A new model system for assessing the socio-environmental determinants of the pace of aging: leveraging a long-term study of wild capuchins

项目摘要 公共卫生领域最持久的问题之一是为什么有些人到老年仍保持良好的健康 而另一些人则经历健康、身体功能和幸福感的下降。越来越多的证据表明， 社会环境因素可能导致“生物老化”进程中的个体差异，但 我们对它们如何影响不同的身体系统缺乏清晰的理解。虽然这些问题 灵长类动物的野生种群为人类的进步提供了独特的机会。 这个项目的首要目标是产生新的见解如何社会和物理环境 影响老龄化率和健康差异的异质性。我们将通过开发新的 生物老化研究的模型系统，使用基于现场的行为观察和 实验室分析野生白脸卷尾猴的非侵入性生物样本。我们的长期 对这一物种的纵向研究使我们能够利用近40年来关于生活史的颗粒数据， 谱系、社会行为以及丰富的物理环境相关数据。 卷尾猴与人类共有的特征，包括复杂的社会关系，杂食性，大大脑， 和延长寿命，使它们能够很好地为我们自己物种的衰老和健康提供见解。 我们开发阶段的第一个目标是识别、验证和表征衰老的生物标志物， 健康在生理和分子领域从非侵入性生物样品在一个横截面的成人 已知年龄的卷尾猴（6-27岁）。我们一直处于开发尖端技术的前沿 非侵入性生物采样，通过它，我们将扩大野生动物模型的集合， 可以研究生物老化。其次，我们将开发新的身体功能行为评估， 是常见的老年评估的类似物，并量化与相关社会逆境平行的社会逆境方面。 健康状况不佳，生存率降低或加速人类的生物衰老。在实施阶段，我们的 目的是测试社会和物理环境对健康和老龄化轨迹的贡献， 生命历程，包括这些关系中的性别差异。为此，我们将分析纵向 我们在开发阶段建立的生物标志物和健康评估的变化， 结合我们的长期背景数据。 通过这项研究的结论，我们将建立一个创新的野生动物健康和衰老模型， 新开发的生物标志物，可在不同身体系统的特殊范围内跟踪衰老过程， 扩展表型通过将这些新措施与我们出色的长期数据相结合， 新的光的潜在机制，解释个体差异的进展，老化，并在做 因此，在了解如何延长人类活跃健康的寿命方面迈出了重要的一步。

PROJECT SUMMARY One of the most enduring questions in public health is why some individuals retain good health into old age while others experience declines in health, physical function, and wellbeing. Growing evidence indicates that socio-environmental factors can contribute to individual differences in the progression of ‘biological aging’, yet we lack a clear understanding of how they influence different body systems. Although these questions have been difficult to address in humans, wild populations of primates offer unique opportunities for progress. This project’s overarching objective is to generate new insights into how social and physical environments influence heterogeneity in rates of aging and health disparities. We will accomplish this by developing a new model system for the study of biological aging, using a combination of field-based behavioral observation and laboratory analyses of noninvasive biological samples from wild white-faced capuchins. Our long-term longitudinal study of this species allows us to leverage almost 40 years of granular data on life-histories, pedigrees, and social behavior, as well as a rich assortment of associated data on the physical environment. The traits that capuchins share with humans, including complex social relationships, omnivory, large brains, and extended longevity, make them well-situated to provide insights into aging and health in our own species. Our first Aim for the Development Phase is to identify, validate, and characterize biomarkers of aging and health in physiological and molecular domains from non-invasive biological samples in a cross-section of adult capuchins of known ages (6-27 years). We have been at the forefront of developing cutting-edge techniques for noninvasive biological sampling, through which we will expand the set of wild animal models in which biological aging can be studied. Second, we will develop new behavioral assessments of physical function that are analogs of common geriatric assessments, and quantify aspects of social adversity parallel to those linked to poor health, reduced survival, or accelerated biological aging in humans. In the Implementation Phase, our Aim is to test the contributions of social and physical environments to trajectories of health and aging across the life course, including sex differences in these relationships. To accomplish this, we will analyze longitudinal variation in the biomarkers and health assessments that we establish during the Development Phase, in combination with our long-term contextual data. By the study’s conclusion, we will have established an innovative wild animal model of health and aging, with newly developed biomarkers to track aging processes in an exceptional breadth of different body systems and extended phenotypes. By integrating these new measures with our outstanding long-term data, we will shed new light on potential mechanisms that explain individual differences in the progression of aging, and in doing so, take an important step toward understanding how to extend the years of active, healthy life in humans.