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

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)
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会议论文数量(0)
专利数量(0)

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Nathan K LeBrasseur其他文献

Nathan K LeBrasseur的其他文献

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{{ truncateString('Nathan K LeBrasseur', 18)}}的其他基金

Biological Analysis Core
生物分析核心
  • 批准号:
    10552988
  • 财政年份:
    2022
  • 资助金额:
    $ 56.83万
  • 项目类别:
Biological Analysis Core
生物分析核心
  • 批准号:
    10675012
  • 财政年份:
    2022
  • 资助金额:
    $ 56.83万
  • 项目类别:
Skeletal Muscle Loss and Dysfunction
骨骼肌损失和功能障碍
  • 批准号:
    10561633
  • 财政年份:
    2019
  • 资助金额:
    $ 56.83万
  • 项目类别:
Skeletal Muscle Loss and Dysfunction
骨骼肌损失和功能障碍
  • 批准号:
    10349488
  • 财政年份:
    2019
  • 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:
    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:

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