scholarly journals Nutritional Factors Modulating Alu Methylation in an Italian Sample from The Mark-Age Study Including Offspring of Healthy Nonagenarians

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2986
Author(s):  
Robertina Giacconi ◽  
Marco Malavolta ◽  
Alexander Bürkle ◽  
María Moreno-Villanueva ◽  
Claudio Franceschi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Preliminary Investigation ◽  
Methylation Status ◽  
Dietary Factors ◽  
Elderly Subjects ◽  
Nutritional Factors ◽  
Age Related ◽  
Potential Marker ◽  
Plasma Copper ◽  
Risk Of Disease

Alu hypomethylation promotes genomic instability and is associated with aging and age-related diseases. Dietary factors affect global DNA methylation, leading to changes in genomic stability and gene expression with an impact on longevity and the risk of disease. This preliminary study aims to investigate the relationship between nutritional factors, such as circulating trace elements, lipids and antioxidants, and Alu methylation in elderly subjects and offspring of healthy nonagenarians. Alu DNA methylation was analyzed in sixty RASIG (randomly recruited age-stratified individuals from the general population) and thirty-two GO (GeHA offspring) enrolled in Italy in the framework of the MARK-AGE project. Factor analysis revealed a different clustering between Alu CpG1 and the other CpG sites. RASIG over 65 years showed lower Alu CpG1 methylation than those of GO subjects in the same age class. Moreover, Alu CpG1 methylation was associated with fruit and whole-grain bread consumption, LDL2-Cholesterol and plasma copper. The preserved Alu methylation status in GO, suggests Alu epigenetic changes as a potential marker of aging. Our preliminary investigation shows that Alu methylation may be affected by food rich in fibers and antioxidants, or circulating LDL subfractions and plasma copper.

scholarly journals DNA methylation differs extensively between strains of the same geographical origin and changes with age in Daphnia magna

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jack Hearn ◽  
Fiona Plenderleith ◽  
Tom J. Little
Keyword(s):  
Dna Methylation ◽  
Caloric Restriction ◽  
Daphnia Magna ◽  
Single Gene ◽  
Methylation Status ◽  
Strain Differences ◽  
Life History Trait ◽  
Food Level ◽  
Epigenetic Clock ◽  
Age Related

Abstract Background Patterns of methylation influence lifespan, but methylation and lifespan may also depend on diet, or differ between genotypes. Prior to this study, interactions between diet and genotype have not been explored together to determine their influence on methylation. The invertebrate Daphnia magna is an excellent choice for testing the epigenetic response to the environment: parthenogenetic offspring are identical to their siblings (making for powerful genetic comparisons), they are relatively short lived and have well-characterised inter-strain life-history trait differences. We performed a survival analysis in response to caloric restriction and then undertook a 47-replicate experiment testing the DNA methylation response to ageing and caloric restriction of two strains of D. magna. Results Methylated cytosines (CpGs) were most prevalent in exons two to five of gene bodies. One strain exhibited a significantly increased lifespan in response to caloric restriction, but there was no effect of food-level CpG methylation status. Inter-strain differences dominated the methylation experiment with over 15,000 differently methylated CpGs. One gene, Me31b, was hypermethylated extensively in one strain and is a key regulator of embryonic expression. Sixty-one CpGs were differentially methylated between young and old individuals, including multiple CpGs within the histone H3 gene, which were hypermethylated in old individuals. Across all age-related CpGs, we identified a set that are highly correlated with chronological age. Conclusions Methylated cytosines are concentrated in early exons of gene sequences indicative of a directed, non-random, process despite the low overall DNA methylation percentage in this species. We identify no effect of caloric restriction on DNA methylation, contrary to our previous results, and established impacts of caloric restriction on phenotype and gene expression. We propose our approach here is more robust in invertebrates given genome-wide CpG distributions. For both strain and ageing, a single gene emerges as differentially methylated that for each factor could have widespread phenotypic effects. Our data showed the potential for an epigenetic clock at a subset of age positions, which is exciting but requires confirmation.

scholarly journals Nutritional factors and gender influence age‐related DNA methylation in the human rectal mucosa

Aging Cell ◽  
2012 ◽  
Vol 12 (1) ◽  
pp. 148-155 ◽  
Author(s):  
Henri S. Tapp ◽  
Daniel M. Commane ◽  
D. Michael Bradburn ◽  
Ramesh Arasaradnam ◽  
John C. Mathers ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rectal Mucosa ◽  
Nutritional Factors ◽  
Gender Influence ◽  
Age Related ◽  
And Gender

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

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.

scholarly journals DNA Methylation in Neurodegenerative and Cerebrovascular Disorders

2020 ◽  
Vol 21 (6) ◽  
pp. 2220 ◽  
Author(s):  
Olaia Martínez-Iglesias ◽  
Iván Carrera ◽  
Juan Carlos Carril ◽  
Lucía Fernández-Novoa ◽  
Natalia Cacabelos ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Expression Regulation ◽  
Methylation Status ◽  
Cerebrovascular Disorders ◽  
Cerebrovascular Diseases ◽  
Epigenetic Mechanism ◽  
Mrna Levels ◽  
Serum Samples ◽  
Global Methylation ◽  
Age Related

DNA methylation is an epigenetic mechanism by which methyl groups are added to DNA, playing a crucial role in gene expression regulation. The aim of the present study is to compare methylation status of healthy subjects with that of patients with Alzheimer’s, Parkinson’s or Cerebrovascular diseases. We also analyze methylation status of a transgenic Alzheimer’s disease mouse model (3xTg-AD). Our results show that both global methylation (n = 141) and hydroxymethylation (n = 131) levels are reduced in DNA samples from buffy coats of patients with neurodegenerative disorders and age-related cerebrovascular disease. The importance of methylation and hydroxymethylation reduction is stressed by the finding that DNMT3a mRNA levels are also downregulated in buffy coats of patients with Dementia (n = 25). Global methylation is also reduced in brain, liver and serum samples of 3xTg-AD vs. wild type mice, such as DNMT3a mRNA levels that are also decreased in the brain of 3xTg-AD (n = 10). These results suggest that the use of global methylation and hydroxymethylation levels, together with the study of DNMT3a expression, could be useful as a new diagnostic biomarker for these prevalent disorders.

scholarly journals Alcohol consumption is associated with widespread changes in blood DNA methylation: analysis of cross-sectional and longitudinal data

2018 ◽  
Author(s):  
Pierre-Antoine Dugué ◽  
Rory Wilson ◽  
Benjamin Lehne ◽  
Harindra Jayasekara ◽  
Xiaochuan Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Consumption ◽  
Large Scale ◽  
Alcohol Intake ◽  
Methylation Status ◽  
Repeated Measurements ◽  
Cross Sectional ◽  
Blood Samples ◽  
Melbourne Collaborative Cohort Study ◽  
Risk Of Disease

ABSTRACTBackground:DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart.Methods:Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined using baseline peripheral blood samples from 5,606 adult Melbourne Collaborative Cohort Study (MCCS) participants. For a subset of 1,088 of them, these measures were repeated using blood samples collected at follow-up, a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. Independent data from the LOLIPOP (N=4,042) and KORA (N=1,662) cohorts were used to replicate associations discovered in the MCCS.Results:Cross-sectional analyses identified 1,414 CpGs associated with alcohol intake at P<10-7, 1,243 of which had not been reported previously. Of these 1,243 novel associations, 1,078 were replicated (P<0.05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated (P<0.05) 403 of 518 associations that had been reported previously. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1,414 CpGs, 530 were differentially methylated (P<0.05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1,414 cross-sectional associations.Conclusion:Our study indicates that, for middle-aged and older adults, alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with changes in alcohol consumption.

scholarly journals Regular, Intense Exercise Training as a Healthy Aging Lifestyle Strategy: Preventing DNA Damage, Telomere Shortening and Adverse DNA Methylation Changes Over a Lifetime

2021 ◽  
Vol 12 ◽  
Author(s):  
Maha Sellami ◽  
Nicola Bragazzi ◽  
Mohammad Shoaib Prince ◽  
Joshua Denham ◽  
Mohamed Elrayess
Keyword(s):  
Dna Methylation ◽  
Dna Damage ◽  
Exercise Training ◽  
Epigenetic Modification ◽  
Methylation Status ◽  
The Body ◽  
Training Load ◽  
Activity Level ◽  
Biological Aging ◽  
Age Related

Exercise training is one of the few therapeutic interventions that improves health span by delaying the onset of age-related diseases and preventing early death. The length of telomeres, the 5′-TTAGGGn-3′ tandem repeats at the ends of mammalian chromosomes, is one of the main indicators of biological age. Telomeres undergo shortening with each cellular division. This subsequently leads to alterations in the expression of several genes that encode vital proteins with critical functions in many tissues throughout the body, and ultimately impacts cardiovascular, immune and muscle physiology. The sub-telomeric DNA is comprised of heavily methylated, heterochromatin. Methylation and histone acetylation are two of the most well-studied examples of the epigenetic modifications that occur on histone proteins. DNA methylation is the type of epigenetic modification that alters gene expression without modifying gene sequence. Although diet, genetic predisposition and a healthy lifestyle seem to alter DNA methylation and telomere length (TL), recent evidence suggests that training status or physical fitness are some of the major factors that control DNA structural modifications. In fact, TL is positively associated with cardiorespiratory fitness, physical activity level (sedentary, active, moderately trained, or elite) and training intensity, but is shorter in over-trained athletes. Similarly, somatic cells are vulnerable to exercise-induced epigenetic modification, including DNA methylation. Exercise-training load, however, depends on intensity and volume (duration and frequency). Training load-dependent responses in genomic profiles could underpin the discordant physiological and physical responses to exercise. In the current review, we will discuss the role of various forms of exercise training in the regulation of DNA damage, TL and DNA methylation status in humans, to provide an update on the influence exercise training has on biological aging.

scholarly journals DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Pamela R. Matías-García ◽  
Cavin K. Ward-Caviness ◽  
Laura M. Raffield ◽  
Xu Gao ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
African American ◽  
Kidney Disease ◽  
Meta Analysis ◽  
Methylation Status ◽  
Serum Urate ◽  
Biological Aging ◽  
Epigenetic Biomarkers ◽  
Age Related ◽  
New Findings

Abstract Background The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E−03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang’s 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β =  − 0.12, 95% CI = [− 0.16, − 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E−08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E−06). The “first-generation” clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.

scholarly journals Global DNA methylation in rats´ liver is not affected by hypercholesterolemic diet

2020 ◽  
pp. 347-352
Author(s):  
L. Jurcikova-Novotna ◽  
L. Mrazova ◽  
K. Micova ◽  
D. Friedecky ◽  
J.A. Hubacek ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Plasma Cholesterol ◽  
Methylation Status ◽  
Dietary Factors ◽  
Rat Strains ◽  
Total Liver ◽  
Cholesterol Levels ◽  
Hypercholesterolemic Diet ◽  
Wistar Kyoto ◽  
Atherosclerosis Risk Factors

Increased plasma cholesterol levels are listed between the major atherosclerosis risk factors. The final plasma cholesterol levels result from the interplay between the genetic and environmental (diet, physical activity) factors. Little is known, how dietary factors influence epigenetics. We have analyzed, if an over-generation feeding of rat with cholesterol influences total liver-DNA methylation, and if total liver-DNA methylation differ between the different rat strains (Prague hereditary hypercholesterolemic rats, Prague hereditary hypertriglyceridemic rats and Wistar Kyoto rats). The animals were feed with high fat (additional 5 % over normal capacity) high cholesterol (2 %) diet for 14 days. DNA methylation in the liver tissue in different generations was analyzed using the liquid chromatography coupled with tandem mass spectrometry. We have not observed any significant changes in total liver-DNA methylation over the 9 generations of animals feed by fat/cholesterol enriched diet. Additionally, there were no differences in DNA methylation between different rat strains. In animal model, the dietary changes (hypercholesterolemic diet) not significantly influence the total DNA methylation status within the liver.

scholarly journals Age-related Changes in DNA Methylation Status of hTERT Gene Promoter of Oral Epithelial Cells

2014 ◽  
Vol 58 (1) ◽  
pp. 82-89 ◽  
Author(s):  
Stephane Flaviane de Oliveira Bezerra ◽  
Ludimila de Araújo Costa ◽  
Priscylla Alves Nascimento de Freitas ◽  
Naila Francis Paulo de Oliveira
Keyword(s):  
Dna Methylation ◽  
Epithelial Cells ◽  
Methylation Status ◽  
Gene Promoter ◽  
Htert Gene ◽  
Oral Epithelial Cells ◽  
Age Related ◽  
Oral Epithelial ◽  
Age Related Changes

scholarly journals DNA methylation outlier burden, health and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936

2019 ◽  
Author(s):  
Anne Seeboth ◽  
Daniel L. McCartney ◽  
Yunzhang Wang ◽  
Robert F. Hillary ◽  
Anna J. Stevenson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Meta Analysis ◽  
Family Health ◽  
Small Samples ◽  
Health Study ◽  
Birth Cohorts ◽  
Cross Sectional ◽  
Age Related ◽  
Potential Marker ◽  
Generation Scotland

AbstractDNA methylation outlier burden has been suggested as a potential marker of biological age. An outlier is typically defined as DNA methylation levels at any one CpG site that are three times beyond the inter-quartile range from the 25th or 75th percentiles compared to the rest of the population. DNA methylation outlier burden (the number of such outlier sites per individual) increases exponentially with age. However, these findings have been observed in small samples. Here, we showed an association between age and log10-transformed DNA methylation outlier burden in a large cross-sectional cohort, the Generation Scotland Family Health Study (N=7,010, β=0.0091, p<2×10−16), and in two longitudinal cohort studies, the Lothian Birth Cohorts of 1921 (N=430, β=0.033, p=7.9×10−4) and 1936 (N=898, β=7.9×10−3, p=0.074). Significant confounders of both cross-sectional and longitudinal associations between outlier burden and age included white blood cell proportions, BMI, smoking, and batch effects. In Generation Scotland, the increase in epigenetic outlier burden with age was not purely an artefact of an increase in DNA methylation level variability with age (epigenetic drift). Log10-transformed DNA methylation outlier burden in Generation Scotland was not related to self-reported, or family history of, age-related diseases and it was not heritable (SNP-based heritability of 4.4%, p=0.18). Finally, DNA methylation outlier burden was not significantly related to survival in either of the Lothian Birth Cohorts individually but it was in a meta-analysis (HRmeta=1.12; 95%CImeta=[1.02; 1.21]; pmeta=0.021). These findings suggest that, while it does not associate with ageing-related health outcomes, DNA methylation outlier burden does track chronological ageing and may also relate to survival. DNA methylation outlier burden may thus be useful as a marker of biological ageing.

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