Effects of early life adversity on the pace of aging in rhesus macaques

该奖项是美国国家科学基金会社会、行为和经济科学博士后研究奖学金（SPRF）计划的一部分。SPRF计划的目标是为学术界、工业界或私营部门和政府的科学事业准备有前途的早期职业博士级科学家。SPRF奖励包括在知名科学家的赞助下进行为期两年的培训，并鼓励博士后进行独立研究。美国国家科学基金会寻求促进科学界各阶层的科学家，包括那些未被充分代表的群体的科学家，参与其研究项目和活动；博士后阶段被认为是实现这一目标的一个重要的专业发展阶段。每个博士后必须解决各自学科领域的重要科学问题。在纽约大学的詹姆斯·海厄姆博士、亚利桑那州立大学的诺亚·斯奈德-麦克勒博士和埃克塞特大学的劳伦·布伦特博士的赞助下，这个博士后奖学金奖支持一位早期职业科学家研究早期生活中的逆境是否会降低自由放养的恒河猴的预期寿命并加速衰老。对包括人类在内的许多物种来说，在发育早期暴露于社会和生态困境会对衰老、健康和生存产生负面影响。然而，这些早期逆境后果背后的生物学机制尚不清楚。鉴于老龄化人口的迅速增长，迫切需要确定影响老龄化速度变化的因素类型及其时间。本研究具有独特的优势，将历史数据与广泛的纵向生物采样相结合，以产生迄今为止最全面的早期生活逆境和衰老模型。此外，通过在自然环境中研究灵长类近亲，本研究采用了比较进化的方法，并增加了我们对这些早期生命效应进化的背景以及它们如何在物种和环境中变化的理解。这项研究填补了我们对人类衰老健康机制和进化的理解上的重要空白，从而可以提高我们对如何解决由早期生活逆境引起的人类健康差异的理解。早期生活中的不良经历可能会产生深远而持久的后果，比如对疾病的易感性增加，但早期生活中的逆境究竟是如何影响疾病和死亡之前开始的身体、生理和细胞衰退的，目前还不太清楚。目前的研究调查了早期生活逆境如何预测自由放养的恒河猴种群的寿命和衰老速度。没有其他非人类灵长类动物群体提供了研究与衰老多个领域相关的早期生活逆境的机会。这项拟议的研究利用长期的人口统计数据以及详细的行为、分子、生理和物理数据来描述每只动物生命早期的不良经历（例如，失去父母、社会地位低下、社会孤立和竞争兄弟姐妹的存在），并评估这些数据如何预测跨领域的生存和纵向衰老。从个体中收集重复的生物样本，包括内分泌和免疫生物标志物（例如，hpa轴功能，免疫激活，炎症），分子生物标志物（例如，DNA甲基化，端粒磨损，线粒体功能）和物理生物标志物（例如，身体状况，面部老化，关节活动能力，步态速度）。通过开展一项研究，从生命周期的角度和在成年期纵向测量一系列广泛的生物标志物，这些发现将为早期生命影响的进化建立一个全面的模型，为未来比较生物人类学和进化医学的研究奠定基础。多输出分析将确定早期生活逆境是否对某些衰老领域的影响比对其他领域的影响更大，以及某些领域的衰老是否先于其他领域。总的来说，这项研究的结果将阐明对早期生活逆境的反应的演变，并有助于我们理解个体衰老的方式和原因。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。

This award was provided as part of NSF's Social, Behavioral and Economic Sciences Postdoctoral Research Fellowships (SPRF) program. The goal of the SPRF program is to prepare promising, early career doctoral-level scientists for scientific careers in academia, industry or private sector, and government. SPRF awards involve two years of training under the sponsorship of established scientists and encourage Postdoctoral Fellows to perform independent research. NSF seeks to promote the participation of scientists from all segments of the scientific community, including those from underrepresented groups, in its research programs and activities; the postdoctoral period is considered to be an important level of professional development in attaining this goal. Each Postdoctoral Fellow must address important scientific questions that advance their respective disciplinary fields. Under the sponsorship of Dr. James Higham at New York University, Dr. Noah Snyder-Mackler at Arizona State University, and Dr. Lauren Brent at the University of Exeter, this postdoctoral fellowship award supports an early career scientist investigating whether early life adversity reduces life expectancy and accelerates aging in free ranging rhesus macaques (Macaca mulatta). Exposure to social and ecological hardships during early development can exert negative effects on aging health and survival in a wide range of species including humans. However, the biological mechanisms underlying these consequences of early adversity are not well understood. Given the rapidly growing aging-population, there is an urgent need to determine the type of factors and their timing that affect variation in the pace of aging. The present study has the unique benefit of incorporating historical data with expansive longitudinal biological sampling to produce the most comprehensive model of early life adversity and aging to date. Further, by studying a close primate relative in a naturalistic environment, this research takes a comparative evolutionary approach and adds to our understanding of the context in which these early life effects evolved and how they vary across species and environments. This research fills important gaps in our understanding of the mechanisms and evolution of human aging health and can thus improve our understanding of how to address disparities in human health stemming from early life adversity. Adverse experiences in early life can have profound lasting consequences, such as increased susceptibility to diseases, but exactly how early life adversity influences the physical, physiological, and cellular declines that begin prior to disease and death is less understood. The present research investigates how early life adversity predicts lifespan and the pace of aging in a population of free ranging rhesus macaques. No other population of nonhuman primates offers the opportunity to study early life adversity in relation to multiple domains of aging. The proposed study capitalizes on long-term demographic data alongside detailed behavioral, molecular, physiological, and physical data to characterize each animal’s adverse experiences early in life (e.g., parental loss, low social status, social isolation, and presence of a competing sibling) and evaluate how this predicts survival and longitudinal aging across domains. Repeated biological samples are collected from individuals, which include endocrine and immune biomarkers (e.g., HPA-axis function, immune activation, inflammation), molecular biomarkers (e.g., DNA methylation, telomere attrition, mitochondrial function), and physical biomarkers (e.g., body condition, facial aging, joint mobility, gait speed). By conducting a study with both a lifespan perspective and an expansive set of biomarkers measured longitudinally across adulthood, these findings will establish a comprehensive model for the evolution of early life effects, as a foundation for future research in comparative biological anthropology and evolutionary medicine. The multi-output analyses will identify whether early life adversity affects some domains of aging more than others and if some domains of aging precede others. Together the results of the proposed study will shed light on the evolution of responses to early life adversity, and contribute to our understanding of how and why individuals age differently.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.