Childhood Growth, Biological Aging and Midlife Cardio-Metabolic Outcomes

中年是心脏代谢疾病的关键时期，包括冠状动脉疾病， 高血压和2型糖尿病。儿童不良生长影响的重要性 在成人心脏代谢性疾病方面的经验早已得到认可。端粒长度和端粒 DNA甲基化(DNaM)年龄与年龄高度相关，被认为是 人类衰老的生物标志物。最近的研究表明，端粒长度和端粒长度的变化 DNaM可预测心脏代谢性疾病、动脉粥样硬化和死亡率。尽管进行了广泛的研究 关于心脏代谢性疾病和生物衰老的早期起源， 产前经历、早期生命发育模式和心脏代谢衰老过程不是 很好地理解了这一点，并且仍然是一个重要的研究领域。这个二次数据分析建议是 针对以下具体目标：1)考察早期生命成长轨迹的影响 中年黑人和老年人端粒年龄、dNaM年龄与心脏代谢性疾病的关系 2)探讨BMI-端粒和BMI-dNaM与BMI-dNaM的时间关系。 它们的时间序列模式对成人心脏代谢疾病的影响；3)确定 端粒和dNaM老化生物标记物在生命早期生长相关中的中介作用 和成人心脏代谢风险的风险负担；4)检查种族、性别和出生 权重修改关联和调解效果参数。心脏代谢的结果 包括高血压、2型糖尿病、冠心病和亚临床心血管疾病 措施。端粒长度和dNaM年龄将作为调节因子。具体目标将是 通过利用博加卢萨心脏研究的现有纵向队列实现了以下目标 从1973年开始的童年生活。我们建议分析两个队列：3627个纵向队列 成年人(2,285名白人和1,342名黑人)，年龄28-61岁，身高、体重指数 (BMI)，皮肤皱纹在童年测量3-9次，成年测量2-6次，以及亚队列 1168名成年人(747名白人和421名黑人)也有端粒数据和全基因组450K 成年期在相隔5-12年的两个时间点测量dNaM分布。交叉滞后模型 用于时间关系分析、中介分析模型、回归模型和交互 将进行分析模型。早期生命发育对心脏代谢影响的研究结果 与生物衰老标记物有关的疾病将有助于识别高危个人和 早期生活中选择新的治疗和干预策略。

Middle age is a critical period for cardio-metabolic diseases, including coronary artery disease, hypertension and type 2 diabetes. The importance of impact of childhood adverse growth experience on adult cardio-metabolic diseases has long been recognized. Telomere length and DNA methylation (DNAm) age are highly correlated with chronological age and considered as biomarkers of human aging. Recent studies have clarified that changes in telomere length and DNAm predict cardio-metabolic disease, atherosclerosis and mortality. Despite extensive studies on the early origins of cardio-metabolic disease and biological aging, the combined effect of prenatal experience, early life developmental patterns and cardio-metabolic aging process is not well understood and remains an important research area. This secondary data analysis proposal is directed to the following Specific Aims: 1) To examine the impact of early life growth trajectory patterns on telomere age, DNAm age and cardio-metabolic disease in middle-aged black and white adults; 2) To investigate the temporal relationship of BMI-telomere and BMI-DNAm and the effect of their temporal sequence patterns on adult cardio-metabolic disease; 3) To determine the mediation effect of telomere and DNAm aging biomarkers on the association of early life growth and risk burden with adult cardio-metabolic risk; 4) To examine whether race, gender and birth weight modify the association and mediation effect parameters. The cardio-metabolic outcomes include hypertension, type 2 diabetes, coronary artery disease and subclinical cardiovascular measures. Telomere length and DNAm age will be used as mediators. The specific aims will be achieved by leveraging the existing longitudinal cohort of the Bogalusa Heart Study followed from childhood since 1973. We propose to analyze two cohorts: a longitudinal cohort of 3,627 adults (2,285 whites and 1,342 blacks), aged 28-61 years, who have height, body mass index (BMI), skin folds measured 3-9 times in childhood and 2-6 times in adulthood, and a sub-cohort of 1,168 adults (747 whites and 421 blacks) who also have telomere data and genome-wide 450K DNAm profiles measured at two time-points 5-12 years apart in adulthood. Cross-lagged models for temporal relationship analysis, mediation analysis models, regression models and interaction analysis models will be performed. Findings on the impact of early life growth on cardio-metabolic disease in relation to biological aging markers will facilitate identification of high risk individuals and selection of novel therapeutic and intervention strategies in early life.