Vitamin D Metabolism and Lifespan Determination
维生素 D 代谢和寿命测定
基本信息
- 批准号:8919220
- 负责人:
- 金额:$ 23.52万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-01 至 2016-04-30
- 项目状态:已结题
- 来源:
- 关键词:25-hydroxyvitamin DAddressAdultAffectAgingAlzheimer&aposs DiseaseAmyloid beta-ProteinAmyloid depositionAnimal ModelAutophagocytosisBiological FactorsCaenorhabditis elegansCell Culture TechniquesChronicChronic DiseaseClinicalCommunitiesDataDevelopmentDiseaseDouble-blind trialElderlyEndoplasmic ReticulumEnzymesExploratory/Developmental GrantFutureGeneticGoalsHealthHealth BenefitHomeostasisHumanImpaired cognitionInfluentialsLaboratoriesLigandsLinkLongevityMalignant NeoplasmsMammalsMediatingMetabolicMetabolismMineralsMolecular ChaperonesNematodaNerve DegenerationNeurodegenerative DisordersNon-Insulin-Dependent Diabetes MellitusNuclearNuclear Hormone ReceptorsParkinson DiseasePathologyPathway interactionsPeptidesPharmaceutical PreparationsPhysiologic calcificationPhysiologicalPlayPopulationPropertyProteinsPublic HealthRiskRodent ModelRoleSignal TransductionSupplementationSystemTestingTo specifyTranslational ResearchTranslationsVitamin DVitamin D DeficiencyVitamin D3 ReceptorVitaminsWorkabeta accumulationage relatedboneclinical investigationinterestmouse modelnormal agingnovelprematurepreventprogramsreceptorresearch studyresponsesmall molecule libraries
项目摘要
DESCRIPTION (provided by applicant): Vitamin D has a critical role in bone mineral homeostasis but also has a broad range of other physiological effects. Deficiency of 25-hydroxyvitamin D, the major circulating form, is associated with increased risk of age-related chronic conditions including Alzheimer's disease, Parkinson's disease, cognitive impairment and a wide range of cancers. However, the mechanism that links vitamin D deficiency to diverse chronic diseases is unknown but it is suspected that elderly populations are vitamin D deficient. We have discovered that exposure of adult Caenorhabditis elegans (C. elegans) to D3 prevented the accumulation of a diverse range of insoluble proteins during aging and extended lifespan. It also prevents the aggregation of Abeta peptide. We have preliminary data that suggests that these beneficial effects require the endoplasmic reticulum unfolded protein response (ER UPR) and a nuclear hormone receptor (NHR-226) which may be acting as a vitamin D receptor. We aim to uncover the mechanism at play with a view to understanding the role played by vitamin D in human health. We propose to establish whether the effects of vitamin D are through a nuclear or a non-nuclear mechanism and establish how vitamin is affecting protein homeostasis. To do so, we must first understand vitamin D metabolism in C. elegans so we can manipulate vitamin D action. We expect our results could be influential how vitamin D is studied in relation to human chronic disease.
描述(由申请人提供):维生素D在骨矿物质稳态中具有关键作用,但也具有广泛的其他生理作用。缺乏25-羟基维生素D,主要的循环形式,与年龄相关的慢性疾病,包括阿尔茨海默病,帕金森病,认知障碍和各种癌症的风险增加有关。然而,维生素D缺乏症与各种慢性疾病之间的联系机制尚不清楚,但人们怀疑老年人缺乏维生素D。我们发现,暴露于秀丽隐杆线虫成虫(C。elegans)的D3阻止了各种不溶性蛋白质在衰老过程中的积累,延长了寿命。它还防止Abeta肽的聚集。我们有初步的数据表明,这些有益的作用需要内质网未折叠蛋白反应(ER UPR)和核激素受体(NHR-226),这可能是作为维生素D受体。我们的目标是揭示作用机制,以了解维生素D在人类健康中的作用。我们建议确定维生素D的作用是通过核机制还是非核机制,并确定维生素如何影响蛋白质稳态。要做到这一点,我们必须首先了解维生素D在C中的代谢。这样我们就可以控制维生素D的作用。我们希望我们的研究结果能够影响维生素D与人类慢性疾病的关系。
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)
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Gordon J Lithgow其他文献
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{{ truncateString('Gordon J Lithgow', 18)}}的其他基金
USC-Buck Institute Nathan Shock Admin Core
南加州大学巴克研究所 Nathan Shock 管理核心
- 批准号:
10044922 - 财政年份:2020
- 资助金额:
$ 23.52万 - 项目类别:
USC-Buck Institute Nathan Shock Admin Core
南加州大学巴克研究所 Nathan Shock 管理核心
- 批准号:
10649621 - 财政年份:2020
- 资助金额:
$ 23.52万 - 项目类别:
USC-Buck Institute Nathan Shock Admin Core
南加州大学巴克研究所 Nathan Shock 管理核心
- 批准号:
10424591 - 财政年份:2020
- 资助金额:
$ 23.52万 - 项目类别:
Targeting Aging to prevent Alzheimer's Disease: the Geroscience Approach
针对衰老预防阿尔茨海默病:老年科学方法
- 批准号:
10609412 - 财政年份:2020
- 资助金额:
$ 23.52万 - 项目类别:
Targeting Aging to prevent Alzheimer's Disease: the Geroscience Approach
针对衰老预防阿尔茨海默病:老年科学方法
- 批准号:
10385853 - 财政年份:2020
- 资助金额:
$ 23.52万 - 项目类别:
USC-Buck Institute Nathan Shock Admin Core
南加州大学巴克研究所 Nathan Shock 管理核心
- 批准号:
10261429 - 财政年份:2020
- 资助金额:
$ 23.52万 - 项目类别:
Caenorhabditis Intervention Testing Program - Data Coordination Center
秀丽隐杆线虫干预测试计划 - 数据协调中心
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9321578 - 财政年份:2017
- 资助金额:
$ 23.52万 - 项目类别:
Discovering compounds with robust pro-longevity activities
发现具有强大的长寿活性的化合物
- 批准号:
9117934 - 财政年份:2015
- 资助金额:
$ 23.52万 - 项目类别:
Vitamin D Metabolism and Lifespan Determination
维生素 D 代谢和寿命测定
- 批准号:
8769799 - 财政年份:2014
- 资助金额:
$ 23.52万 - 项目类别:
Caenorhabditis Intervention Testing Program - Buck Institute
秀丽隐杆线虫干预测试计划 - 巴克研究所
- 批准号:
10670432 - 财政年份:2013
- 资助金额:
$ 23.52万 - 项目类别:
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