Validation and optimization of epigenetic clocks
Validation and optimization of epigenetic clocks
批准号:
10171750
负责人:
Beate R Ritz
金额:
$55.81万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-30 至 2023-05-31
关键词:
AddressAgeAgingBiologicalBiological AssayBiological MarkersBloodBlood Cell CountCDKN2A geneCell AgingCellsCentenarianClinical ResearchClinical TrialsCohort StudiesCollectionDNA MethylationDataEffectiveness of InterventionsEndothelial CellsEpigenetic ProcessFibroblastsGeneticGenetic TranscriptionGenetic studyGlucoseGoalsGrantHealthHumanInterventionIntervention StudiesInvestigationLeadLengthLeukocytesLipidsLiquid substanceLongevityLongitudinal StudiesLongitudinal cohort studyMeasuresMendelian randomizationMethylationMolecularMolecular TargetOutcomePhaseProcessProteomicsProtocols documentationResearchResearch PersonnelSalivaSamplingStandardizationSystemT-LymphocyteTestingTissue SampleUrineValidationVariantWorkage relatedanti agingbasebiomarker panelclinical applicationclinical biomarkerscohortdesigneffectiveness testinghealthspanhigh-throughput drug screeninginflammatory markerinsightkeratinocytelifestyle interventionmetabolomicsmethylation biomarkermolecular markermultiple chronic conditionsnovelpredictive markerprogramsprototypesenescencetelomeretranscriptomics
中文摘要
项目概要/摘要
寻找和验证延长人类健康寿命的分子靶点一直具有挑战性,因为大多数人都认为,
临床生物标志物既不充分机械,也不接近老化的基本机制,
作为指标。为了应对开发衰老生物标志物的挑战,我们将主要关注
表观遗传改变,因为它是非常有可能的,与这项工作的DNA甲基化(DNA)将出来,作为一个
有效的生物标志物准备用于临床应用。该提案的总体目标是:(a)实现
基于DNAm的衰老生物标志物(称为表观遗传时钟)有望用于人类干预研究
和B)推进他们的机械理解。这项建议建立在我们积极的研究计划之上
周围的基于DNAm的衰老生物标志物及其与细胞衰老标志物的关系。我们
和其他人已经证明,现有的DNAm生物标志物原型可以预测寿命,
许多与年龄有关的问题。我们已经确定,一些DNAm生物标志物与生活方式干预有关,
现有的DNAm生物标志物已经被用于抗衰老干预的人体临床试验。与
这些概念验证研究完成后,我们进入了下一个阶段,这些生物标志物需要
优化以跟踪人类研究中干预措施的有效性。尽管人们普遍认为,
DNAm生物标志物非常稳健,它们对技术变化保持敏感。尽量减少这种
虚假的变化,我们将优化工作流程中的所有组件,从人类样本的收集到
分析的最后一点。
在我们之前的计划拨款中,我们的研究人员网络设计了一项研究,用于评估DNAm的效用。
基于人类纵向队列研究中的衰老生物标志物。根据这些计划,我们将测试
DNAm生物标志物是通过进行人类健康评估的基础衰老过程的指标。
纵向队列研究、遗传学研究和干预性研究。我们将把DNA生物标志物与
细胞衰老的标志物和一系列衰老的临床生物标志物,以推进衰老的机制。
见解.我们将评估一组生物标志物是否更能预测健康span/多种健康
而不是一个单一的标志。我们将优化DNAm生物标志物用于人体离体研究
用于测试对各种抗衰老或促衰老干预的反应性。所得到的优化系统还
作为一个潜在的高通量药物筛选系统,它将具有可控的优势,
潜在的混杂因素,并且是人源性的。总的来说,这些调查将导致(a)
在人类介入治疗中应用DNAm生物标志物的整个工作流程的优化
研究和(B)充分描述每种生物标志物的目的和用途的使用背景声明。
英文摘要
Project Summary/Abstract
It has been challenging to find and validate molecular targets for extending human healthspan because most
clinical biomarkers are neither sufficiently mechanistic nor proximal to fundamental mechanisms of aging to
serve as indicators. To address the challenge of developing biomarkers of aging, we will primarily focus on
epigenetic alterations because it is highly likely that with this work DNA methylation (DNA) will come out as a
valid biomarker ready for clinical application. The overarching goals of this proposal are a) to realize the great
promise of DNAm based biomarkers of aging (known as epigenetic clocks) for human interventional studies
and b) to advance their mechanistic understanding. This proposal builds on our active research program
surrounding DNAm based biomarkers of aging and their relationship to markers of cellular senescence. We
and others have demonstrated that existing prototypes of DNAm biomarkers are predictive of lifespan and
many age-related conditions. We have established that some DNAm biomarkers relate to lifestyle interventions
and existing DNAm biomarkers are already being used in human clinical trials of anti-aging interventions. With
these proof-of-concept studies completed, we enter the next phase where these biomarkers need to be
optimized to track the effectiveness of interventions in human studies. Although it is widely acknowledged that
DNAm biomarkers are remarkably robust, they remain sensitive to technical variation. To minimize such
spurious variation, we will optimize all components within the workflow, from collection of human samples to
the final point of analysis.
In our previous planning grant, our network of researchers designed a study for evaluating the utility of DNAm
based biomarkers of aging in human longitudinal cohort studies. Building on these plans, we will test whether
DNAm biomarkers are indicators of a fundamental aging process underlying healthspan by carrying out human
longitudinal cohort studies, genetic studies, and interventional studies. We will relate DNAm biomarkers to
markers of cellular senescence and a battery of clinical biomarkers of aging in order to advance mechanistic
insights. We will evaluate whether a panel of biomarkers is more predictive of healthspan/multiple health
outcomes as opposed to a single marker. We will optimize DNAm biomarkers for use in human ex vivo studies
for testing responsiveness to various anti-aging or pro-aging interventions. The resulting optimized system also
serves as a potential high-throughput drug screening system, which will have the advantage of being controlled
for potential confounding factors and is of human origin. Collectively, these investigations will result in (a) the
optimization of the entire workflow process for the application of DNAm biomarkers in human interventional
studies and (b) context-of-use statements that fully describe the purpose and use of each biomarker.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Air Pollution, Metabolome, and Alzheimer disease in Mexican Americans
-
批准号:10591306
-
项目类别:
-
资助金额:$227.44万
-
财政年份:2022
-
负责人:Beate R Ritz
-
依托单位:
A Multi-omics approach to Environment and Depression in Parkinsons disease (MOOD-PD)
-
批准号:10493187
-
项目类别:
-
资助金额:$19.5万
-
财政年份:2021
-
负责人:Beate R Ritz
-
依托单位:
A Multi-omics approach to Environment and Depression in Parkinsons disease (MOOD-PD)
-
批准号:10304018
-
项目类别:
-
资助金额:$23.4万
-
财政年份:2021
-
负责人:Beate R Ritz
-
依托单位:
Microbiome, Environment, and Parkinsons disease (MEP) PESTICIDE EXPOSURES AND THE GUT MICROBIOME IN PARKINSONS DISEASE
-
批准号:10436325
-
项目类别:
-
资助金额:$63.35万
-
财政年份:2020
-
负责人:Beate R Ritz
-
依托单位:
Microbiome, Environment, and Parkinsons disease (MEP) PESTICIDE EXPOSURES AND THE GUT MICROBIOME IN PARKINSONS DISEASE
-
批准号:10872374
-
项目类别:
-
资助金额:$14.82万
-
财政年份:2020
-
负责人:Beate R Ritz
-
依托单位:
Microbiome, Environment, and Parkinsons disease (MEP) PESTICIDE EXPOSURES AND THE GUT MICROBIOME IN PARKINSONS DISEASE
-
批准号:10652545
-
项目类别:
-
资助金额:$62.6万
-
财政年份:2020
-
负责人:Beate R Ritz
-
依托单位:
Microbiome, Environment, and Parkinsons disease (MEP) PESTICIDE EXPOSURES AND THE GUT MICROBIOME IN PARKINSONS DISEASE
-
批准号:10053242
-
项目类别:
-
资助金额:$66.16万
-
财政年份:2020
-
负责人:Beate R Ritz
-
依托单位:
Microbiome, Environment, and Parkinsons disease (MEP) PESTICIDE EXPOSURES AND THE GUT MICROBIOME IN PARKINSONS DISEASE
-
批准号:10641067
-
项目类别:
-
资助金额:$14.82万
-
财政年份:2020
-
负责人:Beate R Ritz
-
依托单位:
Microbiome, Pesticides and Parkinsons in Latinos
-
批准号:10415745
-
项目类别:
-
资助金额:$14.82万
-
财政年份:2020
-
负责人:Beate R Ritz
-
依托单位:
Microbiome, Environment, and Parkinsons disease (MEP) PESTICIDE EXPOSURES AND THE GUT MICROBIOME IN PARKINSONS DISEASE
-
批准号:10240329
-
项目类别:
-
资助金额:$65.18万
-
财政年份:2020
-
负责人:Beate R Ritz
-
依托单位:
Validation and optimization of epigenetic clocks
-
批准号:10413103
-
项目类别:
-
资助金额:$55.5万
-
财政年份:2018
-
负责人:Beate R Ritz
-
依托单位:
Childhood Autism and Air Pollution - A Statewide Study
-
批准号:8917748
-
项目类别:
-
资助金额:$20.62万
-
财政年份:2015
-
负责人:Beate R Ritz
-
依托单位:
Pesticide Exposure and Cerebral Palsy
-
批准号:8954475
-
项目类别:
-
资助金额:$7.7万
-
财政年份:2015
-
负责人:Beate R Ritz
-
依托单位:
Psychosocial stressors, air pollution and childhood respiratory health in LAFANS
-
批准号:9115185
-
项目类别:
-
资助金额:$6.88万
-
财政年份:2015
-
负责人:Beate R Ritz
-
依托单位:
Pesticide Exposure and Cerebral Palsy
-
批准号:9114604
-
项目类别:
-
资助金额:$7.7万
-
财政年份:2015
-
负责人:Beate R Ritz
-
依托单位:
Air Pollution and Autism in Denmark
-
批准号:9115167
-
项目类别:
-
资助金额:$16.64万
-
财政年份:2015
-
负责人:Beate R Ritz
-
依托单位:
Autism Metabolomics and Environment (AIME)
-
批准号:8917749
-
项目类别:
-
资助金额:$24.42万
-
财政年份:2015
-
负责人:Beate R Ritz
-
依托单位:
Air Pollution and Autism in Denmark
-
批准号:8891906
-
项目类别:
-
资助金额:$19.52万
-
财政年份:2015
-
负责人:Beate R Ritz
-
依托单位:
Childhood Autism and Air Pollution - A Statewide Study
-
批准号:9116172
-
项目类别:
-
资助金额:$23.1万
-
财政年份:2015
-
负责人:Beate R Ritz
-
依托单位:
2013 Environment & Health Joint Conference of the ISEE, ISE, and ISIAQ
-
批准号:8652021
-
项目类别:
-
资助金额:$2.2万
-
财政年份:2013
-
负责人:Beate R Ritz
-
依托单位:
国内基金
海外基金
登录
查看更多内容
补阳还五汤通过AGE-RAGE通路调控脓毒症免疫失衡的机制与转化研究
-
批准号:JCZRLH202601523
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:
-
依托单位:
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
-
批准号:JCZRQN202500010
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:
-
依托单位:
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
-
批准号:2025JJ70209
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:雷芬芳
-
依托单位:
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
-
批准号:--
-
项目类别:面上项目
-
资助金额:--
-
批准年份:2024
-
负责人:万荣
-
依托单位:
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
-
批准号:2023JJ50274
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2023
-
负责人:贺志明
-
依托单位:
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
-
批准号:--
-
项目类别:地区科学基金项目
-
资助金额:33万元
-
批准年份:2022
-
负责人:都义日
-
依托单位:
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
-
批准号:--
-
项目类别:面上项目
-
资助金额:52万元
-
批准年份:2022
-
负责人:叶宝东
-
依托单位:
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:10.0万元
-
批准年份:2022
-
负责人:于海兵
-
依托单位:
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
-
批准号:81973577
-
项目类别:面上项目
-
资助金额:55.0万元
-
批准年份:2019
-
负责人:辛贵忠
-
依托单位:
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
-
批准号:81602908
-
项目类别:青年科学基金项目
-
资助金额:18.0万元
-
批准年份:2016
-
负责人:刘括
-
依托单位: