Developmental Consequences of Early Life Adversity

该项目将调查早期的逆境如何影响以后的生活。研究人员将研究早期逆境的负面影响是否以及如何代代相传。该项目将加强对早期逆境产生负面发育后果的表观遗传过程的基本理解，并将扩大对这种表观遗传变化在代际传递的潜力的认识。最终目标和更广泛的影响是揭示潜在的传播机制，以激发新的政策方法，旨在减少并可能扭转早期生活逆境的长期有害影响。暴露在环境因素下会影响到一个人的皮肤，改变一个人的基因功能。人们对基因功能的变化如何解释早期逆境和后来结果之间的联系越来越感兴趣。此外，对于这些功能上的变化是否可以逆转，或者它们是否可以代代相传，人们知之甚少。研究人员将利用已有的健康和行为结果数据，以及从多代不同饲养的猕猴中获得的已有的生物/遗传样本，探索将早期逆境与以后生活中的后续结果联系起来的机制和发育过程。目的是研究早期逆境的发育后果和潜在的表观遗传机制；并测试逆境的代际传递。由于猕猴93%的基因组与人类相同，这项研究将有助于阐明早期生活中的逆境如何影响人类后来的结果。将分析DNA的甲基化谱，并提取RNA以检查基因表达。研究人员将进行生物信息学分析，以评估差异表达基因集的生物学特征。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The project will investigate the pathways by which early adversity affects outcomes later in life. Investigators will examine whether and how negative consequences of early adversity may be transmitted across generations. The project will enhance basic understanding of the epigenetic processes by which early adversity generates negative developmental consequences, and it will expand knowledge about the potential for such epigenetic changes to be transmitted interegenerationally. The ultimate goal, and broader impact, is to shed new light on underlying mechanisms of transmission, in order to inspire new policy approaches aimed at reducing, and potentially reversing, long-term deleterious effects of early life adversity.Exposure to environmental factors can get under one's skin and alter how one's genes function. There is growing interest in how changes in gene functionality may account for the association between early adversity and later outcomes. Moreover, little is known about whether those changes in functionality can be reversed or whether they can be transmitted across generations. Using pre-existing data on health and behavioral outcomes as well as pre-existing biological/genetic samples obtained from multiple generations of differentially reared macaques, investigators will explore mechanisms and developmental processes involved in linking early adversity to subsequent outcomes later in life. The goals are to examine the developmental consequences of early adversity and underlying epigenetic mechanisms; and to test the intergenerational transmission of adversity. Because macaques share 93% of their genome with humans, the study will help clarify how early life adversity affects later outcomes in humans. The methylation profile of DNA will be analyzed, and RNA will be extracted in order to examine gene expression. Investigators will conduct bioinformatics analyses to assess biological characteristics of differentially expressed gene sets.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.