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

合作研究：早期生命对以后生命生物学结果的影响：进化和分子机制

• 批准号: 2142092
• 负责人: Thomas Kraft
• 金额: $ 8.97万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2142092&HistoricalAwards=false
• 关键词: Collaborative; Research; Early; life; effects

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.

人们出生和成长的环境可以对他们的生物学产生深远而持久的影响，但确切地说，早期生活的环境因素是如何以及为什么“深入人心”影响晚年的生理和健康，人们仍然知之甚少。该项目探讨了生活在与早期生活环境截然不同的环境中的群体的早期生活对后期生活生物学结果的影响的机制和进化基础。在生物文化理论的背景下，这些群体由于市场一体化、文化适应和城市化而经历着快速的生活方式变化，他们的见解推动了对整个生命周期的生物联系的认识。鉴于许多人类群体正在经历类似的生活方式改变，该项目还可能为全球健康研究提供信息，并使我们了解美国和其他高收入国家人民面临的一些最大健康威胁的复杂原因。该研究为本科生、研究生、博士后以及参与的社区成员提供了许多科学培训机会。通过与流动诊所建立伙伴关系，这项研究还直接有助于改善参与群体的保健。为了揭示早期生活对后期生活生物学结果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当前的生理状态。其次，利用这些数据和先前建立的建模方法，研究人员测试了早期生活对晚年健康演变的影响的相互竞争的解释，包括众所周知但未经充分验证的“发育限制”和“预测性适应反应”假设。第三，研究人员正在使用尖端的基因组技术，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，来确定介导早期生活环境对后期生活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各种科学领域的理论和方法，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。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。