DNA Methylation, Age-Related Immune Defects, and Autoimmunity

2010 ◽  
pp. 327-344
Author(s):  
Jörg J. Goronzy ◽  
Guangjin Li ◽  
Cornelia M. Weyand
Keyword(s):  
Dna Methylation ◽  
Age Related ◽  
Dna Methylation Age ◽  
Immune Defects

scholarly journals Universal DNA Methylation Age Across Mammalian Tissues

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 412-412
Author(s):  
Zhe Fei ◽  
Ken Raj ◽  
Steve Horvath ◽  
Ake Lu
Keyword(s):  
Dna Methylation ◽  
Aging Process ◽  
Mammalian Species ◽  
The Body ◽  
Cellular Damage ◽  
Developmental Processes ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Mammalian Tissues ◽  
Dna Methylation Age

Abstract Aging is often perceived as a degenerative process caused by random accrual of cellular damage over time. In spite of this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, it is difficult to ignore the likelihood that a defined and shared mechanism instead, underlies the aging process. To address this, we generated over 10,000 methylation arrays, each profiling up to 37,000 cytosines in highly-conserved stretches of DNA, from over 59 tissue-types derived from 128 mammalian species. From these, we identified and characterized specific cytosines, whose methylation levels change with age across mammalian species. Genes associated with these cytosines are greatly enriched in mammalian developmental processes and implicated in age-associated diseases. From the methylation profiles of these age-related cytosines, we successfully constructed three highly accurate universal mammalian clocks for eutherians, and one universal clock for marsupials. The universal clocks for eutherians are similarly accurate for estimating ages (r>0.96) of any mammalian species and tissue with a single mathematical formula. Collectively, these new observations support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new and compelling evidence.

scholarly journals EPIGENETICS MARKERS OF AGING AND EXPOSURES

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.

scholarly journals A Systematic Review and Meta-analysis of Environmental, Lifestyle, and Health Factors Associated With DNA Methylation Age

2019 ◽  
Vol 75 (3) ◽  
pp. 481-494 ◽  
Author(s):  
Joanne Ryan ◽  
Jo Wrigglesworth ◽  
Jun Loong ◽  
Peter D Fransquet ◽  
Robyn L Woods
Keyword(s):  
Dna Methylation ◽  
Meta Analysis ◽  
Conclusive Evidence ◽  
Chronological Age ◽  
Biological Aging ◽  
Robust Estimate ◽  
Healthy Life ◽  
Age Related ◽  
Health Factors ◽  
Dna Methylation Age

Abstract DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an individual’s chronological age and can predict their risk of age-related disease and mortality. This study reviewed the evidence that environmental, lifestyle and health factors are associated with the Horvath and Hannum epigenetic clocks. A systematic search identified 61 studies. Chronological age was correlated with DNAm age in blood (median .83, range .13–.99). In a meta-analysis body mass index (BMI) was associated with increased DNAm age (Hannum β: 0.07, 95% CI 0.04 to 0.10; Horvath β: 0.06, 95% CI 0.02 to 0.10), but there was no association with smoking (Hannum β: 0.12, 95% CI −0.50 to 0.73; Horvath β:0.18, 95% CI −0.10 to 0.46). DNAm age was positively associated with frailty (three studies, n = 3,093), and education was negatively associated with the Hannum estimate of DNAm age specifically (four studies, n = 13,955). For most other exposures, findings were too inconsistent to draw conclusions. In conclusion, BMI was positively associated with biological aging measured using DNAm, with some evidence that frailty also increased aging. More research is needed to provide conclusive evidence regarding other exposures. This field of research has the potential to provide further insights into how to promote slower biological aging and ultimately prolong healthy life.

scholarly journals DNA methylation age and physical and cognitive ageing

2019 ◽  
Author(s):  
Jane Maddock ◽  
Juan Castillo-Fernandez ◽  
Andrew Wong ◽  
Rachel Cooper ◽  
Marcus Richards ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cognitive Performance ◽  
First Generation ◽  
Forced Expiratory Volume ◽  
Age Related ◽  
Dna Methylation Age ◽  
Speed Performance ◽  
One Year ◽  
Meta Analyses ◽  
Chair Rise

Abstract Background DNA methylation (DNAm) age acceleration (AgeAccel) has been shown to be predictive of all-cause mortality but it is unclear what functional aspect/s of ageing it captures. We examine associations between four measures of AgeAccel in adults aged 45-87 years and physical and cognitive performance and their age-related decline. Methods AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno and AgeAccelGrim were calculated in the Medical Research Council National Survey of Health and Development (NSHD), National Child Development Study (NCDS) and TwinsUK. Three measures of physical (grip strength, chair rise speed and forced expiratory volume in one second[FEV1]) and two measures of cognitive (episodic memory and mental speed) performance were assessed. Results AgeAccelPheno and AgeAccelGrim, but not AgeAccelHannum and AgeAccelHorvath were related to performance in random effects meta-analyses (n=1388-1685). For example, a one year increase in AgeAccelPheno/AgeAccelGrim was associated with a 0.01ml[95%CI:0.01,0.02]/0.03ml[95%CI:0.01,0.05] lower mean FEV1. In NSHD, AgeAccelPheno and AgeAccelGrim at 53 years were associated with age-related decline in performance between 53 and 69 years as tested by linear mixed models (p<0.05). In a subset of NSHD participants(n=482), there was little evidence that change in any AgeAccel measure was associated with change in performance conditional on baseline performance. Conclusions We found little evidence to support associations between the first generation of DNAm-based biomarkers of ageing and age-related physical or cognitive performance in mid-life to early old age. However, there was evidence that the second generation biomarkers, AgeAccelPheno and AgeAccelGrim, could act as makers of an individual’s health-span as proposed.

scholarly journals Universal DNA methylation age across mammalian tissues

2021 ◽  
Author(s):  
◽  
Ake T. Lu ◽  
Zhe Fei ◽  
Amin Haghani ◽  
Todd R. Robeck ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Aging Process ◽  
Mammalian Species ◽  
The Body ◽  
Cellular Damage ◽  
Developmental Processes ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Mammalian Tissues ◽  
Dna Methylation Age

ABSTRACTAging is often perceived as a degenerative process caused by random accrual of cellular damage over time. In spite of this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, it is difficult to ignore the likelihood that a defined and shared mechanism instead, underlies the aging process. To address this, we generated 10,000 methylation arrays, each profiling up to 37,000 cytosines in highly-conserved stretches of DNA, from over 59 tissue-types derived from 128 mammalian species. From these, we identified and characterized specific cytosines, whose methylation levels change with age across mammalian species. Genes associated with these cytosines are greatly enriched in mammalian developmental processes and implicated in age-associated diseases. From the methylation profiles of these age-related cytosines, we successfully constructed three highly accurate universal mammalian clocks for eutherians, and one universal clock for marsupials. The universal clocks for eutherians are similarly accurate for estimating ages (r>0.96) of any mammalian species and tissue with a single mathematical formula. Collectively, these new observations support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new and compelling evidence.

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

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.

scholarly journals The mediating effect of lifestyles on the association between social factors and DNA methylation

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Maugeri ◽  
M Barchitta ◽  
G Favara ◽  
C La Mastra ◽  
MC La Rosa ◽  
...  
Keyword(s):  
Physical Activity ◽  
Dna Methylation ◽  
Socioeconomic Status ◽  
Mediterranean Diet ◽  
Educational Level ◽  
Methylation Level ◽  
Mediating Effect ◽  
High Educational Level ◽  
Age Related ◽  
High Educational

Abstract Background Social disadvantage and unhealthy lifestyles may induce molecular changes associated with aging and age-related diseases. For instance, previous studies reported socioeconomic difference in DNA methylation, which in turn led to aberrant gene expression and genome instability. Socioeconomic status (SES) alone, however, does not completely explain this difference, and further studies are needed to unveil what factors contribute to it. Methods We conducted a cross-sectional study on 349 Italian women, aged 25-64 years, to assess SES differences in LINE-1 methylation level - a surrogate marker of global DNA methylation - and to examine the mediating effect of lifestyles (i.e. diet, smoking habits, physical activity, and weight status). Educational level was used as SES indicator. The adherence to Mediterranean diet (MD) was assessed by the Mediterranean Diet Score (MDS). Leukocyte LINE-1 methylation was assessed by pyrosequencing. Mediation analysis was conducted using the PROCESS macro for the SPSS software. Results We first observed that women with high educational level were more likely to be normal weight (p &lt; 0.001) and to adhere to MD (p = 0.018), and less likely to perform physical activity (p = 0.012) than their less educated counterpart. Moreover, age-adjusted linear regression demonstrated that LINE-1 methylation level increased with increasing educational level (β = 0.016; SE = 0.003; p &lt; 0.001). In line, mediation analysis demonstrated an indirect effect of high educational level on LINE-1 methylation through the adherence to MD (β = 0.003; 95%CI=0.001-0.006). Specifically, the mediator could account for 9.5% of the total effect. None of the other lifestyles, instead, exhibited a significant mediating effect. Conclusions To our knowledge, this is the first study demonstrating the mediation of diet in the relationship between SES and DNA methylation. Thus, our findings add even more value to the promotion of healthy dietary habits among social disadvantaged people. Key messages Social disadvantage is associated with epigenetic changes related to aging and age-related diseases. Adherence to the Mediterranean diet might mediate the association between socioeconomic status and DNA methylation.

scholarly journals Age Prediction of Human Based on DNA Methylation by Blood Tissues

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 870
Author(s):  
Jiansheng Zhang ◽  
Hongli Fu ◽  
Yan Xu
Keyword(s):  
Dna Methylation ◽  
Pearson Correlation ◽  
Close Correlation ◽  
Gradient Boosting ◽  
Tissue Samples ◽  
Regression Methods ◽  
Cpg Sites ◽  
Testing Dataset ◽  
Age Related ◽  
Better Than

In recent years, scientists have found a close correlation between DNA methylation and aging in epigenetics. With the in-depth research in the field of DNA methylation, researchers have established a quantitative statistical relationship to predict the individual ages. This work used human blood tissue samples to study the association between age and DNA methylation. We built two predictors based on healthy and disease data, respectively. For the health data, we retrieved a total of 1191 samples from four previous reports. By calculating the Pearson correlation coefficient between age and DNA methylation values, 111 age-related CpG sites were selected. Gradient boosting regression was utilized to build the predictive model and obtained the R2 value of 0.86 and MAD of 3.90 years on testing dataset, which were better than other four regression methods as well as Horvath’s results. For the disease data, 354 rheumatoid arthritis samples were retrieved from a previous study. Then, 45 CpG sites were selected to build the predictor and the corresponded MAD and R2 were 3.11 years and 0.89 on the testing dataset respectively, which showed the robustness of our predictor. Our results were better than the ones from other four regression methods. Finally, we also analyzed the twenty-four common CpG sites in both healthy and disease datasets which illustrated the functional relevance of the selected CpG sites.

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