Biological Embedding of Early-Life SES

描述(由申请人提供)：早期生活中的社会经济地位(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更直接影响的结果，它们提出了具有挑战性的机械问题，即早期的SES是如何长期在生物学上嵌入的。这一提议提出了一个表观遗传编程假说来解释这一过程。它假设，与低早期SES相关的心理社会经验是通过表观遗传机制在基因组中编程的，或者是获得的基因组活动的变化，而不是由于DNA序列的变化。在一项对420名志愿者的研究中，我们将评估这一假设，即早年生活在低SES环境中的人暴露在更大的家庭动荡中，并养成了警觉、悲观的人生观。我们还预计，这些经历将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期的促炎表型。这种表型的特征是促炎转录控制通路的激活和炎性生物标记物C-反应蛋白和白介素6浓度的增加。这项工作将阐明SES差异背后的生物行为机制，并对预防性干预产生影响。与公共卫生相关：早年生活在贫困中的人在成年后更有可能罹患心脏病和其他医疗疾病。这项研究试图找出这种现象背后的机制。它考察了这样一种观点，即儿童早期的贫困改变了免疫系统的运作方式，并以一种持续整个寿命的方式发生变化，使一个人在成年后容易患上疾病。

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. PUBLIC HEALTH RELEVANCE: Individuals who spend the early years of their lives in poverty are more likely to develop heart disease and other medical conditions when they reach adulthood. This research project attempts to identify the mechanisms underlying this phenomenon. It examines the idea that poverty in early childhood changes the way the immune system functions, and does so in a fashion that persists across the lifespan and renders a person vulnerable to diseases in adulthood.