scholarly journals Dysfunctional epigenetic aging of the normal colon and colorectal cancer risk

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Ting Wang ◽  
Sean K. Maden ◽  
Georg E. Luebeck ◽  
Christopher I. Li ◽  
Polly A. Newcomb ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Risk Group ◽  
Risk Groups ◽  
Biological Age ◽  
Chronological Age ◽  
Epigenetic Clock ◽  
Normal Colon ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration

Abstract Background Chronological age is a prominent risk factor for many types of cancers including colorectal cancer (CRC). Yet, the risk of CRC varies substantially between individuals, even within the same age group, which may reflect heterogeneity in biological tissue aging between people. Epigenetic clocks based on DNA methylation are a useful measure of the biological aging process with the potential to serve as a biomarker of an individual’s susceptibility to age-related diseases such as CRC. Methods We conducted a genome-wide DNA methylation study on samples of normal colon mucosa (N = 334). Subjects were assigned to three cancer risk groups (low, medium, and high) based on their personal adenoma or cancer history. Using previously established epigenetic clocks (Hannum, Horvath, PhenoAge, and EpiTOC), we estimated the biological age of each sample and assessed for epigenetic age acceleration in the samples by regressing the estimated biological age on the individual’s chronological age. We compared the epigenetic age acceleration between different risk groups using a multivariate linear regression model with the adjustment for gender and cell-type fractions for each epigenetic clock. An epigenome-wide association study (EWAS) was performed to identify differential methylation changes associated with CRC risk. Results Each epigenetic clock was significantly correlated with the chronological age of the subjects, and the Horvath clock exhibited the strongest correlation in all risk groups (r > 0.8, p < 1 × 10−30). The PhenoAge clock (p = 0.0012) revealed epigenetic age deceleration in the high-risk group compared to the low-risk group. Conclusions Among the four DNA methylation-based measures of biological age, the Horvath clock is the most accurate for estimating the chronological age of individuals. Individuals with a high risk for CRC have epigenetic age deceleration in their normal colons measured by the PhenoAge clock, which may reflect a dysfunctional epigenetic aging process.

scholarly journals Alcohol consumption and methylation-based measures of biological age

2021 ◽  
Author(s):  
Jacob K Kresovich ◽  
Alexandra M Martinez Lopez ◽  
Emma L Garval ◽  
Zongli Xu ◽  
Alexandra J White ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Consumption ◽  
Biological Age ◽  
Average Lifetime ◽  
Epigenetic Clock ◽  
Genome Wide ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
The Mean ◽  
Average Consumption

Abstract Epigenetic age acceleration is considered a measure of biological aging based on genome-wide patterns of DNA methylation. Although age acceleration has been associated with incidence of diseases and death, less is known about how it is related to lifestyle behaviors. Among 2,316 women, we evaluate associations between self-reported alcohol consumption and various metrics of epigenetic age acceleration. Recent average alcohol consumption was defined as the mean number of drinks consumed per week within the past year; lifetime average consumption was estimated as the mean number of drinks per year drinking. Whole blood genome-wide DNA methylation was measured with HumanMethylation450 BeadChips and used to assess four epigenetic clocks (Hannum, Horvath, PhenoAge, GrimAge) and their corresponding metrics of epigenetic age acceleration (Hannum AgeAccel, Horvath AgeAccel, PhenoAgeAccel, GrimAgeAccel). Although alcohol consumption showed little association with most age acceleration metrics, both lifetime and recent average consumption measures were positively associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: β=0.30 years, 95% CI: 0.11, 0.48, p=0.002; recent, per additional 5 drinks/week: β=0.19 years, 95% CI: 0.01, 0.37, p=0.04). In a mutually adjusted model, only average lifetime alcohol consumption remained associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: β=0.27 years, 95% CI: 0.04, 0.50, p=0.02; recent, per 5 additional drinks/week: β=0.05 years, 95% CI: -0.16, 0.26, p=0.64). Although alcohol use does not appear to be strongly associated with biological age measured by most epigenetic clocks, lifetime average consumption is associated with higher biological age assessed by the GrimAge epigenetic clock.

scholarly journals The aging DNA methylome reveals environment-by-aging interactions in a model teleost

2021 ◽  
Author(s):  
Emily M Bertucci ◽  
Marilyn W Mason ◽  
Olin E Rhodes ◽  
Benjamin B Parrott
Keyword(s):  
Dna Methylation ◽  
Environmental Factors ◽  
Environmental Drivers ◽  
Chronological Age ◽  
Epigenetic Clock ◽  
Ongoing Research ◽  
Dna Methylome ◽  
Age Related ◽  
Epigenetic Aging ◽  
Epigenetic Age

The rate at which individuals age underlies variation in life history and attendant health and disease trajectories. Age specific patterning of the DNA methylome (epigenetic aging) is strongly correlated with chronological age in humans and can be modeled to produce epigenetic age predictors. However, epigenetic age estimates vary among individuals of the same age, and this mismatch is correlated to the onset of age-related disease and all-cause mortality. Yet, the origins of epigenetic-to-chronological age discordance are not resolved. In an effort to develop a tractable model in which environmental drivers of epigenetic aging can be assessed, we investigate the relationship between aging and DNA methylation in a small teleost, medaka (Oryzias latipes). We find that age-associated DNA methylation patterning occurs broadly across the genome, with the majority of age-related changes occurring during early life. By modeling the stereotypical nature of age-associated DNA methylation dynamics, we built an epigenetic clock, which predicts chronological age with a mean error of 29.1 days (~4% of average lifespan). Characterization of clock loci suggests that aspects of epigenetic aging are functionally similar across vertebrates. To understand how environmental factors interact with epigenetic aging, we exposed medaka to four doses of ionizing radiation for seven weeks, hypothesizing that exposure to such an environmental stressor would accelerate epigenetic aging. While the epigenetic clock was not significantly affected, radiation exposure accelerated and decelerated patterns of normal epigenetic aging, with radiation-induced epigenetic alterations enriched at loci that become hypermethylated with age. Together, our findings advance ongoing research attempting to elucidate the functional role of DNA methylation in integrating environmental factors into the rate of biological aging.

Abstract P106: Epigenetic Age Acceleration and Postprandial Lipemia in the Genetics of Lipid Lowering Drugs and Diet Network Study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Marguerite R Irvin ◽  
Bertha Hidalgo ◽  
Degui Zhi ◽  
Stella Aslibekyan ◽  
Hemant K Tiwari ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cell ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Chronological Age ◽  
Lipid Levels ◽  
Lipid Lowering Drugs ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration

Background: Calculated ‘epigenetic age,’ a novel biomarker based on DNA methylation levels of 353 CpGs, has been demonstrated to accurately predict chronological age across a broad spectrum of tissues and cell types. Recently epigenetic age acceleration or older epigenetic age in comparison to chronological age has been robustly associated with all-cause mortality independent of chronological age in multiple human cohorts. However, accelerated epigenetic aging has not been associated with lipids levels, including postprandial lipid levels which are linked to prothrombotic and proinflammatory processes that may precipitate aging. In the current study we aimed to evaluate the association between epigenetic age acceleration and lipid levels. Methods: We used the Horvath DNA methylation age calculator to estimate epigenetic age in 988 Caucasian participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) using Illumina Infinium HumanMethylation450 BeadChip array data derived from CD4+ T-cell DNA. GOLDN participants did not take lipid lowering drugs for at least four weeks prior to enrollment and underwent a standardized high fat meal challenge after fasting for at least 8 hours followed by timed blood draws at 3.5 and 6 hours following the meal. Epigenetic age acceleration was calculated as the residual from regressing methylation age on chronological age. We used linear mixed models to examine the association of age acceleration quartiles with fasting and postrandial (3.5 and 6 hour time points) low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG) levels after adjusting for age, study site, sex, fasting lipid level (if applicable), deconvolution estimated T-cell type percentages and a random effect of family relationship. Results: The correlation between calculated methylation age and chronological age was 0.91. The difference between methylation age and chronological age (methylation age - chronological age) was on average -5.8 (5.9), -0.5 (4.7), 2.9 (4.3), and 7.8 (5.0) years for the first through fourth quartiles of age acceleration, respectively. After adjustment for covariates neither fasting nor postprandial lipids were associated with age acceleration quartile. Conclusions: Evidence from the current study suggests lipid levels in the fasting and postprandial state are not related to accelerated epigenetic aging, however given the association between epigenetic age acceleration and mortality observed in previous studies the relationship of other metabolic parameters with age acceleration may be worthy of investigation.

scholarly journals Racial Disparities in Epigenetic Aging of the Right vs Left Colon

2020 ◽  
Author(s):  
Matthew Devall ◽  
Xiangqing Sun ◽  
Fangcheng Yuan ◽  
Gregory S Cooper ◽  
Joseph Willis ◽  
...  
Keyword(s):  
Dna Methylation ◽  
African Americans ◽  
Racial Differences ◽  
Age Of Onset ◽  
Left Colon ◽  
Right Colon ◽  
Normal Colon ◽  
Epigenetic Aging ◽  
Epigenetic Age Acceleration ◽  
The Right

Abstract There are well-documented racial differences in age-of-onset and laterality of colorectal cancer. Epigenetic age acceleration is postulated to be an underlying factor. However, comparative studies of side-specific colonic tissue epigenetic aging are lacking. Here, we performed DNA methylation analysis of matched right and left biopsies of normal colon from 128 individuals. Among African Americans (n = 88), the right colon showed accelerated epigenetic aging as compared to individual-matched left colon (1.51 years; 95% CI = 0.62 to 2.40 years; two-sided P = .001). In contrast, among European Americans (n = 40), the right colon shows remarkable age deceleration (1.93 years; 95% CI = 0.65 to 3.21 years; two-sided P = .004). Further, epigenome-wide analysis of DNA methylation identifies a unique pattern of hypermethylation in African American right colon. Our study is the first to report such race and side-specific differences in epigenetic aging of normal colon, providing novel insight into the observed younger age-of-onset and relative preponderance of right-side colon neoplasia in African Americans.

scholarly journals Epigenetic clock and DNA methylation studies of roe deer in the wild

2020 ◽  
Author(s):  
Jean-François Lemaître ◽  
Benjamin Rey ◽  
Jean-Michel Gaillard ◽  
Corinne Régis ◽  
Emmanuelle Gilot ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Evolutionary Biology ◽  
Roe Deer ◽  
Chronological Age ◽  
Epigenetic Clock ◽  
Aging Effects ◽  
Methylation Array ◽  
Biomarkers Of Aging ◽  
Epigenetic Age ◽  
The Relationship

AbstractDNA methylation-based biomarkers of aging (epigenetic clocks) promise to lead to new insights in the evolutionary biology of ageing. Relatively little is known about how the natural environment affects epigenetic aging effects in wild species. In this study, we took advantage of a unique long-term (>40 years) longitudinal monitoring of individual roe deer (Capreolus capreolus) living in two wild populations (Chizé and Trois Fontaines, France) facing different ecological contexts to investigate the relationship between chronological age and levels of DNA methylation (DNAm). We generated novel DNA methylation data from n=90 blood samples using a custom methylation array (HorvathMammalMethylChip40). We present three DNA methylation-based estimators of age (DNAm or epigenetic age), which were trained in males, females, and both sexes combined. We investigated how sex differences influenced the relationship between DNAm age and chronological age through the use of sex-specific epigenetic clocks. Our results highlight that both populations and sex influence the epigenetic age, with the bias toward a stronger male average age acceleration (i.e. differences between epigenetic age and chronological ages) particularly pronounced in the population facing harsh environmental conditions. Further, we identify the main sites of epigenetic alteration that have distinct aging patterns across the two sexes. These findings open the door to promising avenues of research at the crossroad of evolutionary biology and biogerontology.

scholarly journals Exploring Epigenetic Age in Response to Intensive Relaxing Training: A Pilot Study to Slow Down Biological Age

2019 ◽  
Vol 16 (17) ◽  
pp. 3074 ◽  
Author(s):  
Pavanello ◽  
Campisi ◽  
Tona ◽  
Lin ◽  
Iliceto
Keyword(s):  
Myocardial Infarction ◽  
Age Estimation ◽  
Healthy Subjects ◽  
Molecular Mechanisms ◽  
Biological Age ◽  
Chronological Age ◽  
Biological Aging ◽  
Epigenetic Clock ◽  
Age Related ◽  
Epigenetic Age

DNA methylation (DNAm) is an emerging estimator of biological aging, i.e., the often-defined “epigenetic clock”, with a unique accuracy for chronological age estimation (DNAmAge). In this pilot longitudinal study, we examine the hypothesis that intensive relaxing training of 60 days in patients after myocardial infarction and in healthy subjects may influence leucocyte DNAmAge by turning back the epigenetic clock. Moreover, we compare DNAmAge with another mechanism of biological age, leucocyte telomere length (LTL) and telomerase. DNAmAge is reduced after training in healthy subjects (p = 0.053), but not in patients. LTL is preserved after intervention in healthy subjects, while it continues to decrease in patients (p = 0.051). The conventional negative correlation between LTL and chronological age becomes positive after training in both patients (p < 0.01) and healthy subjects (p < 0.05). In our subjects, DNAmAge is not associated with LTL. Our findings would suggest that intensive relaxing practices influence different aging molecular mechanisms, i.e., DNAmAge and LTL, with a rejuvenating effect. Our study reveals that DNAmAge may represent an accurate tool to measure the effectiveness of lifestyle-based interventions in the prevention of age-related diseases.

scholarly journals Exploring the Relationship of Relative Telomere Length and the Epigenetic Clock in the LipidCardio Cohort

2019 ◽  
Vol 20 (12) ◽  
pp. 3032 ◽  
Author(s):  
Verena L. Banszerus ◽  
Valentin M. Vetter ◽  
Bastian Salewsky ◽  
Maximilian König ◽  
Ilja Demuth
Keyword(s):  
Telomere Length ◽  
Penalized Regression ◽  
Biological Age ◽  
Chronological Age ◽  
Epigenetic Clock ◽  
Single Nucleotide ◽  
Epigenetic Age ◽  
High Prevalence ◽  
Relationship Of ◽  
The Relationship

Telomere length has been accepted widely as a biomarker of aging. Recently, a novel candidate biomarker has been suggested to predict an individual’s chronological age with high accuracy: The epigenetic clock is based on the weighted DNA methylation (DNAm) fraction of a number of cytosine-phosphate-guanine sites (CpGs) selected by penalized regression analysis. Here, an established methylation-sensitive single nucleotide primer extension method was adapted, to estimate the epigenetic age of the 1005 participants of the LipidCardio Study, a patient cohort characterised by high prevalence of cardiovascular disease, based on a seven CpGs epigenetic clock. Furthermore, we measured relative leukocyte telomere length (rLTL) to assess the relationship between the established and the promising new measure of biological age. Both rLTL (0.79 ± 0.14) and DNAm age (69.67 ± 7.27 years) were available for 773 subjects (31.6% female; mean chronological age= 69.68 ± 11.01 years; mean DNAm age acceleration = −0.01 ± 7.83 years). While we detected a significant correlation between chronological age and DNAm age (n = 779, R = 0.69), we found neither evidence of an association between rLTL and the DNAm age (β = 3.00, p = 0.18) nor rLTL and the DNAm age acceleration (β = 2.76, p = 0.22) in the studied cohort, suggesting that DNAm age and rLTL measure different aspects of biological age.

scholarly journals Pair bonding slows epigenetic aging and alters methylation in brains of prairie voles

2020 ◽  
Author(s):  
Lindsay L. Sailer ◽  
Amin Haghani ◽  
Joseph A. Zoller ◽  
Caesar Z. Li ◽  
Alexander G. Ophir ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Tissue ◽  
Association Studies ◽  
Chronological Age ◽  
Epigenetic Clock ◽  
Pair Bonding ◽  
Prairie Voles ◽  
Relative Age ◽  
Biomarkers Of Aging ◽  
Epigenetic Aging

ABSTRACTThe quality of romantic relationships can be predictive of health consequences related to aging. DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how pair bonding impacts aging. Prairie voles (Microtus ochrogaster) have emerged as a model to study social attachment among adult pairs. Here we describe DNA methylation-based estimators of age for prairie voles based on novel DNA methylation data generated on highly conserved mammalian CpGs measured with a custom array. The multi-tissue epigenetic clock for voles was trained on 3 tissue sources (ear, liver, and samples of brain tissue from within the pair bonding circuit). A novel dual species human-vole clock accurately measured relative age defined as the ratio of chronological age to maximum age. According to the human-vole clock of relative age, sexually inexperienced voles exhibit accelerated epigenetic aging in brain tissue (p = 0.02) when compared to pair bonded animals of the same chronological age. Epigenome wide association studies identified CpGs in four genes that were strongly associated with pair bonding across the three tissue types (brain, ear, and liver): Hnrnph1, Fancl, Fam13b, and Fzd1. Further, four CpGs (near the Bmp4 exon, Eif4g2 3 prime UTR, Robo1 exon, and Nfat5 intron) exhibited a convergent methylation change between pair bonding and aging. This study describes highly accurate DNA methylation-based estimators of age in prairie voles and provides evidence that pair bonding status modulates the methylome.

scholarly journals Epigenetic Age Acceleration of Stomach Adenocarcinoma Associated With Tumor Stemness Features, Immunoactivation, and Favorable Prognosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunhong Hong ◽  
Shaohua Yang ◽  
Qiaojin Wang ◽  
Shiqiang Zhang ◽  
Wenhui Wu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Correlation Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Chronological Age ◽  
Favorable Prognosis ◽  
Molecular Features ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
Stomach Adenocarcinoma

Background: Abnormal DNA methylation (DNAm) age has been assumed to be an indicator for canceration and all-cause mortality. However, associations between DNAm age and molecular features of stomach adenocarcinoma (STAD), and its prognosis have not been systematically studied.Method: We calculated the DNAm age of 591 STAD samples and 115 normal stomach samples from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) database using the Horvath’s clock model. Meanwhile, we utilized survival analysis to evaluate the prognostic value of DNAm age and epigenetic age acceleration shift. In addition, we performed weighted gene co-expression network analysis (WGCNA) to identify DNAm age-associated gene modules and pathways. Finally, the association between DNAm age and molecular features was performed by correlation analysis.Results: DNA methylation age was significantly correlated with chronological age in normal gastric tissues (r = 0.85, p &lt; 0.0001), but it was not associated with chronological age in STAD samples (r = 0.060, p = 0.2369). Compared with tumor adjacent normal tissue, the DNAm age of STAD tissues was significantly decreased. Meanwhile, chronological age in STAD samples was higher than its DNAm age. Both DNAm age and epigenetic acceleration shift were associated with the prognosis of STAD patients. By using correlation analysis, we also found that DNAm age was associated with immunoactivation and stemness in STAD samples.Conclusion: In summary, epigenetic age acceleration of STAD was associated with tumor stemness, immunoactivation, and favorable prognosis.

scholarly journals The combined effect of obesity and aging on human sperm DNA methylation signatures: inclusion of BMI in the paternal germ line age prediction model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Albert Salas-Huetos ◽  
Emma R. James ◽  
Dallin S. Broberg ◽  
Kenneth I. Aston ◽  
Douglas T. Carrell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Line ◽  
Age Groups ◽  
Human Sperm ◽  
Absolute Error ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Sperm Dna ◽  
Epigenetic Age Acceleration ◽  
The Impact

Abstract Male aging and obesity have both been shown to contribute to declines in fertility in men. Recent work in aging has shown consistent epigenetic changes to sperm as a man ages. In fact, our lab has built a tool that utilizes DNA methylation signatures from sperm to effectively predict an individual’s age. Herein, we performed this preliminary cohort study to determine if increased BMI accelerates the epigenetic aging in sperm. A total of 96 participants were divided into four age groups (22–24, 30, 40–41, and > 48 years of age) and additionally parsed into two BMI sub-categories (normal and high/obese). We found no statistically significant epigenetic age acceleration. However, it is important to note that within each age category, high BMI individuals were predicted to be older on average than their actual age (~ 1.4 years), which was not observed in the normal BMI group. To further investigate this, we re-trained a model using only the present data with and without BMI as a feature. We found a modest but non-significant improvement in prediction with BMI [r2 = 0.8814, mean absolute error (MAE) = 3.2913] compared to prediction without BMI (r2 = 0.8739, MAE = 3.3567). Future studies with higher numbers of age-matched individuals are needed to definitively understand the impact of BMI on epigenetic aging in sperm.

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