Collaborative Research: Early life effects on later life biological outcomes: evolutionary and molecular mechanisms

人们出生和成长的环境可能会对他们的生物学产生深远而持久的影响，但早期生活环境因素如何以及为什么会在以后的生活中影响生理和健康仍然知之甚少。这个项目探索了早期生活对生活在与他们早期生活截然不同的环境中的群体后来生活的生物结果产生影响的机制和进化基础。由于市场一体化、文化适应和城市化的日益加剧，这些群体正在经历快速的生活方式变化，他们的见解在生物文化理论的背景下，促进了关于生命周期中生物联系的知识。鉴于许多人类群体正在经历类似的生活方式变化，该项目还可能为全球健康研究提供信息，并让我们了解美国和其他高收入国家的人们面临的一些最大健康威胁的复杂原因。这项研究为本科生、研究生和博士后以及参与其中的社区成员提供了许多科学培训机会。通过与流动诊所的伙伴关系，这项研究还直接有助于改善参与群体的卫生保健。为了揭示早期生命对后期生物结果的影响的机制和进化基础，本研究有三个总体目标。首先，研究人员使用详细的访谈和对许多行为、人体测量和生理特征的直接测量来描述研究参与者的早期生活和当前环境以及他们目前的生理状态。其次，使用这些数据和之前建立的建模方法，研究人员检验了关于早年生活对晚年健康的影响如何演变的相互矛盾的解释，包括众所周知但没有得到充分检验的“发育限制”和“预测性适应反应”假说。第三，研究人员正在使用尖端基因组技术，通过测量全基因组DNA甲基化和基因表达水平，并将这些基因组机制与它们所响应的环境刺激及其下游健康后果联系起来，来识别介导早期生活环境对以后健康影响的基因和基因调控过程。这项研究的一个特别创新和有前途的特点是，它整合了包括人类进化生物学、行为生态学、流行病学、生物医学和基因组学在内的各种科学领域的理论和方法。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The environments that people are born and raised in can have profound and long-lasting effects on their biology, but precisely how and why early life environmental factors “get under the skin” to influence physiology and health in later life remains poorly understood. This project explores the mechanistic and evolutionary bases of early life effects on later life biological outcomes in groups living in environments that are dramatically different from those they encountered early in life. Insights from such groups, who are undergoing rapid lifestyle changes due to increasing market integration, acculturation, and urbanization, advance knowledge about biological connections across the lifespan, in the context of biocultural theory. The project may also inform global health research, given that many human groups are undergoing similar lifestyle changes, as well as inform our understanding of the complex causes of some of the greatest health threats faced by people in the United States and other high-income countries. The research provides many scientific training opportunities for undergraduate, graduate, and postdoctoral students, as well as participating community members. Through partnerships with mobile clinics, this research is also directly contributing to improving health care among participating groups. In order to uncover the mechanistic and evolutionary bases of early life effects on later life biological outcomes, this research has three general goals. First, the researchers use detailed interviews and direct measurements of numerous behavioral, anthropometric, and physiological traits to characterize the early life and current environments of study participants and their current physiological status. Second, using these data and previously established modeling methods, the researchers test competing explanations for how early life effects on later life health evolve, including the well-known but insufficiently tested “developmental constraints'' and “predictive adaptive responses” hypotheses. Third, the researchers are using cutting-edge genomic techniques to identify the genes and gene regulatory processes that mediate early life environmental influences on later life health by measuring genome-wide DNA methylation and gene expression levels and linking these genomic mechanisms to both the environmental stimuli to which they are responsive and their downstream health consequences. An especially innovative and promising feature of this research is that it integrates theory and methods from a variety of scientific fields including human evolutionary biology, behavioral ecology, epidemiology, biomedicine, and genomics.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.