Doctoral Dissertation Research: Identifying Plastic Responses in Human Skeletal Tissues through a Sensitive Developmental Windows Framework

环境因素对生长和发育过程有相当大的影响，在生命早期经历的压力可能会对健康和死亡风险产生长期后果。因此，了解个人何时最容易受到压力暴露是至关重要的。敏感发育窗(SDW)是生命的早期阶段，此时能量需求很高，发育中的组织对压力表现出更大的可塑性。这篇博士论文项目将使用SDW框架来研究人类骨骼系统可塑性的证据，以更好地理解早期生命中应激暴露的时机如何影响一生中疾病易感性和死亡风险的模式。这个项目的智力影响将是产生一个新的框架，在这个框架中更清楚地定义早期生命环境、生物学和整个生命周期的健康结果之间的关系。从这个项目中得出的关于发展压力的终生影响的见解可能会为人类发展和公共卫生方面的研究提供信息。该项目还将促进对本科生和研究生进行非破坏性骨骼分析方法的培训，这些方法广泛适用于现代、历史和考古学背景。这个项目将改进现有的识别和解释骨骼系统可塑性证据的方法，方法是检查一组骨骼元素的不对称性，这些不对称性反映了儿童早期发育的较长时期。可塑性的证据将通过SDW框架通过计算三个骨骼样本的不对称指数来衡量，这三个骨骼样本代表了从事不同生存模式、社会组织和饮食的人口(早期农民、史前农学家和历史上的前工业家)。这些不对称指数将在不同人群中进行比较，并使用儿童死亡率、死亡年龄和成年身高作为协变量进行评估，以便评估可塑性对整个寿命内死亡风险的影响。该项目采用的方法包括对骨骼元素进行非破坏性分析，提供了一种可访问的可塑性检查方法。该奖项反映了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。

Environmental factors exert considerable influence over processes of growth and development, and stress experienced in early life can have long-term consequences for health and mortality risk. It is therefore critical to understand when individuals are most vulnerable to stress exposures. Sensitive developmental windows (SDW) are periods in early life when energy needs are high, and developing tissues exhibit greater plasticity in response to stress. This doctoral dissertation project will examine evidence of plasticity in the human skeletal system using a SDW framework, in order to better understand how the timing of stress exposures in early life influence patterns of disease susceptibility and mortality risk over the lifespan. The intellectual impacts of this project will be the production of a novel framework in which to more clearly define the relationship between early life environments, biology, and health outcomes across the lifespan. Insights derived from this project about the lifetime impacts of developmental stress may inform research in human development and public health. The project will also facilitate training of undergraduate and graduate students in non-destructive methods of skeletal analysis that are broadly applicable across modern, historical, and archaeological contexts. This project will improve existing methods of identifying and interpreting evidence of plasticity in the skeletal system by examining a set of asymmetries in skeletal elements that capture an extended period of early child development. Evidence for plasticity will be measured through the SDW framework by calculating asymmetry indices in three skeletal samples that represent human populations engaged in different modes of subsistence, social organization, and diet (early farmers, prehistoric agriculturalists, and historic preindustrialists). These asymmetry indices will be compared across populations and assessed using childhood mortality rates, age-at-death and adult stature as covariates, so that the impact of plasticity on mortality risk over the lifespan can be evaluated. The methodology employed in this project involves non-destructive analysis of skeletal elements, providing an accessible approach to examining plasticity.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.