Senescence and Growth Differentiation Factors as Modifiers of Aging
衰老和生长分化因子作为衰老调节剂
基本信息
- 批准号:10116228
- 负责人:
- 金额:$ 56.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-15 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAgingAmino Acid SequenceAntibodiesArteriesBasic ScienceBiologicalBiological AgingBiological AssayBiological MarkersBlood PressureBlood specimenBody CompositionCCL11 geneCardiopulmonaryCardiovascular systemCell Adhesion MoleculesCell AgingCellsChronicChronic DiseaseClinicalCodeCognitiveCohort StudiesCollaborationsDataDifferentiation and GrowthDiseaseDrug TargetingElderlyEotaxinEventExcisionForced expiratory volume functionGDF11 geneGDF8 geneGait speedGeroscienceGrowth FactorHealthHealth StatusHealth educationHeart failureHumanICD-9ImpairmentIncidenceInflammationInnovative TherapyInterventionLiquid ChromatographyLongevityLow PrevalenceMeasuresMediatingMediator of activation proteinMemoryMethodsMusMuscleMyocardial InfarctionOutcomeParticipantPartner in relationshipPhenotypePhysical FunctionPhysical PerformancePhysical activityPlasmaPlasminogen Activator Inhibitor 2Pre-Clinical ModelPrevalenceProteinsRejuvenationResearchRisk FactorsSamplingSensitivity and SpecificityStrokeStructureTestingTherapeutic InterventionTime StudyTranslationsVascular remodelingWalkingWorkactivin Aadjudicateage relatedanalytical methodbasecognitive functiondisabilityevidence baseexercise interventionfall injuryfallshealthspaninnovationlifestyle interventionmorphogensmultidisciplinarymultiple chronic conditionsneurogenesisnovelolder menolder womenpreventprocessing speedprogramsrandomized trialregeneration potentialregenerative tissuesenescencetandem mass spectrometrytissue regeneration
项目摘要
PROJECT SUMMARY/ABSTRACT
Aging is the primary risk factor for the majority of chronic diseases. Studies in mice have implicated specific
growth and differentiation factors (GDFs) and proteins secreted by senescent cells as potential modifiers of
aging. The objective of this proposal is to establish the rationale and provide robust clinical evidence for GDF8,
GDF11, and senescence-related proteins eotaxin (CCL11), intracellular adhesion molecule 1 (ICAM1), activin
A (AA), and plasminogen activator inhibitor 2 (PAI2), as indicators of biological age and age-related conditions
in humans. The central hypothesis is that circulating concentrations of GDFs and senescence-related proteins
are associated with, and predictive of, clinically important health outcomes and can be altered by physical
activity. Samples from the Lifestyle Interventions and Independence for Elders (LIFE) Study; the largest and
longest randomized trial of a physical activity intervention in older adults, will be used to test this hypothesis,
and samples from the Health, Aging, and Body Composition (HABC) Study will be used to validate study
findings. A novel multiplexed liquid chromatography-tandem mass spectrometry assay will be leveraged to
accurately quantify GDFs, and an advanced multiplexing platform will be used to measure senescence-related
proteins in LIFE and HABC biospecimens. In Specific Aim 1, a multidisciplinary team will first determine the
extent to which baseline concentrations of GDF8, GDF11, CCL11, ICAM1, AA and PAI2 are associated with
baseline measures of physical (i.e., gait speed, Short Physical Performance Battery (SPPB) score),
cardiopulmonary (i.e., blood pressure, forced expiratory volume), and cognitive (i.e., processing speed,
memory) function, inflammation, and prevalence of multimorbidity (based on the ICD-9 codes for 20 chronic
conditions). In Specific Aim 2, the degree to which baseline concentrations of GDFs and senescence-related
proteins predict longitudinal changes in a) gait speed and SPPB score, b) major mobility disability (i.e., the
inability to walk 400m), c) combined cardiovascular events (e.g., myocardial infarction, heart failure, stroke); d)
adjudicated falls and injurious falls, e) cognitive function (as Aim 1), and f) the number of chronic conditions (as
in Aim 1), at 1 and 2 years in LIFE and at 2 and 4 years in HABC will be determined. Finally, Specific Aim 3 will
address whether a structured physical activity intervention impacts longitudinal changes in GDF8, GDF11,
CCL11, ICAM1, AA, and PAI2, compared to a health education control intervention, and the degree to which
change in the concentrations of these proteins parallel change in the health outcomes described in Aim 2. The
successful completion of the proposed research will fill an important translational gap in our understanding of
how GDFs and senescence-related proteins predict and, therefore, potentially mediate aging related disability
and disease in older women and men. Ultimately, these proteins may be viable targets for innovative therapies
to extend human healthspan.
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 }}
Nathan K LeBrasseur其他文献
Nathan K LeBrasseur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('Nathan K LeBrasseur', 18)}}的其他基金
Senescence and Growth Differentiation Factors as Modifiers of Aging
衰老和生长分化因子作为衰老调节剂
- 批准号:
9755279 - 财政年份:2018
- 资助金额:
$ 56.83万 - 项目类别:
Senescence and Growth Differentiation Factors as Modifiers of Aging
衰老和生长分化因子作为衰老调节剂
- 批准号:
10378047 - 财政年份:2018
- 资助金额:
$ 56.83万 - 项目类别:
Interdisciplinary Infrastructure for Aging Research: Rochester Epidemiology Project
老龄化研究的跨学科基础设施:罗切斯特流行病学项目
- 批准号:
10208373 - 财政年份:2018
- 资助金额:
$ 56.83万 - 项目类别:
Interdisciplinary Infrastructure for Aging Research: Rochester Epidemiology Project
老龄化研究的跨学科基础设施:罗切斯特流行病学项目
- 批准号:
10409783 - 财政年份:2018
- 资助金额:
$ 56.83万 - 项目类别:
Senescence and Growth Differentiation Factors as Modifiers of Aging
衰老和生长分化因子作为衰老调节剂
- 批准号:
9894701 - 财政年份:2018
- 资助金额:
$ 56.83万 - 项目类别:
Interdisciplinary Infrastructure for Aging Research: Rochester Epidemiology Project
老龄化研究的跨学科基础设施:罗切斯特流行病学项目
- 批准号:
10224079 - 财政年份:2018
- 资助金额:
$ 56.83万 - 项目类别:
相似海外基金
Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
- 批准号:
495182 - 财政年份:2023
- 资助金额:
$ 56.83万 - 项目类别:
Parkinson's disease and aging affect neural activation during continuous gait alterations to the split-belt treadmill: An [18F] FDG PET Study.
帕金森病和衰老会影响分体带跑步机连续步态改变期间的神经激活:[18F] FDG PET 研究。
- 批准号:
400097 - 财政年份:2019
- 资助金额:
$ 56.83万 - 项目类别:
The elucidation of the mechanism by which intestinal epithelial cells affect impaired glucose tolerance during aging
阐明衰老过程中肠上皮细胞影响糖耐量受损的机制
- 批准号:
19K09017 - 财政年份:2019
- 资助金额:
$ 56.83万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Does aging of osteocytes adversely affect bone metabolism?
骨细胞老化会对骨代谢产生不利影响吗?
- 批准号:
18K09531 - 财政年份:2018
- 资助金额:
$ 56.83万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Links between affect, executive function, and prefrontal structure in aging: A longitudinal analysis
衰老过程中情感、执行功能和前额叶结构之间的联系:纵向分析
- 批准号:
9766994 - 财政年份:2018
- 资助金额:
$ 56.83万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9320090 - 财政年份:2017
- 资助金额:
$ 56.83万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
10166936 - 财政年份:2017
- 资助金额:
$ 56.83万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9761593 - 财政年份:2017
- 资助金额:
$ 56.83万 - 项目类别:
Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
衰老过程中抑郁症的实验模型:失眠、炎症和影响机制
- 批准号:
9925164 - 财政年份:2016
- 资助金额:
$ 56.83万 - 项目类别:
Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
衰老过程中抑郁症的实验模型:失眠、炎症和影响机制
- 批准号:
9345997 - 财政年份:2016
- 资助金额:
$ 56.83万 - 项目类别: