Mid‐life epigenetic age, neuroimaging brain age, and cognitive decline: Coronary Artery Risk Development in Young Adults (CARDIA) Study

DNA methylation-based biological age (epigenetic age) has been suggested as a useful biomarker of age-related conditions including type 2 diabetes (T2D), and its newest iterations (GrimAge measurements) have shown early promise. In this study, we explored the association between epigenetic age and incident T2D, in the context of their relationships with obesity. <p>A total of 1,057 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included in the current analyses. We stratified the participants into three groups; normal weight, overweight, and obese. A one-year increase of GrimAge was associated with higher 10-year (Y15 to Y25) incidence of T2D (OR=1.06, 95% CI=1.01-1.11). GrimAge acceleration, which represents the deviation of GrimAge from chronological age, was derived from the residuals of a model of GrimAge and chronological age, and any GrimAge acceleration (Positive GrimAA; having GrimAge older than chronological age) was associated with significantly higher odds of 10-year incidence of T2D in obese participants (OR=2.57, 95% CI=1.61-4.11). Cumulative obesity was estimated by years since obesity onset, and GrimAge partially mediated the statistical association between cumulative obesity and incident diabetes or prediabetes (proportion mediated = 8.0%). </p> In conclusion, both <a>older and accelerated GrimAge were associated with higher risk of T2D, particularly among obese participants. GrimAge also statistically mediated the associations between cumulative obesity and T2D. </a>Our findings suggest that epigenetic age measurements with DNA methylation can potentially be utilized as a risk factor or biomarker associated with T2D development.

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Epigenetic age acceleration and metabolic syndrome in the coronary artery risk development in young adults study

Clinical Epigenetics ◽

10.1186/s13148-019-0767-1 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Drew R. Nannini ◽

Brian T. Joyce ◽

Yinan Zheng ◽

Tao Gao ◽

Lei Liu ◽

...

Keyword(s):

Metabolic Syndrome ◽

Young Adults ◽

Coronary Artery ◽

Severity Score ◽

Biological Aging ◽

Metabolic Disturbances ◽

The Metabolic Syndrome ◽

Epigenetic Biomarkers ◽

Epigenetic Age ◽

Epigenetic Age Acceleration

Abstract Background The metabolic syndrome (MetS) is a collection of metabolic disturbances that can lead to various cardiovascular diseases. Previous studies have shown a more adverse metabolic risk profile is associated with more advanced biological aging. The associations between epigenetic biomarkers of age with MetS, however, are not well understood. We therefore investigated the associations between epigenetic age acceleration and MetS severity score and incident MetS. Results A subset of study participants with available whole blood at examination years 15 and 20 from the Coronary Artery Risk Development in Young Adults Study underwent epigenomic profiling using the Illumina MethylationEPIC Beadchip (~ 850,000 sites). Intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA) were calculated from DNA methylation levels. The MetS severity score was positively associated with IEAA at years 15 (P = 0.016) and 20 (P = 0.016) and EEAA at year 20 (P = 0.040) in cross-sectional analysis. IEAA at year 20 was significantly associated with incident MetS at year 30 (OR = 1.05 [95% CI 1.01, 1.10], P = 0.028). Conclusions To our knowledge, this is the first report of the longitudinal association between epigenetic age acceleration and MetS. These findings suggest that a higher MetS severity score is associated with accelerated epigenetic aging and such aging may play a role in the development of metabolic disorders, potentially serving as a useful biomarker of and early detection tool for future MetS.

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Abstract P175: Association of Midlife Hypertension and a Novel Biomarker of Accelerated Epigenetic Age: Coronary Artery Risk Development in Young Adults (CARDIA) Study

Circulation ◽

10.1161/circ.139.suppl_1.p175 ◽

2019 ◽

Vol 139 (Suppl_1) ◽

Author(s):

Yinan Zheng ◽

Sadiya Khan ◽

Tao Gao ◽

Brian Joyce ◽

Sanjiv Shah ◽

...

Keyword(s):

Young Adults ◽

Coronary Artery ◽

Epigenetic Age

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DNA methylation GrimAge and Incident Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

10.2337/figshare.14336537 ◽

2021 ◽

Author(s):

Kyeezu Kim ◽

Brian T. Joyce ◽

Yinan Zheng ◽

Pamela J. Schreiner ◽

David R. Jacobs Jr. ◽

...

Keyword(s):

Dna Methylation ◽

Young Adults ◽

Coronary Artery ◽

Normal Weight ◽

Incident Diabetes ◽

Chronological Age ◽

Age Related ◽

Epigenetic Age ◽

One Year

DNA methylation-based biological age (epigenetic age) has been suggested as a useful biomarker of age-related conditions including type 2 diabetes (T2D), and its newest iterations (GrimAge measurements) have shown early promise. In this study, we explored the association between epigenetic age and incident T2D, in the context of their relationships with obesity. <p>A total of 1,057 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included in the current analyses. We stratified the participants into three groups; normal weight, overweight, and obese. A one-year increase of GrimAge was associated with higher 10-year (Y15 to Y25) incidence of T2D (OR=1.06, 95% CI=1.01-1.11). GrimAge acceleration, which represents the deviation of GrimAge from chronological age, was derived from the residuals of a model of GrimAge and chronological age, and any GrimAge acceleration (Positive GrimAA; having GrimAge older than chronological age) was associated with significantly higher odds of 10-year incidence of T2D in obese participants (OR=2.57, 95% CI=1.61-4.11). Cumulative obesity was estimated by years since obesity onset, and GrimAge partially mediated the statistical association between cumulative obesity and incident diabetes or prediabetes (proportion mediated = 8.0%). </p> In conclusion, both <a>older and accelerated GrimAge were associated with higher risk of T2D, particularly among obese participants. GrimAge also statistically mediated the associations between cumulative obesity and T2D. </a>Our findings suggest that epigenetic age measurements with DNA methylation can potentially be utilized as a risk factor or biomarker associated with T2D development.

Download Full-text