Genetic variant-based drug discovery targeting conserved pathways of aging
针对保守的衰老途径的基于遗传变异的药物发现
基本信息
- 批准号:9359668
- 负责人:
- 金额:$ 191.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-15 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAgingAnimal ModelApoptosisBiological AssayCardiovascular DiseasesCell AgingCell Culture SystemCellsCentenarianClinicalCodeCollaborationsComputer SimulationDevelopmentDiseaseDrug TargetingElderlyFDA approvedFRAP1 geneFVB MouseFamily history ofFoundationsGene ExpressionGene TargetingGenesGeneticGenetic VariationGenetically Engineered MouseGenome engineeringGenomic InstabilityGenotypeHealthHumanHuman EngineeringHuman GeneticsHybridsI Kappa B-AlphaIGF1 geneIndividualInterventionLinkLongevityLongevity PathwayMalignant NeoplasmsMedicineMicroRNAsModelingMolecularMusMutagensNatural ProductsNatureNerve DegenerationNon-Insulin-Dependent Diabetes MellitusNucleic Acid Regulatory SequencesOutcomePathologicPathway interactionsPharmaceutical PreparationsPharmacologic SubstancePharmacologyPhenotypePhysiological ProcessesPlaguePopulationRegulationResearchResearch Project GrantsResourcesRisk FactorsSignal TransductionSymptomsTestingTherapeuticUntranslated RNAVariantage relatedagedbasecollegedrug discoveryefficacy testingexomeexperimental studyfollower of religion Jewishgenetic resourcegenetic varianthealthy aginghuman diseasemiddle agemouse modelmutantnovelnovel strategiesnovel therapeuticspreventrare variantresponsescreeningsmall moleculesmall molecule inhibitortherapeutic developmenttherapy developmenttoolwardwhole genome
项目摘要
ABSTRACT - OVERALL
Aging is an important risk factor for most common human diseases, including type 2 diabetes, cardiovascular
disease, cancer and neurodegeneration. In the proposed collaborative U19 proposal, we will test a new
approach for developing therapies for these diseases. Rather than focusing on individual diseases, we will
explore genetic differences between successfully aged, healthy centenarians and control individuals with no
family history of extreme longevity. Based on our own preliminary results, many of such genetic differences
affect loci known to be involved in extreme longevity and health span in model organisms, such as worms and
mice. Using the centenarian resource at the Albert Einstein College of Medicine, we will identify rare genetic
variants and microRNAs associated with conserved mechanisms of healthy longevity as potential targets, for
drug discovery (Project 1), evaluate these variants or associated pathways functionally in mouse models of
aging, including natural aging, for phenotypes relevant for late-life human health (Project 2), and subsequently
use them as leads for developing and testing small molecules targeting the pathways affected by these rare
variants and miRNAs (Project 3). This integrated research project will be supported by two cores: an
Administrative Core to coordinate the research (Core A) and a Genetically Engineered Mouse and
Geropathology Core (Core B). Using our extensive genetic resources, including some from our pharmaceutical
partner, Regeneron, we also will confirm further and validate some of the genetic variants and discover
additional, novel genetic variants and associated pathways important for human longevity. The proposed
project should greatly increase our understanding of the importance of the conserved pro-longevity pathways,
identified and thus far mostly studied in model organisms, for human aging. Importantly, this gene to drugs
collaborative project will be the first to use the genetics of rare individuals with healthy aging as a guide for the
development of therapeutic approaches for targeting aging itself rather than its composite diseases for
preventing, delaying onset and progression, and possibly even reverting many multiple age-related diseases.
摘要-总体
项目成果
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{{ truncateString('JAN VIJG', 18)}}的其他基金
Development of novel therapeutics targeting the identified pathways associated with human longevity
针对已确定的与人类长寿相关的途径开发新疗法
- 批准号:
10714394 - 财政年份:2017
- 资助金额:
$ 191.07万 - 项目类别:
Genetic variant-based drug discovery targeting conserved pathways of aging
针对保守的衰老途径的基于遗传变异的药物发现
- 批准号:
9916672 - 财政年份:2017
- 资助金额:
$ 191.07万 - 项目类别:
Validation and characterization of the identified variants associated with human longevity in mouse models
在小鼠模型中验证和表征与人类长寿相关的已识别变异
- 批准号:
10714393 - 财政年份:2017
- 资助金额:
$ 191.07万 - 项目类别:
Identification and characterization of functional genetic variants associated with human longevity
与人类长寿相关的功能性遗传变异的鉴定和表征
- 批准号:
10714392 - 财政年份:2017
- 资助金额:
$ 191.07万 - 项目类别:
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