Associations of Alcohol Consumption With Epigenome‐Wide DNA Methylation and Epigenetic Age Acceleration: Individual‐Level and Co‐twin Comparison Analyses

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.

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Association of cardiovascular health and epigenetic age acceleration

Clinical Epigenetics ◽

10.1186/s13148-021-01028-2 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Tess D. Pottinger ◽

Sadiya S. Khan ◽

Yinan Zheng ◽

Wei Zhang ◽

Hilary A. Tindle ◽

...

Keyword(s):

Dna Methylation ◽

Cardiovascular Health ◽

Heart Association ◽

The United States ◽

Cross Sectional ◽

Epigenetic Age ◽

Younger Age ◽

Cardiovascular Morbidity And Mortality ◽

Epigenetic Age Acceleration ◽

Linear Regression Modeling

Abstract Background Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the “Life’s Simple 7” ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality. However, it is unknown whether poor CVH is associated with acceleration of aging as measured by DNA methylation markers in epigenetic age. Methods and results We performed a cross-sectional analysis of racially/ethnically diverse post-menopausal women enrolled in the Women’s Health Initiative cohort recruited between 1993 and 1998. Epigenetic age acceleration (EAA) was calculated using DNA methylation data on a subset of participants and the published Horvath and Hannum methods for intrinsic and extrinsic EAA. CVH was calculated using the AHA measures of CVH contributing to a 7-point score. We examined the association between CVH score and EAA using linear regression modeling adjusting for self-reported race/ethnicity and education. Among the 2,170 participants analyzed, 50% were white and mean age was 64 (7 SD) years. Higher or more favorable CVH scores were associated with lower extrinsic EAA (~ 6 months younger age per 1 point higher CVH score, p < 0.0001), and lower intrinsic EAA (3 months younger age per 1 point higher CVH score, p < 0.028). Conclusions These cross-sectional observations suggest a possible mechanism by which ideal CVH is associated with greater longevity.

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Accelerated Epigenetic Age in Normal Cognitive Aging of Korean Community-Dwelling Older Adults

Biological Research For Nursing ◽

10.1177/1099800420983896 ◽

2021 ◽

pp. 109980042098389

Author(s):

Jongmin Park ◽

Chang Won Won ◽

Leorey N. Saligan ◽

Youn-Jung Kim ◽

Yoonju Kim ◽

...

Keyword(s):

Older Adults ◽

Dna Methylation ◽

Cognitive Function ◽

Cognitive Aging ◽

Community Dwelling ◽

Test Results ◽

Cohen’S D ◽

Epigenetic Age ◽

Epigenetic Age Acceleration ◽

Community Dwelling Older Adults

Background: Epigenetic age acceleration has been studied as a promising biomarker of age-related conditions, including cognitive aging. This pilot study aims to explore potential cognitive aging-related biomarkers by investigating the relationship of epigenetic age acceleration and cognitive function and by examining the epigenetic age acceleration differences between successful cognitive aging (SCA) and normal cognitive aging (NCA) among Korean community-dwelling older adults (CDOAs). Methods: We used data and blood samples of Korean CDOAs from the Korean Frailty and Aging Cohort Study. The participants were classified into two groups, SCA (above the 50th percentile in all domains of cognitive function) and NCA. The genome-wide DNA methylation profiling array using Illumina Infinium MethylationEPIC BeadChip was used to calculate the following: the DNA methylation age, universal epigenetic age acceleration, intrinsic epigenetic age acceleration (IEAA), and extrinsic epigenetic age acceleration (EEAA). We also used Pearson correlation analysis and independent t-tests to analyze the data. Results: Universal age acceleration correlated with the Frontal Assessment Battery test results ( r = −0.42, p = 0.025); the EEAA correlated with the Word List Recognition test results ( r = −0.41, p = 0.027). There was a significant difference between SCA and NCA groups in IEAA ( p = 0.041, Cohen’s d = 0.82) and EEAA ( p = 0.042, Cohen’s d = 0.78). Conclusions: Epigenetic age acceleration can be used as a biomarker for early detection of cognitive decline in Korean community-dwelling older adults. Large longitudinal studies are warranted.

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Epigenetic Age Acceleration and Hearing: Observations From the Baltimore Longitudinal Study of Aging

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.790926 ◽

2021 ◽

Vol 13 ◽

Author(s):

Pei-Lun Kuo ◽

Ann Zenobia Moore ◽

Frank R. Lin ◽

Luigi Ferrucci

Keyword(s):

Dna Methylation ◽

Longitudinal Study ◽

Smoking History ◽

Future Research ◽

Age Related ◽

Epigenetic Age ◽

Epigenetic Age Acceleration ◽

Baltimore Longitudinal Study ◽

Age Related Hearing Loss ◽

The Relationship

Objectives: Age-related hearing loss (ARHL) is highly prevalent among older adults, but the potential mechanisms and predictive markers for ARHL are lacking. Epigenetic age acceleration has been shown to be predictive of many age-associated diseases and mortality. However, the association between epigenetic age acceleration and hearing remains unknown. Our study aims to investigate the relationship between epigenetic age acceleration and audiometric hearing in the Baltimore Longitudinal Study of Aging (BLSA).Methods: Participants with both DNA methylation and audiometric hearing measurements were included. The main independent variables are epigenetic age acceleration measures, including intrinsic epigenetic age acceleration—“IEAA,” Hannum age acceleration—“AgeAccelerationResidualHannum,” PhenoAge acceleration—“AgeAccelPheno,” GrimAge acceleration—“AgeAccelGrim,” and methylation-based pace of aging estimation—“DunedinPoAm.” The main dependent variable is speech-frequency pure tone average. Linear regression was used to assess the association between epigenetic age acceleration and hearing.Results: Among the 236 participants (52.5% female), after adjusting for age, sex, race, time difference between measurements, cardiovascular factors, and smoking history, the effect sizes were 0.11 995% CI: (–0.00, 0.23), p = 0.054] for Hannum’s clock, 0.08 [95% CI: (–0.03, 0.19), p = 0.143] for Horvath’s clock, 0.10 [95% CI: (–0.01, 0.21), p = 0.089] for PhenoAge, 0.20 [95% CI: (0.06, 0.33), p = 0.004] for GrimAge, and 0.21 [95% CI: (0.09, 0.33), p = 0.001] for DunedinPoAm.Discussion: The present study suggests that some epigenetic age acceleration measurements are associated with hearing. Future research is needed to study the potential subclinical cardiovascular causes of hearing and to investigate the longitudinal relationship between DNA methylation and hearing.

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Intrinsic and extrinsic epigenetic age acceleration are associated with hypertensive target organ damage in older African Americans

BMC Medical Genomics ◽

10.1186/s12920-019-0585-5 ◽

2019 ◽

Vol 12 (1) ◽

Author(s):

Jennifer A. Smith ◽

Jeremy Raisky ◽

Scott M. Ratliff ◽

Jiaxuan Liu ◽

Sharon L. R. Kardia ◽

...

Keyword(s):

Blood Pressure ◽

Dna Methylation ◽

African Americans ◽

Target Organ Damage ◽

Organ Damage ◽

Left Ventricular ◽

Effect Modification ◽

Target Organ ◽

Epigenetic Age ◽

Epigenetic Age Acceleration

Abstract Background Epigenetic age acceleration, a measure of biological aging based on DNA methylation, is associated with cardiovascular mortality. However, little is known about its relationship with hypertensive target organ damage to the heart, kidneys, brain, and peripheral arteries. Methods We investigated associations between intrinsic (IEAA) or extrinsic (EEAA) epigenetic age acceleration, blood pressure, and six types of organ damage in a primarily hypertensive cohort of 1390 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. DNA methylation from peripheral blood leukocytes was collected at baseline (1996–2000), and measures of target organ damage were assessed in a follow-up visit (2000–2004). Linear regression with generalized estimating equations was used to test for associations between epigenetic age acceleration and target organ damage, as well as effect modification of epigenetic age by blood pressure or sex. Sequential Oligogenic Linkage Analysis Routines (SOLAR) was used to test for evidence of shared genetic and/or environmental effects between epigenetic age acceleration and organ damage pairs that were significantly associated. Results After adjustment for sex, chronological age, and time between methylation and organ damage measures, higher IEAA was associated with higher urine albumin to creatinine ratio (UACR, p = 0.004), relative wall thickness (RWT, p = 0.022), and left ventricular mass index (LVMI, p = 0.007), and with lower ankle-brachial index (ABI, p = 0.014). EEAA was associated with higher LVMI (p = 0.005). Target organ damage associations for all but IEAA with LVMI remained significant after further adjustment for blood pressure and antihypertensive use (p < 0.05). Further adjustment for diabetes attenuated the IEAA associations with UACR and RWT, and adjustment for smoking attenuated the IEAA association with ABI. No effect modification by age or sex was observed. Conclusions Measures of epigenetic age acceleration may help to better characterize the functional mechanisms underlying organ damage from cellular aging and/or hypertension. These measures may act as subclinical biomarkers for damage to the kidney, heart, and peripheral vasculature; however more research is needed to determine whether these relationships remain independent of lifestyle factors and comorbidities.

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Reproductive history and blood cell DNA methylation later in life: the Young Finns Study

Clinical Epigenetics ◽

10.1186/s13148-021-01215-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Emily W. Harville ◽

Pashupati P. Mishra ◽

Mika Kähönen ◽

Emma Raitoharju ◽

Saara Marttila ◽

...

Keyword(s):

Dna Methylation ◽

Reproductive History ◽

Hypertensive Disorders Of Pregnancy ◽

Birth Registry ◽

Hypertensive Disorders ◽

Epigenetic Age ◽

Epigenetic Age Acceleration ◽

Epigenetic Methylation ◽

History Of ◽

Young Finns Study

Abstract Background Women with a history of complications of pregnancy, including hypertensive disorders, gestational diabetes or an infant fetal growth restriction or preterm birth, are at higher risk for cardiovascular disease later in life. We aimed to examine differences in maternal DNA methylation following pregnancy complications. Methods Data on women participating in the Young Finns study (n = 836) were linked to the national birth registry. DNA methylation in whole blood was assessed using the Infinium Methylation EPIC BeadChip. Epigenome-wide analysis was conducted on differential CpG methylation at 850 K sites. Reproductive history was also modeled as a predictor of four epigenetic age indices. Results Fourteen significant differentially methylated sites were found associated with both history of pre-eclampsia and overall hypertensive disorders of pregnancy. No associations were found between reproductive history and any epigenetic age acceleration measure. Conclusions Differences in epigenetic methylation profiles could represent pre-existing risk factors, or changes that occurred as a result of experiencing these complications.

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

Frontiers in Genetics ◽

10.3389/fgene.2021.563051 ◽

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 < 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.

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

Scientific Reports ◽

10.1038/s41598-020-71979-8 ◽

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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Different epigenetic clocks reflect distinct pathophysiological features of multiple sclerosis

Epigenomics ◽

10.2217/epi-2019-0102 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1429-1439 ◽

Cited By ~ 1

Author(s):

Eleftheria Theodoropoulou ◽

Lars Alfredsson ◽

Fredrik Piehl ◽

Francesco Marabita ◽

Maja Jagodic

Keyword(s):

Multiple Sclerosis ◽

Dna Methylation ◽

Positive Association ◽

Cell Types ◽

Gene Expression Omnibus ◽

Methylation Data ◽

Accession Number ◽

Age Related ◽

Epigenetic Age ◽

Epigenetic Age Acceleration

Aim: Accumulating evidence links epigenetic age to diseases and age-related conditions, but little is known about its association with multiple sclerosis (MS). Materials & methods: We estimated epigenetic age acceleration measures using DNA methylation from blood or sorted cells of MS patients and controls. Results: In blood, sex (p = 4.39E-05) and MS (p = 2.99E-03) explained the variation in age acceleration, and isolated blood cell types showed different epigenetic age. Intrinsic epigenetic age acceleration and extrinsic epigenetic age acceleration were only associated with sex (p = 2.52E-03 and p = 1.58E-04, respectively), while PhenoAge Acceleration displayed positive association with MS (p = 3.40E-02). Conclusion: Different age acceleration measures are distinctly influenced by phenotypic factors, and they might measure separate pathophysiological aspects of MS. Data deposition: DNA methylation data can be accessed at Gene Expression Omnibus database under accession number GSE35069, GSE43976, GSE106648, GSE130029, GSE130030.

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