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

该奖项是NSF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的奖励包括在知名科学家的赞助下进行两年的培训，并鼓励博士后研究员进行独立研究。NSF致力于促进来自科学界各部门的科学家，包括来自代表性不足的群体的科学家参与其研究计划和活动;博士后期间被认为是实现这一目标的专业发展的重要水平。每个博士后研究员必须解决推进各自学科领域的重要科学问题。在纽约大学的James希格姆博士、亚利桑那州立大学的Noah Snyder-Mackler博士和埃克塞特大学的Lauren布伦特博士的赞助下，该博士后奖学金支持早期职业科学家调查早期生活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。在早期发育过程中暴露于社会和生态困境会对包括人类在内的各种物种的衰老、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还没有得到很好的理解。鉴于人口老龄化迅速增长，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动物的近亲，这项研究采取了比较进化的方法，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演变的理解中的重要空白，从而可以提高我们对如何解决早期生活逆境导致的人类健康差异的理解。生命早期的逆境经历可能会产生深远而持久的后果，例如增加对疾病的易感性，但人们对生命早期逆境究竟如何影响疾病和死亡前开始的身体、生理和细胞衰退的了解较少。本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种群提供了研究与衰老多个领域相关的早期生活逆境的机会。拟议的研究利用长期的人口统计学数据以及详细的行为，分子，生理和物理数据来表征每只动物在生命早期的不良经历（例如，失去父母、社会地位低、社会孤立和存在竞争性兄弟姐妹），并评估这如何预测跨领域的生存和纵向衰老。从个体收集重复的生物样品，其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、关节活动性、步态速度）。通过进行一项研究，同时从寿命的角度和一套广泛的生物标志物在成年期纵向测量，这些发现将建立一个全面的模型，早期生命的影响，作为未来研究的基础比较生物人类学和进化医学。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大于其他领域，以及某些衰老领域是否先于其他领域。这项研究的结果将有助于我们了解对早期生活逆境的反应的演变，并有助于我们理解个人年龄的差异。该奖项反映了NSF的法定使命，并通过使用基金会的智力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.