Dissecting connections between diet, the microbiome and Alzheimers disease
剖析饮食、微生物组和阿尔茨海默病之间的联系
基本信息
- 批准号:10740056
- 负责人:
- 金额:$ 25.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-15 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdvanced Glycosylation End ProductsAffectAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease patientAmericanAmerican dietAmino AcidsAmyloid beta-42Amyloid beta-ProteinAmyloid beta-Protein PrecursorAnimal DiseasesAnimalsBacteriaBrainBuffersCaenorhabditis elegansCirculationConsumptionDataDiabetes MellitusDietDietary SugarsEconomicsEnvironmentEscherichia coliFoodGenesGeneticGlucoseGoalsGrantHealthHealth Care CostsHumanImmuneImmune signalingIncidenceInflammationInterventionLinkLipidsLongevityMetabolismMicrobeMovementMuscleNeuronsOrthologous GeneOxidative StressParalysedPathogenicityPathway interactionsPeptidesPersonsPopulationProcessProteinsPublishingRegulationSeriesSeveritiesSignal PathwaySilverSourceStressStructureSystemTestingTissuesTransgenic AnimalsTransgenic OrganismsTsunamiabeta accumulationconstitutive expressiondietarygastrointestinal systemglycationgut microbiotahealthspaninducible gene expressioninsightmicrobiomemicrobiome alterationmicrobiotamutantpresenilinpromotersocial stressstress managementsugartool
项目摘要
Project Summary/Abstract
Our population is aging. As our population ages, the incidence of Alzheimer’s Disease (AD), an
age-associated illness, grows, resulting in elevated health care costs. A second factor contributing
to the current rise in age-associated aliments is the American diet with its ever-increasing amount
of added sugar. The negative effects of added dietary sugar is in part due to advanced glycation
end products (AGEs) which form from the process of glycation where a sugar molecule attaches
to a protein or lipid without enzymatic regulation thereby altering its structure and/or function.
AGEs form in normal metabolism but when AGEs rise to high levels in tissues and circulation, as
in diabetes or high dietary sugar, they can become pathogenic since AGEs promote oxidative
stress and inflammation. A third contributor to the increases in AD is the microbiome; recent
studies have linked age-associated illness with changes in the microbiome. The central unifying
hypothesis of this proposal is that consumption of a sugar-loaded diet alters the microbiome and
contributes to the onset and severity of AD. We will address this hypothesis with two specific aims
using a Caenorhabditis elegans–Escherichia coli system.
Our experimental C. elegans–E. coli paradigm is an excellent system for these studies
because: (1) C. elegans are bacterivores and have an obligatory symbiotic relationship with
microbes as their food source, which becomes the intestinal microbiota; (2) C. elegans possess
stress and immune signaling pathways that are evolutionarily conserved; (3) Genetic tools are
available including transgenic strains for AD whereby human β-Amyloid precursor protein (Aβ
peptide) is driven by a tissue specific promoter. (4) We can modify the environment (added sugar)
resulting in changes in the levels of dietary AGEs(dAGEs); and (5) Our preliminary data show
when C. elegans consume live (microbiota) or heat killed (no microbiota) sugar-loaded high-
dAGE E. coli, C. elegans have a shortened lifespan and reduced healthspan. Our results also
demonstrate the importance of the microbiota as a buffer for stress. In Specific Aim 1, we will
address the effects of a sugar-loaded high-dAGEs diet on AD transgenic animals with heat killed
or live bacteria. In Specific Aim 2, we use a series of genetic tools, (including mutants,
transgenics)to provide mechanistic insight. This proposal exploits a symbiotic relationship to
define how a sugar loaded/high dAGEs diet promotes Aβ accumulation. Our results in the two-
year period could be paradigm shifting in our understanding of the impact of added dietary glucose
on AD. The long-term goal is to modify diet to delay or even eliminate the onset of AD.
项目总结/文摘
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 }}
HEIDI A TISSENBAUM其他文献
HEIDI A TISSENBAUM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('HEIDI A TISSENBAUM', 18)}}的其他基金
Dissecting connections between age, health and Alzheimer's disease
剖析年龄、健康与阿尔茨海默病之间的联系
- 批准号:
10433227 - 财政年份:2020
- 资助金额:
$ 25.13万 - 项目类别:
Dissecting connections between age, health and Alzheimer's disease
剖析年龄、健康与阿尔茨海默病之间的联系
- 批准号:
10263907 - 财政年份:2020
- 资助金额:
$ 25.13万 - 项目类别:
Dissecting connections between age, health and Alzheimer's disease
剖析年龄、健康与阿尔茨海默病之间的联系
- 批准号:
10359290 - 财政年份:2020
- 资助金额:
$ 25.13万 - 项目类别:
Dissecting complex regulation by C. elegans DAF-16
解析秀丽隐杆线虫 DAF-16 的复杂调控
- 批准号:
7896672 - 财政年份:2009
- 资助金额:
$ 25.13万 - 项目类别:
Dissecting complex regulation by C. elegans DAF-16
解析秀丽隐杆线虫 DAF-16 的复杂调控
- 批准号:
7655731 - 财政年份:2009
- 资助金额:
$ 25.13万 - 项目类别:
Life span, Fat Storage and Insulin-like Signaling
寿命、脂肪储存和类胰岛素信号传导
- 批准号:
8729556 - 财政年份:2005
- 资助金额:
$ 25.13万 - 项目类别:
Life span, fat storage and insulin-like signaling
寿命、脂肪储存和胰岛素样信号传导
- 批准号:
7227419 - 财政年份:2005
- 资助金额:
$ 25.13万 - 项目类别:
Life span, fat storage and insulin-like signaling
寿命、脂肪储存和胰岛素样信号传导
- 批准号:
6903328 - 财政年份:2005
- 资助金额:
$ 25.13万 - 项目类别:
Life span, Fat Storage and Insulin-like Signaling
寿命、脂肪储存和类胰岛素信号传导
- 批准号:
8284360 - 财政年份:2005
- 资助金额:
$ 25.13万 - 项目类别:
Life span, Fat Storage and Insulin-like Signaling
寿命、脂肪储存和类胰岛素信号传导
- 批准号:
8101948 - 财政年份:2005
- 资助金额:
$ 25.13万 - 项目类别:
相似海外基金
ADVANCED GLYCOSYLATION END PRODUCTS AND EFFECT OF MESANGIAL CELLS
高级糖基化最终产物和对系膜细胞的影响
- 批准号:
3776700 - 财政年份:
- 资助金额:
$ 25.13万 - 项目类别:
ADVANCED GLYCOSYLATION END PRODUCTS AND EFFECT OF MESANGIAL CELLS
高级糖基化最终产物和对系膜细胞的影响
- 批准号:
3840306 - 财政年份:
- 资助金额:
$ 25.13万 - 项目类别:
ADVANCED GLYCOSYLATION END PRODUCTS AND EFFECT OF MESANGIAL CELLS
高级糖基化最终产物和对系膜细胞的影响
- 批准号:
3855332 - 财政年份:
- 资助金额:
$ 25.13万 - 项目类别:
GLOMERULAR EFFECTS OF ADVANCED GLYCOSYLATION END PRODUCTS
高级糖基化最终产物对肾小球的影响
- 批准号:
5202002 - 财政年份:
- 资助金额:
$ 25.13万 - 项目类别:
GLOMERULAR EFFECTS OF ADVANCED GLYCOSYLATION END PRODUCTS
高级糖基化最终产物对肾小球的影响
- 批准号:
3754540 - 财政年份:
- 资助金额:
$ 25.13万 - 项目类别: