`Core B: Animal Core

`核心B：动物核心

• 批准号: 10201482
• 负责人: Christopher Yeh Chen
• 金额: $ 127.58万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10201482
• 关键词: 3 year old; Address; Adopted; Adrenal Glands; Age; Aging; Animal Welfare; Animals; Archives; Awareness; Behavior; Betamethasone; Biological Markers; Birth; Body Weight decreased; Brain; Calories; Cardiac; Cardiovascular system; Cell Aging; Characteristics; Corticotropin; Data; Development; Diagnostic; Doctor of Philosophy; Eating; Endocrine; Environment; Euthanasia; Event; Failure; Female; Fetal Growth; Fetal Growth Retardation; Fetus; Fibroblasts; Food; Genetic; Glucocorticoids; Goals; Hippocampus (Brain); Housing; Human; Hydrocortisone; In Vitro; Individual; Intake; Intervention; Knowledge; Lactation; Lead; Learning; Life; Life Cycle Stages; Life Expectancy; Longevity; Magnetic Resonance Imaging; Maintenance; Malnutrition; Measures; Metabolic; Metabolism; Modeling; Molecular; Mothers; Neonatal; Neuropsychological Tests; Nutrient; Organ; Paper; Papio; Pathway interactions; Patients; Perinatal; Phenotype; Physiological; Pituitary Gland; Pituitary-Adrenal System; Population; Pregnancy; Primates; Procedures; Publications; Published Comment; Publishing; Randomized; Research; Resources; Risk; Role; Skin; Social Dominance; Stress Tests; Structure; Surrogate Mothers; System; Techniques; Testing; Training; Uterus; Variant; Vertebrates; Weaning; Weight; age related; biological systems; brain behavior; data integration; experience; falls; feeding; fetal; frailty; healthspan; in vivo; indexing; insight; male; maternal obesity; mortality; nonhuman primate; nutrition; offspring; perinatal period; postnatal; pregnancy failure; pregnant; prevent; response; sex; social; sound; synergism; translation to humans; 3 year old; Address; Adopted; Adrenal Glands; Age; Aging; Animal Welfare; Animals; Archives; Awareness; Behavior; Betamethasone; Biological Markers; Birth; Body Weight decreased; Brain; Calories; Cardiac; Cardiovascular system; Cell Aging; Characteristics; Corticotropin; Data; Development; Diagnostic; Doctor of Philosophy; Eating; Endocrine; Environment; Euthanasia; Event; Failure; Female; Fetal Growth; Fetal Growth Retardation; Fetus; Fibroblasts; Food; Genetic; Glucocorticoids; Goals; Hippocampus (Brain); Housing; Human; Hydrocortisone; In Vitro; Individual; Intake; Intervention; Knowledge; Lactation; Lead; Learning; Life; Life Cycle Stages; Life Expectancy; Longevity; Magnetic Resonance Imaging; Maintenance; Malnutrition; Measures; Metabolic; Metabolism; Modeling; Molecular; Mothers; Neonatal; Neuropsychological Tests; Nutrient; Organ; Paper; Papio; Pathway interactions; Patients; Perinatal; Phenotype; Physiological; Pituitary Gland; Pituitary-Adrenal System; Population; Pregnancy; Primates; Procedures; Publications; Published Comment; Publishing; Randomized; Research; Resources; Risk; Role; Skin; Social Dominance; Stress Tests; Structure; Surrogate Mothers; System; Techniques; Testing; Training; Uterus; Variant; Vertebrates; Weaning; Weight; age related; biological systems; brain behavior; data integration; experience; falls; feeding; fetal; frailty; healthspan; in vivo; indexing; insight; male; maternal obesity; mortality; nonhuman primate; nutrition; offspring; perinatal period; postnatal; pregnancy failure; pregnant; prevent; response; sex; social; sound; synergism; translation to humans

Core B: Animal Core – Lead PI: Cun Li, MD; Multiple PI: Peter W Nathanielsz, MD, PhD Animal Core Abstract: Significance/Justification of nonhuman primate studies. Extensive separate aging and programming research exists but few studies address programming-aging interactions and none in nonhuman primates (NHP) other than our own recent publications. Baboons are the closest practical experimental species to humans. Knowledge gained will help develop new interventions to increase health span even in early life and permit diagnostic approaches to identify patients at risk of accelerated aging. Premises/hypotheses. 1. Antecedents of aging exist early in hippocampal-hypothalamo-pituitary-adrenal (HHPA) axis, brain structure and function, and behavior; cardiovascular system (CVS); metabolic biomarkers, and associated genetics. 2. Programming-aging interactions are major determinants of life course health span. 2a. Moderate perinatal maternal nutrient reduction alters HHPA axis, brain and behavior, CVS, and metabolic function evident in accelerated changes in aging biomarkers in their IUGR offspring (F1) compared to normal life course (NLC) controls receiving normal perinatal nutrition. 2b. Maternal obesity (MO) in the perinatal period alters function in the HHPA axis, brain and behavior, CVS, and metabolism evident in accelerated changes in aging biomarkers compared to NLC receiving normal perinatal nutrition. 2c. Cortisol replacement intervention to prevent the life course cortisol fall increases the rate of aging in the systems studied evident in accelerated changes in aging biomarkers compared to NLC baboons in which the NLC cortisol falls. 3. Comparing NLC control data with data from three interventions that alter the aging trajectory provides insights into key mechanisms in systems and cellular aging pathways for translation to humans to anticipate age-related mechanisms that decrease health span enabling development of human aging markers and interventions. Our studies will also provide basc information on normal organ function not obtainable in humans. Approach. We study equal male and female baboons in all groups using in vivo techniques – tether, CVS, endocrine, metabolic approaches, MRI, and in vitro studies on skin fibroblasts. Synergy. All 96 baboons undergo the same procedures allowing data integration across biological systems. Response to IRG observed weaknesses. Specifically, we removed redundancies and addressed colony lifespan variations - our goal is to start from an early age to study aging to obtain a data continuum as animals age. We describe programming models in more detail. Because of lack of enthusiasm and IRG criticisms we removed the maternal glucocorticoid group. We no longer conduct euthanasia on any animals. In the General Overview we justify the title Womb to Tomb with plans to incorporate published fetal data and new data from our fetal and postnatal archives. We present our plans to share unique resources worldwide and clearly state that all animals that have undergone a treatment have age-matched NLC group controls. The human intruder test replaces the isolation stress test. Tether maintenance is described in detail. Animal Welfare. We have experience with all procedures for over 32y.

核心B：动物核心 - 铅PI：Cun Li，医学博士；多个PI：Peter W Nathanielsz，医学博士，博士 动物核心摘要： 非人类灵长类动物研究的意义/理由。广泛的单独衰老和编程 研究存在，但很少有研究涉及编程互动，而在非人类隐私中也没有研究 （NHP）除了我们自己最近的出版物外。狒狒是最接近的实验物种 人类。获得的知识将有助于制定新的干预措施，即使在早期生活中， 允许诊断方法识别有加速衰老风险的患者。前提/假设。 1。 衰老的先例早期存在于海马 - - 海波丘脑 - 垂体 - 肾上腺（HHPA）轴，大脑结构 和功能和行为；心血管系统（CVS）;代谢生物标志物和相关遗传学。 2。 编程互动是生活课程健康跨度的主要决定者。 2a。中度围产期 孕产妇营养减少改变了HHPA轴，大脑和行为，CVS和代谢功能证据 与正常生命课程（NLC）相比 控制接受正常围产营养的控制。 2b。围产期的孕产妇肥胖（MO）在变化 HHPA轴，大脑和行为，CVS和代谢证据在衰老生物标志物的加速变化中 与NLC接受正常的围产期营养相比。 2C。皮质醇替代干预以防止生命 课程皮质醇跌落增加了在衰老变化加速变化的系统证据中的衰老率 与NLC皮质醇下降的NLC狒狒相比，生物标志物。 3。将NLC控制数据与 来自改变衰老轨迹的三种干预措施的数据提供了对系统中关键机制的见解 和细胞衰老途径，以翻译为人类，以预测与年龄相关的机制降低 健康跨度可以发展人类衰老标记和干预措施。我们的研究也将提供 BASC关于正常器官功能的信息在人类中无法获得。方法。我们研究平等男性和 所有组中使用体内技术的雌性狒狒 - 系绳，简历，内分泌方法，代谢方法，MRI， 以及对皮肤成纤维细胞的体外研究。协同作用。所有96只狒狒都接受了允许数据的相同程序 跨生物系统的集成。对IRG的反应观察到的弱点。具体来说，我们删除了 冗余和解决殖民地寿命变化 - 我们的目标是从小到学习衰老到 随着动物的年龄，获得数据连续性。我们更详细地描述编程模型。因为缺乏 热情和IRG批判主义我们消除了母体糖皮质激素。我们不再进行 任何动物的安乐死。在一般概述中，我们证明了标题子宫给坟墓的合理性 从我们的胎儿和产后档案中纳入了已发表的胎儿数据和新数据。我们提出我们的计划 在全球范围内共享独特的资源，并清楚地表明，所有接受治疗的动物都已经 年龄匹配的NLC组对照。人类入侵者测试取代了隔离应力测试。系绳 维护详细描述。动物福利。我们有超过32岁的所有程序的经验。