Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins
衰老相关临床结果和Gero蛋白的综合评价
基本信息
- 批准号:9519838
- 负责人:
- 金额:$ 63.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-06-01 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:ART proteinAdultAdverse effectsAgeAgingAnemiaAtherosclerosisBaltimoreBiological AssayBiologyBiometryBlood VesselsBody CompositionBrainCCL11 geneCardiologyCardiovascular DiseasesCause of DeathCessation of lifeClinicalCognitionCognitiveColon CarcinomaCommunitiesCoronary heart diseaseDataDementiaDiagnosisEFRACElderlyEnzyme-Linked Immunosorbent AssayEpidemiologic MethodsErythropoiesisEvaluationExhibitsFSTL3 geneFamilyFollistatinGDF11 geneGDF8 geneGeneral PopulationGeriatricsGoalsGrowth and Development functionHealthHeart HypertrophyHeart failureHomologous GeneHormonesHospitalizationHumanImmunoassayImpaired cognitionInflammatory ResponseInjuryInvestigationLaboratoriesLeft Ventricular MassLongevityLongitudinal StudiesMalignant NeoplasmsMass Spectrum AnalysisMeasuresMemoryMusMuscleMyocardiumNatural regenerationNeurologyOutcomeOxytocinParabiosisPathway interactionsPatternPeptidesPhenotypePhysiologicalPlayProteinsProteomicsProtocols documentationRaceReportingResearch PersonnelRiskRoleScienceSkeletal MuscleSmell PerceptionSpecific qualifier valueSpecificitySpecimenTestingTissuesTransforming Growth Factor betaTranslatingVariantadverse outcomeage relatedaptamerbasebeta-2 Microglobulinbiracialcardiovascular disorder riskcardiovascular healthclinical phenotypecognitive functioncohortdisabilityeffective therapyexperimental studyfollow-uphemodynamicsimprovedinnovationliquid chromatography mass spectrometrymembermortalitymuscle strengthneurogenesisnew therapeutic targetpopulation basedpsychologicpublic health relevancereproductivesexyoung adult
项目摘要
DESCRIPTION (provided by applicant): We propose to test whether mouse experiments showing that circulating proteins can rejuvenate or accelerate aging in the brain, heart, and skeletal muscle translate into corresponding associations with important clinical outcomes in older adults. Using an assay for GDF11 that has since been determined also to measure its close structural homologue, GDF8, we demonstrated in preliminary studies that these geronic proteins are associated with incident heart failure (HF) and atherosclerotic cardiovascular disease (ASCVD) in cohorts with prevalent coronary disease. By contrast, follistatin-like 3, an antagonist of GDF11 and GDF8, exhibited the opposite associations. These findings highlight the need to identify more specific assays, and they also call for broader investigation of relevant
pathways in general population-based cohorts. We will therefore undertake systematic comparisons of state-of-the-art LC mass spectroscopy, aptamer-based proteomics, and immunoassays to select the best assay for each protein. We will then harness the comprehensive clinical phenotyping and exceptional statistical power of two large, biracial cohorts, the Cardiovascular Health Study and the Health Aging, and Body Composition Study to efficiently test the following hypotheses. First, that higher levels of CCL11 and of ß2 microglobulin, which decrease neurogenesis in mice, are associated with impaired cognitive function and increased risk of dementia. Second, that as in mice, higher levels of GDF11 are associated with lower left ventricular (LV) mass and reduced risk of heart failure, particularly with preserved ejection fraction (HFpEF), ASCVD, and risk of dementia. Third, that higher levels of GDF11 and oxytocin are associated with improved skeletal muscle strength and reduced risk of mobility disability. Beyond these endpoints, we will also examine various adverse outcomes. Moreover, we will describe how levels of these proteins vary across the lifespan, from age 20 to 96, using data and specimens from the Baltimore Longitudinal Study of Aging. These data will enable us to analyze how levels of these proteins influence cognition, LV mass, and muscle strength across the life span. The proposed study will be led by a coordinated team of PIs and investigators who are leaders in their fields of laboratory science, geriatrics, cardiology, neurology, muscle and mobility, and biostatistics. An exceptional Scientific Advisory board of leaders in parabiosis and the basic biology of these proteins has and will continue to inform our choices of peptides and phenotypes, and guide analyses of our data. Hence, the proposed study will provide a comprehensive analysis of these exciting proteins in human cohorts with the aim of identifying novel therapeutic targets for major causes of disability and mortality for which
few effective treatments are currently available.
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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STEVEN RON CUMMINGS其他文献
STEVEN RON CUMMINGS的其他文献
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{{ truncateString('STEVEN RON CUMMINGS', 18)}}的其他基金
Study of Muscle, Mobility and Aging (SOMMA)
肌肉、活动能力和衰老研究 (SOMMA)
- 批准号:
10170192 - 财政年份:2018
- 资助金额:
$ 63.5万 - 项目类别:
Prevention of Fractures in Patients with Parkinson's Disease
帕金森病患者骨折的预防
- 批准号:
10617169 - 财政年份:2018
- 资助金额:
$ 63.5万 - 项目类别:
Study of Muscle, Mobility and Aging: SOMMA2
肌肉、活动能力和衰老研究:SOMMA2
- 批准号:
10913728 - 财政年份:2018
- 资助金额:
$ 63.5万 - 项目类别:
Study of Muscle, Mobility and Aging (SOMMA)
肌肉、活动能力和衰老研究 (SOMMA)
- 批准号:
10441623 - 财政年份:2018
- 资助金额:
$ 63.5万 - 项目类别:
Study of Muscle, Mobility and Aging (SOMMA)
肌肉、活动能力和衰老研究 (SOMMA)
- 批准号:
10015194 - 财政年份:2018
- 资助金额:
$ 63.5万 - 项目类别:
Study of Muscle, Mobility and Aging (SOMMA)
肌肉、活动能力和衰老研究 (SOMMA)
- 批准号:
10652212 - 财政年份:2018
- 资助金额:
$ 63.5万 - 项目类别:
Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins
衰老相关临床结果和Gero蛋白的综合评价
- 批准号:
9279037 - 财政年份:2016
- 资助金额:
$ 63.5万 - 项目类别:
Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins - SUPPLEMENT
衰老相关临床结果和老年蛋白的综合评估 - 补充材料
- 批准号:
9445352 - 财政年份:2016
- 资助金额:
$ 63.5万 - 项目类别:
Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins
衰老相关临床结果和Gero蛋白的综合评价
- 批准号:
9119555 - 财政年份:2016
- 资助金额:
$ 63.5万 - 项目类别:
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