Biological Embedding of Early-Life SES

项目摘要/摘要 早年的社会经济地位(SES)是易感性的重要决定因素 成年后的心血管疾病。因为这些影响不仅仅是更多的 成年后社会地位的直接影响，他们提出了具有挑战性的机械性问题 关于早期生命的SES是如何在生物学上长期扎根的。这项提案推进了 解释这一过程的表观遗传编程假说。它假设了心理社会 与低早期SES相关的经验通过表观遗传学在基因组中编程 机制，或获得性基因组活动的变化，而不是由于DNA的变化 序列。在一项对420名志愿者的研究中，我们将评估这一假设 他们早年在低SES环境中度过，暴露在更大的家庭动荡中， 养成了警觉、悲观的人生观。我们进一步期待这些经历能够 通过表观遗传修饰嵌入免疫系统，并 从青春期开始表现为促炎表型，并持续到 成人期。这种表型的特征是促炎症转录的激活。 炎症生物标记物C-反应的控制途径和浓度增加 蛋白质和白介素6。这项工作将有助于阐明生物行为机制 自发性硬化症的差异，对预防性干预的影响。项目叙事 早年生活在贫困中的人更有可能患上 心脏病和其他疾病，当他们成年后。这项研究 该项目试图确定这种现象背后的机制。它会检查 儿童早期的贫困会改变免疫系统的运作方式， 并以一种在整个生命周期中持续存在的方式来呈现一个人 成年后易患疾病的。

PROJECT SUMMARY/ABSTRACT 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. PROJECT NARRATIVE 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.