Childhood Growth, Biological Aging and Midlife Cardio-Metabolic Outcomes

儿童期生长、生物衰老和中年心脏代谢结果

• 批准号: 9750243
• 负责人: WEI CHEN
• 金额: $ 7.57万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750243
• 关键词: Adult; Age; Aging; Area; Atherosclerosis; Back; Biological Aging; Biological Markers; Birth; Birth Certificates; Birth Weight; Body mass index; Cardiovascular system; Child; Childhood; Chronology; Complex; Coronary Arteriosclerosis; DNA Methylation; Data; Data Analyses; Data Set; Development; Disease; Disease Outcome; Elderly; Environmental Risk Factor; Epigenetic Process; Ethnic Origin; Etiology; Fetal Growth; Gender; Gene Expression; Genetic; Grant; Growth; Growth and Development function; Heart; Height; Human; Hypertension; Individual; Intervention; Joints; Left Ventricular Mass; Length; Life; Longitudinal cohort; Measures; Mediating; Mediation; Mediator of activation protein; Metabolic Diseases; Modeling; Modification; Nature; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Pathway interactions; Pattern; Plant Roots; Play; Population; Prevention program; Prevention strategy; Process; Process Measure; Public Health; Race; Research; Research Project Grants; Risk; Risk Factors; Role; Services; Skin; System; Time; Variant; age related; aged; arterial stiffness; cardiometabolic risk; cardiometabolism; carotid intima-media thickness; cohort; course sequence; critical period; experience; genetic variant; genome-wide; healthy aging; high risk; human population study; insight; middle age; mortality; novel therapeutic intervention; prenatal experience; response; secondary analysis; success; telomere; time use; trend

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.

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。童年不良增长影响的重要性 长期以来，人们已经认识到有关成人心脏代谢疾病的经验。端粒长度和 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。最近的研究阐明了端粒长度和 DNAM预测心脏代谢疾病，动脉粥样硬化和死亡率。尽管进行了广泛的研究 关于心脏代谢疾病和生物衰老的早期起源， 产前经验，早期生命发展模式和心脏代谢衰老过程不是 理解，仍然是一个重要的研究领域。该二次数据分析建议是 针对以下特定目的：1）检查早期生命增长轨迹的影响 中年黑色和 白人成年人； 2）研究BMI-Telomere和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衰老生物标志物对早期生命增长的关联的调解作用 成人心甲替代谢风险的风险负担； 4）检查种族，性别和出生是否 重量修改关联和中介效应参数。心脏代谢结果 包括高血压，2型糖尿病，冠状动脉疾病和亚临床心血管 措施。端粒长度和DNAM时代将用作介体。具体目标将是 通过利用Bogalusa心脏研究的现有纵向队列来实现 从1973年开始的童年开始。我们建议分析两个队列：纵向队列3,627 成人（2,285名白人和1,342个黑人），年龄在28-61岁之间，身高，体重指数 （BMI），皮肤折叠在儿童时期3-9倍，成年后2-6次，一组 还有1,168名成年人（747名白人和421个黑人），他们也具有端粒数据和全基因组450K DNAM概况在成年期相隔5 - 12年的两个时间点测量。交叉滞后模型 对于时间关系分析，调解分析模型，回归模型和相互作用 分析模型将进行。关于早期生命增长对心脏代谢的影响的发现 与生物老化标记有关的疾病将有助于识别高风险个体， 在早期的新型治疗和干预策略中的选择。