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

长寿灵长类动物模型中的累积生命过程对衰老和健康的影响

• 批准号: 10443110
• 负责人: Ian Gilby
• 金额: $ 67.2万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10443110
• 关键词: Accreditation; Address; Adult; Africa; African; Age; Aging; Biological; Biological Markers; Biological Models; Biology of Aging; Blood; Caring; Chronic; Clinical; Collaborations; Communities; Complex; Costs and Benefits; Custom; Data; Data Set; Databases; Dimensions; Disease; Education; Elderly; Environment; Environmental Exposure; Environmental Risk Factor; Evolution; Exposure to; Feces; Feedback; Female; Funding; Genetic; Health; Health Status; Health Surveys; Human; Human Biology; Immune system; Individual; Infection; Inflammation; Intervention; Laboratories; Laboratory Animal Models; Life; Life Cycle Stages; Life Style; Link; Longevity; Longitudinal Studies; Measures; Mediating; Medical; Methods; Modeling; Monitor; Nature; Outcome; Oxidative Stress; Pan Genus; Parasitic infection; Pathology; Pattern; Phase; Physical environment; Physiological; Physiology; Plant Roots; Play; Population; Primates; Process; Recording of previous events; Research; Resources; Role; Sampling; Shapes; Smoking; Social Behavior; Social Environment; Social Interaction; Social Network; Social Processes; Social status; Social support; Stress; System; Tanzania; Testing; Time; Translating; Uganda; Urine; Variant; Virus Diseases; age related; aged; biobank; comparative; data access; data mining; emerging adult; experience; health data; health disparity; health inequalities; healthy aging; high dimensionality; human disease; human model; immunosenescence; individual variation; infection burden; interest; lifestyle factors; male; mortality; novel; senescence; social; social attachment; social inequality; social influence; social integration; social observations; social vulnerability; stressor; study population; success; theories; urinary; virtual

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.

项目概要 生命历程理论强调衰老是一个从生命早期就开始的轨迹，因此，个体 衰老的异质性根源于我们一生的健康暴露和我们生活的环境。这 观点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，由于长期的原因，将生命历程观点付诸实践是极其困难的。 研究人类所需的时间框架以及实施人类相关特征的难度 环境。我们建议可以通过研究未充分利用的模型系统来纠正这些问题， 黑猩猩。这项研究扩展了一项纵向研究，旨在调查衰老的生物学 黑猩猩是我们现存的近亲之一，也是重建人类衰老过程的关键环节 过程进化了。这种密切的进化关系导致了遗传和生理上的相似性 不以常见的实验动物模型为代表。黑猩猩具有复杂的社会性并且寿命很长 这意味着它们特别适合研究环境因素（例如慢性负担）如何 感染、社会支持和社会不平等会对一生的健康产生影响。在我们的第一个资助期内， 我们验证了一个强大的健康和衰老非侵入性生物标志物工具包，并使用了纵向采样 黑猩猩，以确定黑猩猩的衰老过程与人类相比如何。在更新期间， 我们通过解决纵向健康数据的多维性问题，在这些成功的基础上再接再厉。目标1将 扩展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 共有 350 只野生黑猩猩和 200 只散养黑猩猩。我们还将开发可利用的资源以进行比较 衰老研究。目标 2 将检验以下假设：一生中感染的累积负担是 衰老过程中个体异质性的重要决定因素。免疫系统在其中发挥着关键作用 衰老过程并对衰老的其他方面有复杂的反馈。然而人类的寿命却很长 在免疫系统持续受到感染性挑战的环境中进化。在野外 黑猩猩，我们可以在没有医疗干预的系统中研究这些动态，而其他年龄- 相关病理很少见。目标 3 建立在目标 2 的基础上，通过检验社会过程的假设 改变衰老轨迹。我们特别感兴趣的是了解社会的机制 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改变。 我们研究群体中的黑猩猩在成年后的大部分或全部时间都受到密切观察，提供了 在缺乏专业知识的情况下，将客观、详细的社会历史应用于老龄化研究的难得机会 生活方式因素使人类研究变得复杂。