Cumulative Life Course Effects on Aging and Health in a Long-Lived Primate Model

项目摘要 生命历程理论强调，衰老是一个在生命早期开始的轨迹，因此，个体 老龄化的异质性植根于我们一生中的健康暴露和我们生活的环境。这 这一视角对于理解老年人健康不平等的性质和可改变性至关重要。 然而，由于长期以来， 研究人类所需的时间框架以及将人类的相关特征操作化的困难 环境.我们建议，这些问题可以通过研究一个未充分使用的模型系统来纠正， 黑猩猩这项研究扩展了一项纵向研究，旨在调查老年人的生物学， 黑猩猩是人类现存的近亲之一，也是重建人类衰老过程的关键环节。 过程演变。这种密切的进化关系导致了遗传和生理上的相似性， 没有常见的实验室动物模型。黑猩猩的社会性很复杂，而且寿命很长， 这意味着它们特别适合研究环境因素如何影响人类的健康， 感染、社会支持和社会不平等会对人的一生产生健康影响。在我们的第一个融资期， 我们验证了健康和衰老的非侵入性生物标志物的强大工具包， 黑猩猩来确定黑猩猩的衰老过程与人类的比较。在续约期间， 我们通过处理我们纵向卫生数据的多层面性，在这些成功的基础上再接再厉。目标1将 延长我们原始样本的纵向健康监测和生物采样，并将样本增加到 总共有350只野生黑猩猩和200只自由放养的黑猩猩。我们还将开发可获得的资源， 老化研究目标2将检验以下假设，即一生中感染的累积负担是一个 衰老中个体异质性的重要决定因素。免疫系统在免疫系统中起着关键作用。 衰老过程中，并有复杂的反馈对其他方面的衰老。然而，人类的长寿 在对免疫系统的感染性挑战持续存在的环境中进化。野生 黑猩猩，我们可以在一个没有医疗干预的系统中研究这些动态，而其他年龄的人- 相关的病理是罕见的。目标3建立在目标2的基础上，通过检验社会过程 改变衰老轨迹我们特别感兴趣的是了解社会 从成年早期开始的支持和地位，当它们第一次建立时，有助于以后的生活健康 差异，以及这些影响是否可以通过与年龄相关的社会行为变化进一步修改。 我们研究种群中的黑猩猩在成年后的大部分或全部时间里都被密切观察， 这是一个难得的机会，可以在缺乏主要研究的情况下，将客观、详细的社会历史应用于老龄化研究。 使人类研究复杂化的生活方式因素。

PROJECT SUMMARY Life course theory emphasizes that aging is a trajectory that starts early in life, and as such, individual heterogeneity in aging is rooted in a lifetime of health exposures and the environments in which we live. This perspective is critical for understanding the nature and modifiability of health inequalities among the aged. However, it has been extraordinarily difficult to put life course perspectives into practice, owing to the long timeframes necessary to study humans and the difficulty of operationalizing relevant features of human environments. We propose that these problems can be rectified by studying an underused model system, chimpanzees. This research extends a longitudinal study aimed at investigating the biology of aging in chimpanzees, one of our closest living relatives and a critical link for reconstructing how the human aging process evolved. This close evolutionary relationship results in genetic and physiological similarities that are not represented by common laboratory animal models. Chimpanzees are socially-complex and long-lived, meaning that they are particularly well suited to study how environmental factors such as the chronic burden of infection, social support, and social inequality yield health effects across a lifetime. In our first funding period, we validated a robust toolkit of non-invasive biomarkers of health and aging and used longitudinal sampling of chimpanzees to establish how the chimpanzee aging process compares with humans. In the renewal period, we build on those successes by addressing the multidimensionality of our longitudinal health data. Aim 1 will extend the longitudinal health monitoring and biosampling of our original sample and increase the sample to a total of 350 wild and 200 free-ranging chimpanzees. We will also develop accessible resources for comparative aging research. Aim 2 will examine the hypothesis that the cumulative burden of infection across life is a significant determinant of individual heterogeneity in aging. The immune system plays a pivotal role in the aging process and has complex feedbacks on other aspects of senescence. Yet, the long lifespans of humans evolved in environments where infectious challenges to the immune system were persistent. In wild chimpanzees, we can study these dynamics in a system without medical intervention and where other age- related pathologies are rare. Aim 3 builds upon Aim 2 by examining the hypothesis that social processes modify aging trajectories. We are particularly interested in understanding the mechanisms by which social support and status from early adulthood, when they are first established, contribute to later life health disparities, and whether these impacts can be further modified by age-related shifts in social behavior. Chimpanzees in our study populations have been closely observed for most or all of their adult lives, providing a rare opportunity to apply objective, detailed social histories to the study of aging in the absence of major lifestyle factors that complicate human studies.