Biomarkers of aging in a free-ranging primate population

描述(由申请人提供)：恒河猴是衰老生物医学研究的优秀动物模型，最近提倡通过合作、跨学科的方法更多地利用这些灵长类动物。在衰老研究中，恒河猴未得到充分利用的一个方面是研究与衰老相关的行为和认知、神经内分泌和免疫功能或健康和疾病的自然发生的个体间差异。这项研究的广泛目标是开始一项大规模的长期调查，研究环境和遗传决定因素在与衰老相关的健康和疾病过程中的个体间差异，在PR的卡约圣地亚哥自由放养的恒河猴种群中。本研究的具体目的是评估年龄对几种可能的躯体、代谢和神经生物衰老生物标记物的影响，并调查社会环境变量(如优势等级和社会网络大小)在多大程度上解释衰老生物标记物的个体差异。我们的假设是，在社会支持很少的低地位个体中，恒定负荷的积累可能会加剧这些个体中与衰老相关的健康问题。此外，我们假设，社会变量对衰老和健康的影响背后的神经内分泌机制可能涉及HPA轴活动的长期变化。这项研究将在两年内进行。受试者为年龄在15岁以上的女性(n=56)和对照组，年龄在5岁到15岁之间。所有受试者和对照将每年采集一次形态测量、血液样本和脑脊液样本。捕获后测量的血浆皮质醇水平将被用作应激反应的标志。血浆皮质醇对地塞米松抑制试验的反应将用于评估糖皮质激素的负反馈。将对血清样本进行血液化学变量分析，并对脑脊液样本进行CRH和单胺类代谢物的分析。所有受试者将每周接受观察，并收集粪便样本并进行皮质醇和皮质酮的检测。荷尔蒙浓度将被用作衰老生物标志物个体间差异的潜在预测因子，以及社会变量、年龄和遗传相关性。公共卫生相关性：该项目将提供有关环境、衰老和健康之间的关系以及自由放养恒河猴衰老生物标记物个体间变异性来源的新信息。这些数据将加强我们对非人类灵长类动物如何作为人类衰老模型的理解，并对适当的临床诊断和老年人护理具有启示意义。

DESCRIPTION (provided by applicant): Rhesus monkeys are excellent animal models for biomedical research on aging and a greater use of these primates through cooperative, interdisciplinary approaches has recently been advocated. One aspect of aging research in which rhesus monkeys have been under-utilized is the study of naturally occurring interindividual variation in aging-related changes in behavior ad cognition, neuroendocrine and immune function, or health and disease. The broad aim of this study is to begin a large-scale long-term investigation of the environmental and genetic determinants of interindividual variation in aging-related health and disease processes in the free-ranging rhesus monkey population on Cayo Santiago, PR. The specific aims of this study are to assess the effects of age on several putative somatic, metabolic, and neurobiological aging biomarkers and investigate the extent to which social environmental variables (e.g., dominance rank and social network size) account for interindividual variability in aging biomarkers. Our hypothesis is that the accumulation of allostatic load in low status individuals with little social support might exacerbate aging-related health problems in these individuals. Further, we hypothesize that the neuroendocrine mechanisms underlying the effects of social variables on aging and health may involve long-term changes in the activity of the HPA axis. The study will be conducted in two years. Subjects will be all females older than 15 years of age (n = 56) and a control group with individuals aged between 5 and 15 years. All subjects and controls will be captured once a year for the collection of morphological measures, blood samples, and CSF samples. Plasma cortisol levels measured after capture will be used as markers of stress responsiveness. Plasma cortisol responses to a dexamethasone suppression test will be used to assess glucocorticoid negative feedback. Serum samples will be assayed for blood chemistry variables, and CSF samples for CRH and monoamine metabolites. All subjects will be observed on a weekly basis and fecal samples will be collected and assayed for cortisol and corticosterone. Hormone concentrations will be used as potential predictors of interindividual variation in aging biomarkers along with social variables, age, and genetic relatedness. PUBLIC HEALTH RELEVANCE: This project will provide new information on the relation between environment, aging, and health as well as on the sources of interindividual variability in aging biomarkers in free-ranging rhesus monkeys. These data will enhance our understanding of how nonhuman primates may serve as models for human aging and have implications for the proper clinical diagnoses and care of the elderly as well.