Are sex differences in cognitive impairment reflected in epigenetic age acceleration metrics?

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.

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Association of blood‐based epigenetic age acceleration with cognitive impairment and brain outcomes by cardiovascular disease among women

Alzheimer s & Dementia ◽

10.1002/alz.051774 ◽

2021 ◽

Vol 17 (S5) ◽

Author(s):

Aladdin H. Shadyab ◽

Linda K. McEvoy ◽

Steve Horvath ◽

Eric A. Whitsel ◽

Stephen R. Rapp ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cognitive Impairment ◽

Epigenetic Age ◽

Epigenetic Age Acceleration

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Association of Epigenetic Age Acceleration with Incident Mild Cognitive Impairment and Dementia Among Older Women

The Journals of Gerontology Series A ◽

10.1093/gerona/glab245 ◽

2021 ◽

Author(s):

Aladdin H Shadyab ◽

Linda K McEvoy ◽

Steve Horvath ◽

Eric A Whitsel ◽

Stephen R Rapp ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Older Women ◽

Biological Aging ◽

Prospective Analysis ◽

Health Initiative ◽

Epigenetic Age ◽

Epigenetic Age Acceleration ◽

Stratified Analysis

Abstract Background Epigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of four AgeAccel measures with incident MCI and dementia. Methods This prospective analysis included 578 older women from the Women’s Health Initiative Memory Study selected for a case-cohort study of coronary heart disease (CHD). Women were free of CHD and cognitive impairment at baseline. Associations of AgeAccel measures (intrinsic AgeAccel [IEAA], extrinsic AgeAccel [EEAA], AgeAccelPheno, and AgeAccelGrim) with risks for incident adjudicated diagnoses of MCI and dementia overall and stratified by incident CHD status were evaluated. Results IEAA was not significantly associated with MCI (HR 1.23; 95% CI 0.99-1.53), dementia (HR 1.10; 95% CI 0.88-1.38), or cognitive impairment (HR 1.18; 95% CI 0.99-1.40). In stratified analysis by incident CHD status, there was a 39% (HR 1.39; 95% CI 1.07-1.81) significantly higher risk of MCI for every 5-year increase in IEAA among women who developed CHD during follow-up. Other AgeAccel measures were not significantly associated with MCI or dementia. Conclusion IEAA was not significantly associated with cognitive impairment overall but was associated with impairment among women who developed CHD. Larger studies designed to examine associations of AgeAccel with cognitive impairment are needed, including exploration of whether associations are stronger in the setting of underlying vascular pathologies.

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Structural MR correlates of epigenetic age acceleration

Pharmacopsychiatry ◽

10.1055/s-0035-1558033 ◽

2015 ◽

Vol 48 (06) ◽

Author(s):

P Sämann ◽

A Zannas ◽

T Carrillo ◽

E Binder

Keyword(s):

Epigenetic Age ◽

Epigenetic Age Acceleration

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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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The early-life exposome and epigenetic age acceleration in children

Environment International ◽

10.1016/j.envint.2021.106683 ◽

2021 ◽

Vol 155 ◽

pp. 106683

Author(s):

Paula de Prado-Bert ◽

Carlos Ruiz-Arenas ◽

Marta Vives-Usano ◽

Sandra Andrusaityte ◽

Solène Cadiou ◽

...

Keyword(s):

Early Life ◽

Epigenetic Age ◽

Epigenetic Age Acceleration

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Maternal Dietary Fatty Acid Composition and Newborn Epigenetic Aging—A Geometric Framework Approach

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqab318 ◽

2021 ◽

Author(s):

Nicholas A Koemel ◽

Alistair M Senior ◽

Hasthi U Dissanayake ◽

Jason Ross ◽

Rowena L McMullan ◽

...

Keyword(s):

Newborn Infants ◽

Intima Media Thickness ◽

Response Surfaces ◽

Geometric Framework ◽

Body Fatness ◽

Epigenetic Aging ◽

Epigenetic Age ◽

Framework Approach ◽

Epigenetic Age Acceleration ◽

Aortic Intima

Abstract Background Maternal nutrition is associated with epigenetic and cardiometabolic risk factors in offspring. Research in humans has primarily focused on assessing the impact of individual nutrients. Objective We sought to assess the collective impact of maternal dietary monounsaturated (MUFA), polyunsaturated (PUFA), and saturated fat (SFA) on epigenetic aging and cardiometabolic risk markers in healthy newborn infants using a geometric framework approach. Design Body fatness (n = 162), aortic intima-media thickness (n = 131), heart rate variability (n = 118), and epigenetic age acceleration (n = 124) were assessed in newborn infants. Maternal dietary intake was cross-sectionally assessed in the immediate postpartum period via a validated 80-item self-administered food-frequency questionnaire. Generalized additive models were used to explore interactive associations of nutrient intake, with results visualized as response surfaces. Results After adjustment for total energy intake, maternal age, gestational age, and sex there was a 3-way interactive association of MUFA, PUFA, and SFA (P = 0.001) with newborn epigenetic aging. This suggests that the nature of each fat class association depends upon one another. Response surfaces revealed MUFA was positively associated with newborn epigenetic age acceleration only at proportionately lower intakes of SFA or PUFA. We also demonstrate a potential beneficial association of omega-3 PUFA with newborn epigenetic age acceleration (P = 0.008). There was no significant association of fat class with newborn aortic intima-media thickness, heart rate variability, or body fatness. Conclusions In this study, we demonstrate an association between maternal dietary fat class composition and epigenetic aging in newborns. Future research should consider other characteristics such as the source of maternal dietary fatty acids.

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