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

Drew R Nannini,Donald M Lloyd-Jones,Jim Ren,Lei Liu,Yinan Zheng,Tao Gao,David R Jacobs,Lifang Hou,Steve Horvath,Tianxiao Huan,Norrina Bai Allen,Philip Greenland,Sadiya S Khan,John T Wilkins,Grace Yoon,Brian T Joyce,Kai Zhang,Jiantao Ma

doi:10.1186/s13148-019-0767-1

Abstract

BackgroundThe 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.ResultsA 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).ConclusionsTo 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.

Highlights

The metabolic syndrome (MetS) is a collection of metabolic disturbances that can lead to various cardiovascular diseases
In conclusion, we identified significant associations between the MetS severity score and both Intrinsic epigenetic age acceleration (IEAA) and EEAA cross-sectionally, suggesting with a greater number of MetS components associated with more advanced epigenetic age acceleration
We identified significant associations between epigenetic age acceleration and incident MetS. These findings provide novel insight into the relationship between epigenetic aging and MetS by indicating metabolic risk factors may accelerate the biological aging process and epigenetic markers of aging may serve as a predictive tool in the development of metabolic disorders

Summary

Introduction

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 metabolic syndrome (MetS) is defined as a collection of metabolic disturbances that includes hypertension, elevated plasma glucose, dyslipidemia, and abdominal obesity [1]. Individuals with MetS are at higher risk for type 2 diabetes, several types of cancer, and cardiovascular morbidity and mortality [2,3,4,5,6]. Previous studies have investigated the association between leukocyte telomere length, a measure of biological age, and the components of MetS. Shorter leukocyte telomere length was found to be associated with higher triglycerides and fasting glucose, lower high-density lipoprotein (HDL)

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