Epigenetic Age Acceleration and Change in Frailty in MOBILIZE Boston

2022 ◽  
Author(s):  
Benjamin Seligman ◽  
Sarah D Berry ◽  
Lewis A Lipsitz ◽  
Thomas G Travison ◽  
Douglas P Kiel
Keyword(s):  
Dna Methylation ◽  
Smoking Status ◽  
Frailty Index ◽  
450K Array ◽  
Frailty Phenotype ◽  
Cross Sectional ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
Frailty Score

Abstract Age-associated changes in DNA methylation have been implicated as one mechanism to explain the development of frailty, however previous cross-sectional studies of epigenetic age acceleration (eAA) and frailty have had inconsistent findings. Few longitudinal studies have considered the association of eAA with change in frailty. We sought to determine the association between eAA and change in frailty in the MOBILIZE Boston cohort. Participants were assessed at two visits 12-18 months apart. Intrinsic, extrinsic, GrimAge, and PhenoAge eAA were assessed from whole blood DNA methylation at baseline using the Infinium 450k array. Frailty was assessed by a continuous frailty score based on the frailty phenotype and by frailty index (FI). Analysis was by correlation and linear regression with adjustment for age, sex, smoking status, and BMI. 395 participants with a frailty score and 431 with a FI had epigenetic and follow-up frailty measures. For the frailty score and FI cohorts, respectively, mean (SD) ages were 77.8 (5.49) and 77.9 (5.47), 232 (58.7%) and 257 (59.6%) were female. All participants with epigenetic data identified as white. Baseline frailty score was not correlated with intrinsic or extrinsic eAA, but was correlated with PhenoAge and, even after adjustment for covariates, GrimAge. Baseline FI was correlated with extrinsic, GrimAge, and PhenoAge eAA with and without adjustment. No eAA measure was associated with change in frailty, with or without adjustment. Our results suggest that no eAA measure was associated with change in frailty. Further studies should consider longer periods of follow-up and repeated eAA measurement.

scholarly journals Association of cardiovascular health and epigenetic age acceleration

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.

Abstract MP26: Obesity is Associated With Accelerated Epigenetic Aging in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Sadiya S Khan ◽  
Yinan Zheng ◽  
Laura A Colangelo ◽  
Wei Zhang ◽  
Cora E Lewis ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Sex Education ◽  
Smoking Status ◽  
Accelerated Aging ◽  
Intermediate Phenotype ◽  
Age Related ◽  
Epigenetic Age ◽  
Increased Risk ◽  
Epigenetic Age Acceleration ◽  
Biomarker Of Aging

Background: Obesity is associated with increased risk of cardiovascular and other age-related diseases that may represent accelerated aging. As methylation levels in DNA change with aging, epigenetic age (EA), which integrates whole-genome methylation has emerged as a novel biomarker of aging and has been associated with mortality and age-related morbidity. Epigenetic age acceleration (EAA), is based on the residual value of 353 previously defined methylation markers regressed on chronologic age (CA), and is thus independent of CA. Therefore, we sought to examine the association of obesity and EAA in midlife. Methods: A subset of participants in the CARDIA cohort (n=1200) randomly selected (balanced on race and sex) underwent genome-wide DNA methylation profiling with the Illumina EPIC array from exam year 15 (2000-01 [age 33-45 years]) and 20 (2005-06 [38-50 years] for calculation of EAA. Body mass index (BMI) was measured at Y15 and Y20, respectively. We used linear regression to examine the association of obesity (independent variable) with EAA after adjusting for CA, race, sex, education, study center, smoking status, physical activity, and alcohol intake. Results: Participants were 52% female and 41% black and had mean BMI 28.5±6.2 kg/m 2 at Y15 and 29.2±6.4 kg/m 2 at Y20. At Y15, participants who were obese had 1.04 (0.38) years higher EAA compared to normal BMI participants (p<0.01, Figure) . Similar results were observed at Y20. Results were similar when evaluating the association of BMI continuously with EAA (p<0.05). Conclusions: EAA is a promising molecular biomarker of aging associated with obesity. Changes in DNA methylation may serve as an intermediate phenotype prior to the onset of age-associated pathologies related to obesity.

scholarly journals Associations Between Blood Pressure and Accelerated DNA Methylation Aging

2022 ◽  
Author(s):  
Lili Xiao ◽  
Gaohui Zan ◽  
Chaoqun Liu ◽  
Xia Xu ◽  
Longman Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dna Methylation ◽  
Systolic Blood Pressure ◽  
Pulse Pressure ◽  
Chronological Age ◽  
Cross Sectional ◽  
High Systolic Blood Pressure ◽  
Aging Rate ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration

Background Individuals of the same chronological age may exhibit diverse susceptibilities to death. However, few studies have investigated the associations between blood pressure and the accelerated aging. Methods and Results A cross‐sectional study was conducted in 288 adults aged ≥50 years. We assessed the DNA methylation‐based measures of biological age using CpG sites on the Illumina HumanMethylationEPIC BeadChip. Epigenetic age acceleration metrics were derived by regressing residuals (ΔAge) and ratios (aging rate) of DNA methylation age on chronological age. Dose‐response relationships between blood pressure and epigenetic age acceleration were quantified using multiple linear regression and restricted cubic regression models. We found that each 10–mm Hg increase in systolic blood pressure was associated with 0.608 (95% CI, 0.231–0.984) years increase in ΔAge and 0.007 (95% CI, 0.002–0.012) increase in aging rate; meanwhile, for pulse pressure, the increase was 1.12 (95% CI, 0.625–1.61) years for ΔAge and 0.013 (95% CI, 0.007–0.020) for aging rate. Subgroup analysis showed that the significant associations of systolic blood pressure and pulse pressure with epigenetic age acceleration appeared to be limited to women, although interactions between blood pressure and sex were not significant ( P values for interaction >0.05). The combination of women and hypertension was associated with a much higher increase in ΔAge (β [95% CI], 4.05 [1.07–7.02]) and aging rate (β [95% CI], 0.047 [0.008–0.087]), compared with male participants without hypertension. Conclusions Our findings suggested that high systolic blood pressure and pulse pressure were associated with the epigenetic age acceleration, providing important clues for relationships between blood pressure and epigenetic aging.

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

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.

FRAILTY IS NOT ASSOCIATED WITH MISTREATMENT

2017 ◽  
pp. 1-4
Author(s):  
S.D. Piña-Escudero ◽  
J.M.A. García-Lara ◽  
J.A. Avila-Funes
Keyword(s):  
Cross Sectional Study ◽  
Social Consequences ◽  
Community Dwelling ◽  
Frailty Phenotype ◽  
Cross Sectional ◽  
Logistic Regression Models ◽  
Health Related ◽  
The Mean ◽  
Unadjusted Analysis ◽  
Frailty Score

Muscle Frailty has been previously associated with increased vulnerability for adverse health-related outcomes that could lead to social consequences such as mistreatment. The aim of this cross-sectional study is to determine the association between frailty and mistreatment in 852 community-dwelling persons aged 70 or older. Mistreatment was defined as one positive answer in the Geriatric Mistreatment Scale and frailty was used as a continuum where the greater number of positive criteria according to Fried et al. indicates a higher frailty score. Multivariate logistic regression models were run to establish this association. The mean age of participants was 77.7 years (SD=6.1). Prevalence of frailty phenotype and mistreatment were 13.9% and 20% respectively. Unadjusted analysis showed frailty score was associated with mistreatment (OR = 1.16; 95% CI 1.02 to 1.3, p=0.022). However, after adjustment, the association was no longer present. The results showed that in the presence of other geriatric syndromes such as disability or depression, frailty did not show association with mistreatment in this population.

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

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.

scholarly journals The Relationship between Body Mass Index, Obesity, and LINE-1 Methylation: A Cross-Sectional Study on Women from Southern Italy

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Giuliana Favara ◽  
Claudia La Mastra ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Smoking Status ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
The Relationship

Uncovering the relationship between body mass index (BMI) and DNA methylation could be useful to understand molecular mechanisms underpinning the effects of obesity. Here, we presented a cross-sectional study, aiming to evaluate the association of BMI and obesity with long interspersed nuclear elements (LINE-1) methylation, among 488 women from Catania, Italy. LINE-1 methylation was assessed in leukocyte DNA by pyrosequencing. We found a negative association between BMI and LINE-1 methylation level in both the unadjusted and adjusted linear regression models. Accordingly, obese women exhibited lower LINE-1 methylation level than their normal weight counterpart. This association was confirmed after adjusting for the effect of age, educational level, employment status, marital status, parity, menopause, and smoking status. Our findings were in line with previous evidence and encouraged further research to investigate the potential role of DNA methylation markers in the management of obesity.

Per- and polyfluoroalkyl substances, epigenetic age and DNA methylation: a cross-sectional study of firefighters

Epigenomics ◽  
2021 ◽  
Author(s):  
Jaclyn M Goodrich ◽  
Miriam M Calkins ◽  
Alberto J Caban-Martinez ◽  
Todd Stueckle ◽  
Casey Grant ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cross Sectional Study ◽  
Serum Concentrations ◽  
Sectional Study ◽  
Cross Sectional ◽  
Toxicity Biomarkers ◽  
Epigenetic Age ◽  
Polyfluoroalkyl Substances ◽  
Blood Leukocyte ◽  
Epic Array

Background: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. Methods: With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Results: Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. Conclusion: PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

scholarly journals Epigenetic Clocks and Allostatic Load Reveal Potential Sex-Specific Drivers of Biological Aging

2019 ◽  
Author(s):  
Cathal McCrory ◽  
Giovanni Fiorito ◽  
Sinead McLoughlin ◽  
Silvia Polidoro ◽  
Cliona Ni Cheallaigh ◽  
...  
Keyword(s):  
Allostatic Load ◽  
Accelerated Aging ◽  
Community Dwelling ◽  
Biological Aging ◽  
Cross Sectional ◽  
Metabolic Dysregulation ◽  
Age Related ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
Dna Methylation Age

Abstract Allostatic load (AL) and epigenetic clocks both attempt to characterize the accelerated aging of biological systems, but at present it is unclear whether these measures are complementary or distinct. This study examines the cross-sectional association of AL with epigenetic age acceleration (EAA) in a subsample of 490 community-dwelling older adults participating in The Irish Longitudinal study on Aging (TILDA). A battery of 14 biomarkers representing the activity of four different physiological systems: immunological, cardiovascular, metabolic, renal, was used to construct the AL score. DNA methylation age was computed according to the algorithms described by Horvath, Hannum, and Levine allowing for estimation of whether an individual is experiencing accelerated or decelerated aging. Horvath, Hannum, and Levine EAA correlated 0.05, 0.03, and 0.21 with AL, respectively. Disaggregation by sex revealed that AL was more strongly associated with EAA in men compared with women as assessed using Horvath’s clock. Metabolic dysregulation was a strong driver of EAA in men as assessed using Horvath and Levine’s clock, while metabolic and cardiovascular dysregulation were associated with EAA in women using Levine’s clock. Results indicate that AL and the epigenetic clocks are measuring different age-related variance and implicate sex-specific drivers of biological aging.

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

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.

Sign in / Sign up

Export Citation Format

Share Document