DbDMAD: a Database of DNA Methylation in Human Age-related Disease

Wei Zhang; Chang Linghu; Juhua Zhang

doi:10.5815/ijem.2012.05.02

A Genome-Wide Scan Reveals Important Roles of DNA Methylation in Human Longevity by Regulating Age-Related Disease Genes

PLoS ONE ◽

10.1371/journal.pone.0120388 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0120388 ◽

Cited By ~ 19

Author(s):

Fu-Hui Xiao ◽

Yong-Han He ◽

Qi-Gang Li ◽

Huan Wu ◽

Long-Hai Luo ◽

...

Keyword(s):

Dna Methylation ◽

Human Longevity ◽

Disease Genes ◽

Related Disease ◽

Age Related ◽

Genome Wide ◽

A Genome ◽

Genome Wide Scan

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Electrochemically detecting DNA methylation in the EN1 gene promoter: implications for understanding ageing and disease

Bioscience Reports ◽

10.1042/bsr20202571 ◽

2020 ◽

Vol 40 (11) ◽

Author(s):

Amy E. Morgan ◽

Katie D. Acutt ◽

Mark T. Mc Auley

Keyword(s):

Dna Methylation ◽

Methylation Status ◽

Gene Promoter ◽

Gene Promoters ◽

Developmental Genes ◽

Transfer Resistance ◽

Related Disease ◽

Age Related ◽

Electrochemical Approach ◽

The Future

Abstract There is a growing need for biomarkers which predict age-onset pathology. Although this is challenging, the methylome offers significant potential. Cancer is associated with the hypermethylation of many gene promoters, among which are developmental genes. Evolutionary theory suggests developmental genes arbitrate early-late life trade-offs, causing epimutations that increase disease vulnerability. Such genes could predict age-related disease. The aim of this work was to optimise an electrochemical procedure for the future investigation of a broad range of ageing-related pathologies. An electrochemical approach, which adopted three analytical techniques, was used to investigate DNA methylation in the engrailed-1 (EN1) gene promoter. Using synthetic single-stranded DNA, one technique was able to detect DNA at concentrations as low as 10 nM, with methylation status distinguishable at concentrations >25 nM. A negative correlation could be observed between % methylation of a heterogeneous solution and the key electrochemical parameter, charge transfer resistance (Rct; r = −0.982, P<0.01). The technique was applied to the breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), where a similar correlation was observed (r = −0.965, P<0.01). These results suggest electrochemistry can effectively measure DNA methylation at low concentrations of DNA. This has implications for the future detection of age-related disease.

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Nutritional influences on epigenetics and age-related disease

Proceedings of The Nutrition Society ◽

10.1017/s0029665111003302 ◽

2011 ◽

Vol 71 (1) ◽

pp. 75-83 ◽

Cited By ~ 111

Author(s):

Lara K. Park ◽

Simonetta Friso ◽

Sang-Woon Choi

Keyword(s):

Dna Methylation ◽

Histone Modifications ◽

Healthy Aging ◽

Vitamin B ◽

Related Disease ◽

Age Related ◽

Nutritional Influences ◽

One Carbon Metabolism ◽

Epigenetic Patterns ◽

Future Work

Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modulates gene expression without changes in the underlying bp sequence, ultimately determining phenotype from genotype. DNA methylation and post-translational histone modifications are classical levels of epigenetic regulation. Epigenetic phenomena are critical from embryonic development through the aging process, with aberrations in epigenetic patterns emerging as aetiological mechanisms in many age-related diseases such as cancer, CVD and neurodegenerative disorders. Nutrients can act as the source of epigenetic modifications and can regulate the placement of these modifications. Nutrients involved in one-carbon metabolism, namely folate, vitamin B12, vitamin B6, riboflavin, methionine, choline and betaine, are involved in DNA methylation by regulating levels of the universal methyl donor S-adenosylmethionine and methyltransferase inhibitor S-adenosylhomocysteine. Other nutrients and bioactive food components such as retinoic acid, resveratrol, curcumin, sulforaphane and tea polyphenols can modulate epigenetic patterns by altering the levels of S-adenosylmethionine and S-adenosylhomocysteine or directing the enzymes that catalyse DNA methylation and histone modifications. Aging and age-related diseases are associated with profound changes in epigenetic patterns, though it is not yet known whether these changes are programmatic or stochastic in nature. Future work in this field seeks to characterise the epigenetic pattern of healthy aging to ultimately identify nutritional measures to achieve this pattern.

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Current Understanding of DNA Methylation and Age-related Disease

10.21926/obm.genet.1802016 ◽

2018 ◽

Vol 2 (2) ◽

pp. 1-1 ◽

Cited By ~ 2

Author(s):

Eunise M. Aquino ◽

◽

Miles C. Benton ◽

Larisa M. Haupt ◽

Heidi G. Sutherland ◽

...

Keyword(s):

Dna Methylation ◽

Current Understanding ◽

Related Disease ◽

Age Related

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EPIGENETICS MARKERS OF AGING AND EXPOSURES

Innovation in Aging ◽

10.1093/geroni/igz038.2695 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S735-S735

Author(s):

Joanne Murabito

Keyword(s):

Dna Methylation ◽

Cohort Studies ◽

Disease Risk ◽

Association Studies ◽

Methylation Data ◽

Expression Data ◽

Cross Sectional ◽

Related Disease ◽

Age Related ◽

Dna Methylation Age

Abstract Widespread changes to the epigenome occur with aging. DNA methylation is one of the most commonly studied epigenetic mechanisms, reflects lifetime exposures that impact aging, and is associated with age-related disease risk. Many longitudinal cohort studies have existing cross-sectional or longitudinal DNA methylation data along with genotype and expression data permitting investigation of relationships between DNA methylation markers, exposures, and disease. The data can be leveraged to conduct large epigenome-wide association studies (EWAS) of aging and age-related disease to identify DNA methylation biomarkers and lead to insights into novel biologic pathways for development of interventions to delay aging. DNA methylation age measures robustly predict chronologic age and associate with both healthspan and lifespan. During the workshop, examples from cohort studies and the CHARGE consortium will be presented.

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The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

Rejuvenation Research ◽

10.1089/rej.2012.1324 ◽

2012 ◽

Vol 15 (5) ◽

pp. 483-494 ◽

Cited By ~ 162

Author(s):

Adiv A. Johnson ◽

Kemal Akman ◽

Stuart R.G. Calimport ◽

Daniel Wuttke ◽

Alexandra Stolzing ◽

...

Keyword(s):

Dna Methylation ◽

Related Disease ◽

Age Related

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A decade of epigenetic change in aging twins: genetic and environmental contributions to longitudinal DNA methylation

10.1101/778555 ◽

2019 ◽

Author(s):

Chandra A. Reynolds ◽

Qihua Tan ◽

Elizabeth Munoz ◽

Juulia Jylhävä ◽

Jacob Hjelmborg ◽

...

Keyword(s):

Dna Methylation ◽

Epigenetic Changes ◽

Time Stability ◽

Related Disease ◽

Age Related ◽

Two Samples ◽

Twin Models ◽

Specific Factors ◽

Blood Leukocyte ◽

Genetic Contributions

Summary/AbstractBackgroundEpigenetic changes may result from the interplay of environmental exposures and genetic influences and contribute to differences in age-related disease, disability and mortality risk. However, the etiologies contributing to stability and change in DNA methylation have rarely been examined longitudinally.MethodsWe considered DNA methylation in whole blood leukocyte DNA across a 10-year span in two samples of same-sex aging twins: (a) Swedish Adoption Twin Study of Aging (SATSA; N = 53 pairs, 53% female; 62.9 and 72.5 years, SD=7.2 years); (b) Longitudinal Study of Aging Danish Twins (LSADT; N = 43 pairs, 72% female, 76.2 and 86.1 years, SD=1.8 years). Joint biometrical analyses were conducted on 358,836 methylation probes in common. Bivariate twin models were fitted, adjusting for age, sex and country.ResultsOverall, results suggest genetic contributions to DNA methylation across 358,836 sites tended to be small and lessen across 10 years (broad heritability M=23.8% and 18.0%) but contributed to stability across time while person-specific factors explained emergent influences across the decade. Aging-specific sites identified from prior EWAS and methylation age clocks were more heritable than background sites. The 5,037 sites that showed the greatest heritable/familial-environmental influences (p<1E-07) were enriched for immune and inflammation pathways while 2,020 low stability sites showed enrichment in stress-related pathways.ConclusionsAcross time, stability in methylation is primarily due to genetic contributions, while novel experiences and exposures contribute to methylation differences. Elevated genetic contributions at age-related methylation sites suggest that adaptions to aging and senescence may be differentially impacted by genetic background.

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