Epigenetic age acceleration in adolescence associates with BMI, inflammation and risk score for middle age cardiovascular disease

R C Huang, K A Lillycrop, L J Beilin, K M Godfrey, D Anderson, T A Mori, S Rauschert, J M Craig, W H Oddy, O T Ayonrinde, C E Pennell, J D Holbrook, P E Melton

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3012-3024
Number of pages13
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number7
Early online date20 Feb 2019
DOIs
Publication statusPublished - Jul 2019

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Epigenomics
Cardiovascular Diseases
Inflammation
Adiposity
DNA Methylation
Receptors, Tumor Necrosis Factor, Type II
Aging of materials
Anthropometry
Methylation
Blood pressure
Interferon-gamma
Blood
Ultrasonics
Blood Pressure
Lipids

Cite this

@article{f3ba96a765034527ba3727911a274982,
title = "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.",
author = "Huang, {R C} and Lillycrop, {K A} and Beilin, {L J} and Godfrey, {K M} and D Anderson and Mori, {T A} and S Rauschert and Craig, {J M} and Oddy, {W H} and Ayonrinde, {O T} and Pennell, {C E} and Holbrook, {J D} and Melton, {P E}",
year = "2019",
month = "7",
doi = "10.1210/jc.2018-02076",
language = "English",
volume = "104",
pages = "3012--3024",
journal = "Journal of Endocrinology & Metabolism",
issn = "0021-972X",
publisher = "ENDOCRINE SOC",
number = "7",

}

Epigenetic age acceleration in adolescence associates with BMI, inflammation and risk score for middle age cardiovascular disease. / Huang, R C; Lillycrop, K A; Beilin, L J; Godfrey, K M; Anderson, D; Mori, T A; Rauschert, S; Craig, J M; Oddy, W H; Ayonrinde, O T; Pennell, C E; Holbrook, J D; Melton, P E.

In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 7, 07.2019, p. 3012-3024.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Epigenetic age acceleration in adolescence associates with BMI, inflammation and risk score for middle age cardiovascular disease

AU - Huang, R C

AU - Lillycrop, K A

AU - Beilin, L J

AU - Godfrey, K M

AU - Anderson, D

AU - Mori, T A

AU - Rauschert, S

AU - Craig, J M

AU - Oddy, W H

AU - Ayonrinde, O T

AU - Pennell, C E

AU - Holbrook, J D

AU - Melton, P E

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

U2 - 10.1210/jc.2018-02076

DO - 10.1210/jc.2018-02076

M3 - Article

VL - 104

SP - 3012

EP - 3024

JO - Journal of Endocrinology & Metabolism

JF - Journal of Endocrinology & Metabolism

SN - 0021-972X

IS - 7

ER -