Project 1: Developmental Programming and Aging Interactions in Primate Brain and Glucocorticoid Function.
项目 1:灵长类动物大脑和糖皮质激素功能的发育规划和衰老相互作用。
基本信息
- 批准号:10450801
- 负责人:
- 金额:$ 27.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-30 至 2023-08-15
- 项目状态:已结题
- 来源:
- 关键词:AcclimatizationAddressAdrenal GlandsAdultAgeAgingAnestheticsAnimalsBehaviorBeveragesBiological MarkersBirthBloodBlood flowBody Weight decreasedBody fatBrainBrain imagingBreedingCaloriesCarbohydratesCell AgingCell Culture TechniquesCognitionConsciousControl GroupsDataDevelopmentDietEatingEnvironmentEvaluationExplosionFailureFatty acid glycerol estersFeedbackFemaleFetal Growth RetardationFetusFoodFoxesFructoseFundingGeneral AnesthesiaGlucocorticoidsGlucoseGoalsHippocampus (Brain)HistologyHousingHumanHydrocortisoneImpaired cognitionIndividualInfusion proceduresIntakeInterventionIsotopesLactationLeadLettersLifeLife Cycle StagesLongevityMagnetic Resonance ImagingMeasuresMediatingMetabolic Clearance RateMetabolismModelingMothersNeonatalNuclearNulliparityNutrientObesityOutcomeOutcome StudyPaperPapioPathway interactionsPerinatalPeripheralPhenotypePituitary GlandPlasmaPregnancyPregnancy OutcomePrimatesProceduresProductionPublicationsPublishingRandomizedResearch PersonnelResourcesSalmonSkinSolidStressStructureSurrogate MothersSystemTechniquesTimeUterusVariantVasopressinsWeaningWeightWomanage relatedaging brainawakebasebrain behaviorbrain magnetic resonance imagingcognitive testingdietary controldrinking waterexperiencefallsfeedingfetalhealthspanin vivoinnovationinsightmalematernal obesitymother nutritionnonhuman primatenutritionobese mothersoffspringperinatal periodpregnantprogramsreceptorreproductiveresponsesextissue archivetranslation to humans
项目摘要
Project 1: Developmental Programming and Aging Interactions in Primate Brain and Glucocorticoid
Function
Lead PI: Peter Nathanielsz; Multiple PIs: Cun Li, Peter Fox
ABSTRACT
Controlled translational animal studies are needed to determine how developmental programming-aging
interactions by glucocorticoid (GC- cortisol) and other mechanisms, e.g. blood flow and metabolism, influence
brain aging and cognitive decline. Evidence supports early blood GC changes and activity and other
antecedents of aging. The Barker programming hypothesis states responses to specific challenges in critical
developmental time windows alter the developmental trajectory with persistent effects on phenotype.
Preliminary data. We 1) confirmed a linear baboon plasma cortisol fall starting at 6y age (human ~15y) and
showed a fall in paraventricular nuclear (PVN) vasopressin and increased GC receptor (GR), potential
mechanisms for the fall (increased feedback and decreased PVN drive); 2) peripheral cortisol production; and
3) GR and blood flow changes with aging.
Premises. 1. Aging antecedents are present early in the hippocampal-hypothalamo-pituitary (HHPA) axis,
brain function, and behavior. 2a. Moderate perinatal global nutrient reduction-induced IUGR alters HHPA, brain
structure and function, and behavior, evident in changes in IUGR offspring (F1) aging biomarkers compared to
controls who received normal perinatal nutrition. 2b. Maternal obesity (MO) in the perinatal period alters HHPA,
brain structure and function, and behavior, evident in changes in aging biomarkers in MO F1 vs. controls who
received normal perinatal nutrition. 2c. Cortisol replacement from 13y to maintain cortisol at 5y levels increases
the HHPA, brain, and behavior rate of aging, evident in changes in HHPA and brain-related aging biomarkers
vs. controls. 3. Comparing normative, life course observational control data with data from interventions that
alter the aging trajectory provides insights into key mechanisms in systems and cellular aging pathways. Data
will provide information for translation to humans to anticipate age-related mechanisms that both increase and
decrease health span, enabling development of markers and interventions in human aging
Approach. We study 96 baboons over 24-68% of the life course, equal males and females. Groups: 1. Normal
life course; 2. IUGR (F1) of 30% globally food reduced mothers; 3. F1 of over-nourished, obese mothers; 4.
Cortisol Replacement Intervention beginning at 13y to maintain baboons' cortisol at 5y old levels for 5 years to
address cortisol regulated mechanisms. We conduct awake, tether studies, 24h rhythms, HHPA suppression
and stimulation, MRI, brain histology, and cognitive tests to relate phenotype to cellular pathways. No baboons
are euthanized. We integrate our fetal and adult tissue archives with in vivo studies. Innovation. We propose a
new framework to understand aging based on programming-aging interactions. Environment. With our funds,
we built our outdoor holding facilities and assembled 96 baboons. We share nonhuman primate (NHP)
resources worldwide (see letters). Investigators are experienced in aging and programing NHP studies. New
to this Project, Dr. Fox brings brain-imaging and Dr. Salmon powerful cell culture approaches.
项目1:灵长类动物大脑和糖皮质激素的发育规划和衰老相互作用
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
PETER W. NATHANIELSZ其他文献
PETER W. NATHANIELSZ的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('PETER W. NATHANIELSZ', 18)}}的其他基金
Project 1: Developmental Programming and Aging Interactions in Primate Brain and Glucocorticoid Function.
项目 1:灵长类动物大脑和糖皮质激素功能的发育规划和衰老相互作用。
- 批准号:
10201487 - 财政年份:2018
- 资助金额:
$ 27.74万 - 项目类别:
Stable isotope evaluation of the methionine cycle in undernourished pregnancy
营养不良妊娠中蛋氨酸循环的稳定同位素评估
- 批准号:
8986457 - 财政年份:2015
- 资助金额:
$ 27.74万 - 项目类别:
Stable isotope evaluation of the methionine cycle in undernourished pregnancy
营养不良妊娠中蛋氨酸循环的稳定同位素评估
- 批准号:
8675270 - 财政年份:2013
- 资助金额:
$ 27.74万 - 项目类别:
Stable isotope evaluation of the methionine cycle in undernourished pregnancy
营养不良妊娠中蛋氨酸循环的稳定同位素评估
- 批准号:
8445720 - 财政年份:2013
- 资助金额:
$ 27.74万 - 项目类别:
Cortisol regulation of perinatal adipose tissue and sheep neonatal leptin peak
皮质醇对围产期脂肪组织和绵羊新生儿瘦素峰值的调节
- 批准号:
9258462 - 财政年份:2013
- 资助金额:
$ 27.74万 - 项目类别:
MATERNAL OBESITY IN PREGNANCY FETAL, PLACENTAL AND MATERNAL EFFECTS
孕期母亲肥胖对胎儿、胎盘和母体的影响
- 批准号:
8357676 - 财政年份:2011
- 资助金额:
$ 27.74万 - 项目类别:
NUTRIENT RESTRICTION-PLACENTAL AND FETAL BRAIN AND RENAL OUTCOMES AND MECHANISMS
营养限制——胎盘和胎儿的大脑和肾脏的结果和机制
- 批准号:
8357664 - 财政年份:2011
- 资助金额:
$ 27.74万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 27.74万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 27.74万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 27.74万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 27.74万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 27.74万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 27.74万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 27.74万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 27.74万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 27.74万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 27.74万 - 项目类别:
Research Grant