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

• Published in: The journal of clinical endocrinology and metabolism 2019-07, Vol.104 (7), p.3012-3024
• Main Authors: Huang, Rae-Chi, Lillycrop, Karen A, Beilin, Lawrence J, Godfrey, Keith M, Anderson, Denise, Mori, Trevor A, Rauschert, Sebastian, Craig, Jeffrey M, Oddy, Wendy H, Ayonrinde, Oyekoya T, Pennell, Craig E, Holbrook, Joanna D, Melton, Phillip E
• Format: Article
• Language: English
• Subjects: Absorptiometry, Photon; Adiponectin - metabolism; Adipose tissue; Adolescence; Adolescent; Adolescents; Aging; Aging - genetics; Aging - metabolism; Aging, Premature - genetics; Aging, Premature - metabolism; Algorithms; Anthropometry; Biological response modifiers; Blood Pressure; Body Composition; Body Mass Index; C-reactive protein; C-Reactive Protein - metabolism; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Cardiovascular Diseases - metabolism; Chemokine CXCL10 - metabolism; Child development; Cholesterol, HDL - metabolism; Cholesterol, LDL - metabolism; Clinical s; Deoxyribonucleic acid; DNA; DNA Methylation; Dual energy X-ray absorptiometry; Epigenesis, Genetic - genetics; Epigenetic inheritance; Epigenetics; Female; Humans; Inflammation; Inflammation - genetics; Inflammation - metabolism; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interferon; Interleukin-18 - metabolism; Leptin - metabolism; Lipids; Male; Medical research; Medicine, Experimental; Methylation; Middle age; Middle Aged; Peripheral blood; Receptors, Tumor Necrosis Factor, Type II - metabolism; Risk Assessment; Risk Factors; Tumor necrosis factor; Tumor necrosis factor receptors; Type 2 diabetes; Ultrasound; Western Australia - epidemiology; Young Adult; γ-Interferon
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-02076

Abstract Context “Accelerated aging,” 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) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age. Design DNA methylation measured in peripheral blood provided two 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 dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors [lipids, homeostatic model assessment of insulin resistance (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 per 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 (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ–inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age 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 of whether this is cause or effect, assessing epigenetic age might refine disease prediction. An estimate of biological age determined from peripheral blood DNA from ∼1000 adolescents may refine prediction of cardiovascular risk above and beyond traditional risk factors.