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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

基本信息

批准号：
10620827
负责人：
Ian Gilby
金额：
$ 62.2万
依托单位：
UNIVERSITY OF NEW MEXICO
依托单位国家：
美国
项目类别：
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/10620827
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 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 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 disparities social influence social integration social observations social vulnerability stressor study population success theories urinary virtual

项目摘要

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.

项目总结生命历程理论强调，衰老是一个在生命早期就开始的轨迹，因此，个人老龄化的异质性植根于一生的健康暴露和我们生活的环境。这视角对于理解老年人健康不平等的性质和可修复性至关重要。然而，由于长期的原因，将生命历程的观点付诸实践是非常困难的研究人类所需的时间框架和实现人类相关特征的难度环境。我们认为，这些问题可以通过研究一个未得到充分利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，我们现存最亲密的近亲之一，也是重建人类如何衰老的关键环节流程不断演变。这种密切的进化关系导致了遗传和生理上的相似之处不是由普通的实验动物模型代表的。黑猩猩是复杂的社会和长寿的，这意味着它们特别适合于研究环境因素，如慢性负担感染、社会支持和社会不平等会在一生中产生健康影响。在我们的第一个资助期，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，并使用了以确定黑猩猩的衰老过程与人类相比如何。在续约期内，我们在这些成功的基础上，解决了我们纵向健康数据的多维问题。目标1将扩大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只自由活动的黑猩猩。我们还将开发可利用的资源，以进行比较老龄化研究。目标2将检验这一假设，即一生中感染的累积负担是老龄化中个体异质性的显著决定因素。免疫系统在这一过程中起着关键作用。衰老过程，对衰老的其他方面具有复杂的反馈作用。然而，人类的长寿在对免疫系统的传染性挑战持续存在的环境中进化。在野外黑猩猩，我们可以在没有医学干预的系统中研究这些动态，在那里其他年龄的人- 相关的病理很少见。目标3建立在目标2的基础上，通过检验社会过程的假设修改老化轨迹。我们特别感兴趣的是了解社会成年初期的支持和地位有助于他们日后的健康差异，以及这些影响是否可以通过与年龄相关的社会行为变化来进一步改变。我们研究种群中的黑猩猩在其成年生活的大部分或全部时间都被密切观察，提供这是一个难得的机会，可以将客观、详细的社会史应用于老龄化研究，而不是主要的使人类研究复杂化的生活方式因素。

项目成果

期刊论文数量（61）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Demographic and hormonal evidence for menopause in wild chimpanzees.

野生黑猩猩绝经的人口统计学和荷尔蒙证据。

DOI：
10.1126/science.add5473
发表时间：
2023
期刊：
Science (New York, N.Y.)
影响因子：
0
作者：
Wood,BrianM;Negrey,JacobD;Brown,JanineL;Deschner,Tobias;Thompson,MelissaEmery;Gunter,Sholly;Mitani,JohnC;Watts,DavidP;Langergraber,KevinE
通讯作者：
Langergraber,KevinE

Wild Chimpanzees Show a Decrease in Pant Grunting over Their First 6 Years of Life.

野生黑猩猩在生命的前六年中喘气的次数有所减少。