A life course perspective on the effects of cumulative early adversity on health

摘要 早期生命的长臂仍然是人类健康中最持久的谜题之一。到目前为止，有两个班级 已经提出了许多进化模型来解决这个难题。发展约束模型提出 早期的逆境导致在发展过程中与躯体投资的权衡，而长期的负面投资 对健康的影响。预测模型提出，生物体利用早期的逆境来预测未来。 环境，进行发展调整，以优化达尔文的健康在成年。相对的 这些模型的优点一直很难确定，特别是在人类和其他长寿物种中。 解决这一争论对于理解健康和疾病的发展起源以及 找出有效的方法来减轻早年生活的影响。 该提案的主要目标是通过以下特征来测试预测和约束框架 不同的发展，健康，健身和衰老相关的结果产生的早期生活逆境的变化。 它在非人类灵长类动物模型中实现了这一目标，该模型提供了一个很好的比较系统 了解早期人类面临的进化压力。该系统还提供了实时数据 早期逆境的几种形式和多种纵向发展、行为和健康结果 对早期逆境的反应。这个项目测试了以下中心假设：(I)对早期逆境的反应是 以发育限制为主，导致躯体投资受限，生殖延迟 时间表、低生育率和加速老龄化；但(Ii)这些反应可以通过积极的社会反应来缓解 成年后的状况。目的1区分青少年时期的制约因素和预测性反应。目标2 通过测试成人的低反应和高反应，对预测性和约束性模型进行了强有力的测试 优质的环境。AIM 3测试了社会支持的潜力，以减轻早期 逆境，提供了在成年后改善这些影响的途径。 通过跨越逆境的多个来源以及身体和生殖健康的多个方面，这 项目将提供最全面的测试来区分预测框架和约束框架 到目前为止的物种。确定哪种模式占主导地位对于预测成年后的环境将如何是至关重要的 与早期逆境互动以塑造成人健康，以及如何最好地缓解对早期逆境的反应。 具体地说，约束模型预测，缓解应侧重于早期生活。与之形成对比的是预测模型 假设最优缓解策略将根据个人早期逆境的来源而有所不同 经验丰富。通过理清对逆境的反应，这个项目将提高对 健康和疾病的发育起源，并提供了对不同逆境来源的关键洞察 成年期的好的和坏的条件相互作用，塑造成人的健康和衰老的速度。

Summary The long arm of early life remains one of the most enduring puzzles in human health. To date, two classes of evolutionary models have been proposed to address this puzzle. Developmental constraints models propose that early adversity leads to tradeoffs with somatic investment during development, with long-term, negative consequences for health. Predictive models propose that organisms use early adversity to predict future circumstances, making developmental adjustments that optimize Darwinian fitness in adulthood. The relative merits of these models have been difficult to establish, especially in humans and other long-lived species. Resolving this debate is necessary to understand the developmental origins of health and disease and to identify efficient methods to mitigate early life effects. The primary objective of this proposal is to test predictive and constraints frameworks by characterizing diverse developmental, health, fitness, and aging-related outcomes arising from variation in early life adversity. It accomplishes this objective in a non-human primate model that is offers an excellent comparative system to understand the evolutionary pressures faced by early humans. This system also offers real-time data on several forms of early adversity and multiple longitudinal developmental, behavioral, and health outcomes in response to early adversity. This project tests the central hypotheses that: (i) responses to early adversity are dominated by developmental constraints, leading to restricted somatic investment, delayed reproductive schedules, lower fertility, and accelerated aging; but (ii) these responses can be mitigated by positive social conditions in adulthood. Aim 1 distinguishes constraints and predictive responses in the juvenile period. Aim 2 contributes a strong test of predictive and constraints models by testing adult responses in both low and high quality environments. Aim 3 tests the potential for social support to mitigate the negative effects of early adversity, offering avenues to ameliorate these effects in adulthood. By spanning multiple sources of adversity and multiple aspects of somatic and reproductive health, this project will contribute the most comprehensive test to distinguish predictive and constraints frameworks in any species to date. Establishing which model dominates is critical to predict how environments in adulthood will interact with early adversity to shape adult health, and how to best mitigate responses to early adversity. Specifically, constraints models predict that mitigation should focus on early life. In contrast predictive models posit that optimal mitigation strategies will differ depending on which sources of early adversity individuals experienced. By disentangling responses to adversity, this project will improve basic understanding of the developmental origins of health and disease and lend key insight into how different sources of adversity interact with good and bad conditions in adulthood to shape adult health and rates of aging.