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 Do epigenetic clocks provide explanations for sex differences in lifespan? A cross-sectional twin study

2021 ◽  
Author(s):  
Anna Kankaanpää ◽  
Asko Tolvanen ◽  
Pirkko Saikkonen ◽  
Aino Heikkinen ◽  
Eija K. Laakkonen ◽  
...  
Keyword(s):  
Sex Differences ◽  
Life Expectancy ◽  
Biological Aging ◽  
Related Factors ◽  
Cross Sectional ◽  
Mediating Role ◽  
Epigenetic Age ◽  
Path Modelling ◽  
Epigenetic Age Acceleration ◽  
The Difference

ABSTRACTBackgroundThe sex gap in life expectancy has been narrowing in Finland over the past four to five decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging that predict lifespan. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults.MethodsOur sample included same-sex younger and older twins (21-42-y, n = 1110; 50-76-y, n = 763) and younger opposite-sex twins (21-30-y, n = 302). Blood-based DNA methylation (DNAm) was used to compute epigenetic age acceleration by four epigenetic clocks as a measure of biological aging. Path modelling was used to study whether the association between sex and biological aging is mediated through lifestyle-related factors, i.e. education, body mass index, smoking, alcohol use, and physical activity.FindingsIn comparison to women, men were biologically older and, in general, they had unhealthier life habits. The effect of sex on biological aging was partly mediated by smoking, but only in older twins. Sex was directly associated with biological aging and the association was stronger in older twins.InterpretationPreviously reported sex differences in lifespan are also evident in biological aging. Declining smoking prevalence among men is a plausible explanation for the narrowing of the difference in life expectancy between the sexes. Data generated by the epigenetic clocks may help in estimating the effects of lifestyle and environmental factors on aging and in predicting aging in future generations.

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 Childhood intelligence attenuates the association between biological ageing and health outcomes in later

2019 ◽  
Author(s):  
Anna J. Stevenson ◽  
Daniel L. McCartney ◽  
Robert F. Hillary ◽  
Paul Redmond ◽  
Adele M. Taylor ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Cognitive Ability ◽  
Later Life ◽  
Chronological Age ◽  
Cross Sectional ◽  
Biological Ageing ◽  
Age Related ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
Early Life Factors

AbstractThe identification of biomarkers that discriminate individual ageing trajectories is a principal target in ageing research. Some of the most promising predictors of biological ageing have been developed using DNA methylation. One recent candidate, which tracks age-related phenotypes in addition to chronological age, is ‘DNAm PhenoAge’. Here, we performed a phenome-wide association analysis of this biomarker in a cohort of older adults to assess its relationship with a comprehensive set of both historical and contemporaneously-measured phenotypes. Higher than expected DNAm PhenoAge compared to chronological age, known as epigenetic age acceleration, was found to associate with a number of blood, cognitive, physical fitness and lifestyle variables, and with mortality. Notably, DNAm PhenoAge, assessed at age 70, was associated with cognitive ability at age 11, and with educational attainment. Adjusting for age 11 cognitive ability attenuated the majority of the cross-sectional later-life associations between DNAm PhenoAge and health outcomes. These results highlight the importance of early-life factors on healthy ageing.

scholarly journals Childhood intelligence attenuates the association between biological ageing and health outcomes in later life

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna J. Stevenson ◽  
Daniel L. McCartney ◽  
Robert F. Hillary ◽  
Paul Redmond ◽  
Adele M. Taylor ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Cognitive Ability ◽  
Later Life ◽  
Chronological Age ◽  
Cross Sectional ◽  
Biological Ageing ◽  
Age Related ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
Early Life Factors

AbstractThe identification of biomarkers that discriminate individual ageing trajectories is a principal target of ageing research. Some of the most promising predictors of biological ageing have been developed using DNA methylation. One recent candidate, which tracks age-related phenotypes in addition to chronological age, is ‘DNAm PhenoAge’. Here, we performed a phenome-wide association analysis of this biomarker in a cohort of older adults to assess its relationship with a comprehensive set of both historical, and contemporaneously-measured, phenotypes. Higher than expected DNAm PhenoAge compared with chronological age, known as epigenetic age acceleration, was found to associate with a number of blood, cognitive, physical fitness and lifestyle variables, and with mortality. Notably, DNAm PhenoAge, assessed at age 70, was associated with cognitive ability at age 11, and with educational attainment. Adjusting for age 11 cognitive ability attenuated the majority of the cross-sectional later-life associations between DNAm PhenoAge and health outcomes. These results highlight the importance of early life factors on healthy older ageing.

scholarly journals BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for BMI

2021 ◽  
Author(s):  
Sara Lundgren ◽  
Sara Kuitunen ◽  
Kirsi H. Pietiläinen ◽  
Mikko Hurme ◽  
Mika Kähönen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Meta Analysis ◽  
Accelerated Aging ◽  
Positive Association ◽  
Shared Environment ◽  
Epigenetic Clock ◽  
450K Array ◽  
Cross Sectional ◽  
Age Related ◽  
Epigenetic Age

ABSTRACTBackgroundObesity is a heritable complex phenotype which can increase the risk of age-related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various “epigenetic clocks.” Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely relates with mortality.ObjectivesWe aimed to assess the cross-sectional association of BMI with age acceleration in twins to limit confounding by genetics and shared environment.Methods and ResultsParticipants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twins, and DNAm was measured using the Illumina 450k array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p-value = 6.1 × 10−12) per 1-unit BMI increase. Additionally, heavier twins in a BMI-discordant MZ twin pair (ΔBMI > 3 kg/m2) had an epigenetic age 5.2 months older than their lighter co-twin (p-value = 0.0074). We also found a positive association between log(HOMA-IR) and age acceleration, confirmed by a meta-analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p-value = 0.0025) from adjusted models.ConclusionWe identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance.

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.

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.

scholarly journals Factors associated with physical, psychological and social frailty among community-dwelling older persons in Europe: a cross-sectional study of Urban Health Centres Europe (UHCE)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lizhen Ye ◽  
Liset E. M. Elstgeest ◽  
Xuxi Zhang ◽  
Tamara Alhambra-Borrás ◽  
Siok Swan Tan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Urban Health ◽  
Cross Sectional Study ◽  
Community Dwelling ◽  
Household Composition ◽  
European Countries ◽  
Sectional Study ◽  
Related Condition ◽  
Cross Sectional ◽  
Age Related

Abstract Background Frailty is an age-related condition resulting in a state of increased vulnerability regarding functioning across multiple systems. It is a multidimensional concept referring to physical, psychological and social domains. The purpose of this study is to identify factors (demographic characteristics, lifestyle factors and health indicators) associated with overall frailty and physical, psychological and social frailty in community-dwelling older people from five European countries. Methods This cross-sectional study used baseline data from 2289 participants of the Urban Health Center European project in five European countries. Multivariable logistic regression models were used to assess associations of the factors with overall frailty and the three frailty domains. Results The mean age was 79.7 (SD = 5.7). Participants who were older, were female, had secondary or equivalent education, lived alone, not at risk of alcohol use, were less physically active, had multi-morbidity, were malnourished or with a higher level of medication risk, had higher odds of overall frailty (all P < 0.05). Age was not associated with psychological and social frailty; sex was not associated with social frailty; smoking and migration background was not associated with overall frailty or any of its domains. There existed an interaction effect between sex and household composition regarding social frailty (P < 0.0003). Conclusions The present study contributed new insights into the risk factors for frailty and its three domains (physical, psychological and social frailty). Nurses, physicians, public health professionals and policymakers should be aware of the risk factors of each type of frailty. Furthermore, examine these risk factors more comprehensively and consider overall frailty as well as its three domains in order to further contribute to decision-making more precisely on the prevention and management of frailty. Trial registration The intervention of the UHCE project was registered in the ISRCTN registry as ISRCTN52788952. The date of registration is 13/03/2017.

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 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.

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