Biomarkers of aging in a free-ranging primate population

自由放养的灵长类动物种群中衰老的生物标志物

• 批准号: 7459460
• 负责人: DARIO MAESTRIPIERI
• 金额: $ 13.9万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7459460
• 关键词: 15 year old; Accounting; Adult; Advocate; Affect; Age; Age-Years; Aggressive behavior; Aging; Aging-Related Process; Animal Model; Behavior; Biological Assay; Biological Markers; Biomedical Research; Blood Chemical Analysis; Blood specimen; CRH gene; Caring; Chronic Disease; Classification; Cognition; Collection; Control Groups; Corticosterone; Corticotropin-Releasing Hormone; Data; Disease; Elderly; Environment; Exhibits; Feedback; Female; Genetic; Genetic Determinism; Glucocorticoids; Health; Hormones; Human; Hydrocortisone; Impairment; Individual; Investigation; Longevity; Macaca mulatta; Measures; Mediating; Metabolic; Modeling; Monkeys; Neurobiology; Neurosecretory Systems; Numbers; Plasma; Population; Primates; Process; Public Health; Range; Research; Role; Sampling; Serum; Social Network; Social support; Societies; Source; Stress; Testing; Variant; age effect; age related; allostatic load; base; clinical Diagnosis; dexamethasone suppression test; hypothalamic-pituitary-adrenal axis; immune function; improved; information gathering; interdisciplinary approach; monoamine; nonhuman primate; response; size; social

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.

描述（由申请人提供）：最近提倡通过合作，跨学科的方法对衰老的生物医学研究进行生物医学研究的出色动物模型。衰老研究的一个方面是，恒河猴的利用不足，是研究与衰老相关的行为认知，神经内分泌和免疫功能或健康和疾病的行为认知，神经内分泌和免疫功能的自然间个体差异。这项研究的广泛目的是开始对自由放映的恒河猴猴子种群中Cayo Santiago的自由晶状体猴子的衰老健康和疾病过程中个体差异的环境和遗传决定因素进行大规模的长期研究。这项研究的具体目的是评估年龄对几种推定的体细胞，代谢和神经生物学老化生物标志物的影响，并研究社会环境变量（例如，优势等级和社交网络规模）在衰老生物标志物中的间隔变化程度。我们的假设是，在社会支持很少的情况下，在低地位的人群中的同性恋负荷的积累可能会加剧这些人与衰老有关的健康问题。此外，我们假设社会变量对衰老和健康影响的影响的神经内分泌机制可能涉及HPA轴活动的长期变化。该研究将在两年内进行。受试者将是15岁以上的女性（n = 56），一个对照组，年龄在5至15岁之间。所有受试者和对照将每年捕获一次，以收集形态学措施，血液样本和CSF样本。捕获后测得的血浆皮质醇水平将用作应力反应性的标志。血浆皮质醇对地塞米松抑制测试的反应将用于评估糖皮质激素的负反馈。血清样品将用于血液化学变量，以及CSF样品的CRH和单胺代谢物。将每周观察所有受试者，并将收集并分析皮质醇和皮质酮的粪便样品。激素浓度将用作衰老生物标志物中个体变异的潜在预测因子，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，衰老与健康之间以及自由放映恒河猴衰老生物标志物中个体差异的来源的新信息。这些数据将增强我们对非人类灵长类动物如何作为人类衰老的模型的理解，并对老年人的适当临床诊断和护理产生影响。