权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Biological Embedding of Early-Life SES

生命早期 SES 的生物嵌入

基本信息

批准号：
8425987
负责人：
Gregory Evan Miller
金额：
$ 30.08万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-12-01 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8425987
关键词：
Accounting Address Adolescence Adult Affect Age American Anti-Inflammatory Agents Anti-inflammatory Area Behavior Behavior Therapy Behavioral Sciences Biochemical Biological Biological Markers Brain hemorrhage C-reactive protein Cardiovascular Diseases Child Childhood Chromosomes Cognition Communicable Diseases Communities Conflict (Psychology)Coronary heart disease DNA DNA Packaging DNA Sequence Depressed mood Development Disadvantaged Disease Economics Emotional Emotions Enrollment Environment Epigenetic Process Exhibits Exposure to Family Fathers Genes Genetic Transcription Genome Genomics Health Heart Diseases Histones Immune response Immune system Individual Inflammation Inflammatory Inflammatory Response Pathway Interleukin-6 Intervention L Cells Learning Life Life Style Light Link Longevity Lung diseases Medical Methods Modeling Modification Molecular Genetics Mothers Myocardial Infarction Nucleotides Outcome Pathway interactions Persons Phenotype Policies Poverty Preventive Process Proteins Proxy Repression Research Research Project Grants Risk Sampling Signal Transduction Socioeconomic Status Staging System TimeLine Variant Vascular Diseases Work Youth base behavioral/social science biobehavior critical period design early childhood experience health disparity information gathering insight low socioeconomic status middle age physical conditioning pollutant programs psychosocial response social social science research socioeconomics vigilance volunteer

项目摘要

DESCRIPTION (provided by applicant): Socioeconomic status (SES) during early life is an important determinant of vulnerability to cardiovascular disease in adulthood. Because these effects are not simply a result of the more direct influences of social standing in adulthood, they raise challenging mechanistic questions about how early-life SES gets biologically embedded for the long-term. This proposal advances an epigenetic programming hypothesis to explain this process. It posits that psychosocial experiences associated with low early-life SES are programmed in the genome via epigenetic mechanisms, or acquired changes in genomic activity that are not due to changes in DNA sequence. In a study of 420 volunteers, we will evaluate the hypothesis that individuals who spent their early years in low-SES environments were exposed to greater familial turmoil and have developed vigilant, pessimistic outlooks on life. We further expect these experiences to have become embedded in the immune system through epigenetic modifications, and to manifest as a pro-inflammatory phenotype beginning in adolescence and persisting through adulthood. This phenotype will be characterized by activation of pro-inflammatory transcription control pathways and increased concentrations of the inflammatory biomarkers C-reactive protein and interleukin-6. This work will shed light on the biobehavioral mechanisms underlying SES disparities, with implications for preventative interventions.

描述（由申请人提供）：生命早期的社会经济地位（SES）是成年后易患心血管疾病的重要决定因素。因为这些影响不仅仅是成年后社会地位的直接影响的结果，它们提出了具有挑战性的机制问题，即早期社会经济地位如何在生物学上长期嵌入。这一建议提出了一个表观遗传编程假说来解释这一过程。它假定与低早期社会经济地位相关的心理社会经历是通过表观遗传机制在基因组中编程的，或者是由于DNA序列的变化而不是由于基因组活动的获得性变化。在一项对420名志愿者的研究中，我们将评估一个假设，即早年在低社会经济地位环境中度过的个体暴露于更大的家庭动荡，并形成了警惕，悲观的生活观。我们进一步期望这些经历通过表观遗传修饰嵌入免疫系统，并表现为从青春期开始并持续到成年的促炎表型。该表型的特征在于促炎转录控制途径的激活和炎性生物标志物C-反应蛋白和白细胞介素-6的浓度增加。这项工作将揭示SES差异背后的生物行为机制，并对预防性干预措施产生影响。