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.

项目摘要 生命课程理论强调，衰老是一种开始的轨迹，因此，个人 衰老中的异质性植根于健康暴露和我们生活的环境的一生。这 观点对于了解老年人健康不平等的性质和修改性至关重要。 但是，由于漫长的 学习人类所需的时间范围以及操作人类相关特征的困难 环境。我们建议可以通过研究未使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，旨在研究衰老的生物学 黑猩猩，我们最亲密的亲戚之一，也是重建人类衰老的关键联系 过程进化。这种紧密的进化关系导致遗传和生理相似性 不由普通实验室动物模型表示。黑猩猩是社会复杂的，长寿， 这意味着它们特别适合研究环境因素如何等待等慢性负担 感染，社会支持和社会不平等会在一生中产生健康影响。在我们的第一个资金时期， 我们验证了健康和衰老的非侵入性生物标志物的鲁棒工具包，并使用了纵向采样 黑猩猩确定黑猩猩的老化过程与人类的比较。在续签时期， 我们通过解决纵向健康数据的多维性来基于这些成功。目标1意志 扩展我们原始样品的纵向健康监测和生物采样，并将样本增加到A 总共350次野外和200个自由行的黑猩猩。我们还将开发可访问的资源以进行比较 老化研究。 AIM 2将研究以下假设 衰老中个体异质性的显着决定因素。免疫系统在 衰老过程，并在衰老的其他方面具有复杂的反馈。然而，人类的寿命很长 在对免疫系统持续挑战的环境中演变而来的。在野外 黑猩猩，我们可以在系统中研究这些动态，而无需医疗干预以及其他年龄 相关病理很少。 AIM 3通过研究社会过程的假设来建立目标2 修改衰老轨迹。我们对了解社会的机制特别感兴趣 从成年初开始的支持和地位，当他们首次建立时，他们会为以后的生活健康做出贡献 差异以及这些影响是否可以通过与年龄相关的社会行为转变进一步改变。 在我们的研究中，黑猩猩在大多数或全部成年的生活中都受到了仔细观察 难得的机会，将客观，详细的社会历史应用于不存在重大的衰老的研究 使人类研究复杂化的生活方式因素。