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

项目总结 公共卫生中最经久不衰的问题之一是，为什么一些人在晚年仍保持良好的健康 而另一些人则在健康、身体机能和幸福感方面有所下降。越来越多的证据表明 社会环境因素可能会导致个体在“生物老龄化”进程中的差异，但 我们对它们如何影响不同的身体系统缺乏清晰的理解。尽管这些问题有 在人类中很难解决，野生灵长类种群提供了独特的进步机会。 该项目的总体目标是对社会和物理环境如何产生新的见解 影响老龄化速度和健康差距的异质性。我们将通过开发一种新的 生物衰老研究的模型系统，使用基于现场的行为观察和 野生白面卷尾猴非侵入性生物样本的实验室分析。我们的长期合作 对这一物种的纵向研究使我们能够利用近40年来关于生命史的细粒度数据， 血统、社会行为，以及关于物理环境的丰富的各种相关数据。 卷尾猴与人类的共同特征，包括复杂的社会关系，杂食性，大大脑， 并延长寿命，使它们处于有利的位置，为我们自己物种的衰老和健康提供见解。 我们在开发阶段的第一个目标是识别、验证和表征衰老和 来自非侵入性生物样本的成人横断面生理和分子领域的健康状况 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 用于非侵入性生物采样，通过它我们将扩展野生动物模型集，在这些模型中 生物老化是可以研究的。第二，我们将开发新的身体功能行为评估 与常见的老年评估类似，并将社会逆境的各个方面量化为与之相关的方面 导致健康状况不佳，存活率降低，或加速人类的生物衰老。在实施阶段，我们的 目的是测试社会和自然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。为了实现这一点，我们将纵向分析 我们在发展阶段建立的生物标记物和健康评估的变化， 与我们的长期背景数据相结合。 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， 新开发的生物标记物可以在不同的身体系统和 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，我们将摆脱 对解释衰老进程中个体差异的潜在机制的新认识 因此，在了解如何延长人类活跃、健康生活的年限方面，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.