◽

Bruno AP de Oliveira ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Weight Loss ◽

Gastric Bypass ◽

Related Gene ◽

Cpg Sites ◽

Genome Wide ◽

Genetically Determined ◽

Methylation Patterns ◽

Weight Loss Interventions

Weight regulation and the magnitude of weight loss after a Roux-en-Y gastric bypass (RYGB) can be genetically determined. DNA methylation patterns and the expression of some genes can be altered after weight loss interventions, including RYGB. The present study aimed to evaluate how the gene expression and DNA methylation of PIK3R1, an obesity and insulin-related gene, change after RYGB. Blood samples were obtained from 13 women (35.9 ± 9.2 years) with severe obesity before and six months after surgical procedure. Whole blood transcriptome and epigenomic patterns were assessed by microarray-based, genome-wide technologies. A total of 1966 differentially expressed genes were identified in the pre- and postoperative periods of RYGB. From these, we observed that genes involved in obesity and insulin pathways were upregulated after surgery. Then, the PIK3R1 gene was selected for further RT-qPCR analysis and cytosine-guanine nucleotide (CpG) sites methylation evaluation. We observed that the PI3KR1 gene was upregulated, and six DNA methylation CpG sites were differently methylated after bariatric surgery. In conclusion, we found that RYGB upregulates genes involved in obesity and insulin pathways.

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