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，跨学科方法更多地使用这些灵长类动物。衰老研究的一个方面是研究自然发生的个体间差异，这些差异与衰老有关，包括行为和认知、神经内分泌和免疫功能，或健康和疾病。本研究的主要目的是开始一项大规模的长期调查，调查圣地亚哥岛自由放养的恒河猴种群中与衰老相关的健康和疾病过程中个体间差异的环境和遗传决定因素。本研究的具体目的是评估年龄对几种假定的躯体、代谢、和神经生物学衰老生物标志物，并调查社会环境变量（例如，优势等级和社会网络大小）解释了衰老生物标志物的个体间变异性。我们的假设是，积累的非稳态负荷在低地位的个人，很少的社会支持，可能会加剧这些人的衰老相关的健康问题。此外，我们推测，神经内分泌机制的社会变量对衰老和健康的影响可能涉及HPA轴的活动的长期变化。这项研究将在两年内进行。受试者将是年龄大于15岁的所有女性（n = 56）和年龄在5至15岁之间的对照组。所有受试者和对照组将每年采集一次，用于采集形态学指标、血液样本和CSF样本。捕获后测量的血浆皮质醇水平将用作应激反应的标志物。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负反馈。将对血清样本进行血液化学变量分析，并对CSF样本进行CRH和单胺代谢物分析。每周观察一次所有受试者，采集粪便样本并测定皮质醇和皮质酮。激素浓度将被用作老化生物标志物个体间变异的潜在预测因子，沿着社会变量、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、衰老和健康之间关系的新信息，以及自由放养的恒河猴衰老生物标志物的个体间变异来源。这些数据将增强我们对非人灵长类动物如何作为人类衰老模型的理解，并对老年人的适当临床诊断和护理产生影响。

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.