Epigenetic Age Acceleration in Adolescence Associates With BMI, Inflammation, and Risk Score for Middle Age Cardiovascular Disease

Abstract

Background ‘Accelerated ageing’, assessed by adult DNA methylation predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age 17-years) associated with adiposity/CVD-risk measured (ages 17, 20, 22-years), and projected CVD by middle-age. Methods DNA methylation measured in peripheral blood provided 2 estimates of epigenetic age acceleration; intrinsic (IEAA, (preserved across cell types) and extrinsic (EEAA, dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound and DEXA (ages 17, 20, 22 years). CVD-risk factors (lipids, HOMA-IR, blood pressure, inflammatory markers) were assessed at age 17-years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients/5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD-risk factors and CVD development. Results In 995 participants (49.6% female, age 17.3+/-0.6 years), EEAA (/5-years) was associated with increased BMI of 2.4% (95%CI 1.2-3.6%) and 2.4% (0.8-3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3-33%) in hsCRP, 10% (4-17%) in interferon-gamma induced protein (IP-10) and 4% (2-6%) in tumour necrosis factor receptor 2 (sTNFR2), adjusted for BMI and HOMA-IR. EEAA(/5-years) results in a 4% increase in hard endpoints of CVD by 47 years old and a 3% increase, after adjustment for conventional risk factors. Conclusions Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle-age CVD. Irrespective whether this is cause or effect, assessing epigenetic age might refine disease prediction.

Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans

“…In our study, IEAA was associated with SBP, and both EEAA and GrimAA were associated with pulse pressure. Previous studies on the association between IEAA and EEAA and cardiometabolic measures show inconsistent findings [ 13 , 20 , 32 , 33 ]. A previous study of IEAA and EEAA in the Women’s Health initiative (WHI) found no associations with systolic or diastolic blood pressure after adjusting for diet and metabolic syndrome symptoms [ 32 ].…”

Psychosocial stress and epigenetic aging

“…Furthermore, alternative measures of biological aging, such as neuroimaging-derived brain age, have revealed the positive association between prenatal undernutrition and premature brain aging (Franke, Gaser, Roseboom, Schwab, & de Rooij, 2018). These results highlight the interest of exploring simultaneously different markers of biological age, as different organs are known to have independent age rates in the same individuals; thus, there could be tissue-specific effects of epigenetic age predictors, e.g., brain epigenetic aging better informs about neurodegenerative processes (Levine et al, 2015) while blood epigenetic age better reflects cardiovascular risk (Huang et al, 2019).…”

Telomere length and epigenetic age acceleration in adolescents with anxiety disorders

“…Some studies investigated the association between DNAm age with posttraumatic stress disorder 29 , 30 , schizophrenia 31 , 32 , depression 33 , generalized anxiety disorder 29 and bipolar disorder 26 , and also found inconsistent findings. In adolescence, AA was associated with inflammation, the probability of middle age cardiovascular disease 34 , as well as higher odds for internalizing and thought problems 35 .…”