Department of Epidemiology, School of Public Health, Brown University, 121 South Main Street, Providence, RI, 02903, USA.
Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA.
Clin Epigenetics. 2024 Nov 19;16(1):163. doi: 10.1186/s13148-024-01779-8.
Cardiometabolic risk factors among youth are rising. Epigenetic age acceleration, a biomarker for aging and disease-risk, has been associated with adiposity in children, but its association with other cardiometabolic risk markers remains understudied. We employed data from the Health Outcomes and Measures of the Environment (HOME) study, a prospective pregnancy and birth cohort in the greater Cincinnati metropolitan area, to examine whether accelerated epigenetic age at birth as well as accelerated epigenetic age and faster pace of biological aging at age 12 years were associated with higher cardiometabolic risk in adolescents.
After adjusting for potential confounders, including estimated cell type proportions, epigenetic gestational age acceleration at birth, derived from the Bohlin, Knight, and Haftorn clocks using cord blood DNA methylation data, was not associated with cardiometabolic risk z-scores or individual cardiometabolic risk score components (visceral fat, leptin to adiponectin ratio, HOMA-IR, triglycerides to HDL-C ratio, HbA1c, or systolic blood pressure) at age 12 years. We also did not observe any associations of epigenetic age acceleration, calculated with Horvath's skin and blood, Hannum's, and Wu's epigenetic clocks using peripheral blood at age 12 years, with these same cardiometabolic risk markers. In contrast, faster pace of biological aging was associated with higher cardiometabolic risk [βs (95% CIs)] cardiometabolic risk score 0.25 (0.07, 0.42); visceral fat 0.21 (0.05, 0.38); and hemoglobin A1c 0.23 (0.05, 0.41) per standard deviation increase in pace of biological aging. Faster pace of biological aging was also positively associated with systolic blood pressure, triglycerides to HDL-C ratio, HOMA-IR, and leptin to adiponectin ratio, although these associations were not statistically significant.
Our findings provide evidence that faster pace of biological aging was associated with higher cardiometabolic risk score, visceral fat, and HbA1c at age 12 years. Further research is needed to determine whether these associations persist from adolescence through adulthood.
年轻人的心血管代谢危险因素正在上升。表观遗传年龄加速是衰老和疾病风险的生物标志物，已与儿童肥胖有关，但它与其他心血管代谢风险标志物的关系仍有待研究。我们利用辛辛那提大都市区更大范围内的前瞻性妊娠和出生队列健康结果和环境测量（HOME）研究的数据，研究了出生时加速的表观遗传年龄以及 12 岁时加速的表观遗传年龄和更快的生物学衰老速度是否与青少年的更高心血管代谢风险相关。
在调整了潜在的混杂因素（包括估计的细胞类型比例）后，使用脐带血 DNA 甲基化数据从 Bohlin、Knight 和 Haftorn 时钟得出的出生时的表观遗传孕龄加速与 12 岁时的心血管代谢风险 z 评分或个别心血管代谢风险评分成分（内脏脂肪、瘦素与脂联素比值、HOMA-IR、甘油三酯与高密度脂蛋白胆固醇比值、HbA1c 或收缩压）无关。我们也没有观察到使用 12 岁时外周血的 Horvath 皮肤和血液、Hannum 和 Wu 表观遗传时钟计算的表观遗传年龄加速与这些相同的心血管代谢风险标志物有任何关联。相比之下，更快的生物学衰老速度与更高的心血管代谢风险相关[βs（95%置信区间）]心血管代谢风险评分 0.25（0.07，0.42）；内脏脂肪 0.21（0.05，0.38）；血红蛋白 A1c 0.23（0.05，0.41）每标准偏差增加生物老化速度。更快的生物学衰老速度与收缩压、甘油三酯与高密度脂蛋白胆固醇比值、HOMA-IR 和瘦素与脂联素比值呈正相关，尽管这些关联没有统计学意义。
我们的研究结果提供了证据表明，更快的生物学衰老速度与 12 岁时更高的心血管代谢风险评分、内脏脂肪和 HbA1c 相关。需要进一步的研究来确定这些关联是否从青少年持续到成年。
