Mapping Age-Related Changes in the Lung

绘制肺部与年龄相关的变化

基本信息

  • 批准号:
    10473606
  • 负责人:
  • 金额:
    $ 54.32万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-09-20 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

ABSTRACT Aging is associated with increased prevalence of lung diseases, such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and acute lung injury (ALI), however, the molecular mechanisms of the aging process that contribute to the pathogenesis of age-related lung diseases have not been completely elucidated. At a cellular level, only limited knowledge of the factors that define healthy aging of different lung cells is available. Based on the above, we propose to create an atlas of human aging lung (AHAL) consisting of transcriptomic maps of individual lung cell types. This will fill an existing knowledge gap and provide a rich resource for future research. Transcriptional differences might reflect genomic instability, alterations in stress responses and enrichment of markers of mitochondrial dysfunction, senescence and SASP. We also investigate the hypothesis that defective mitophagy is interconnected with senescence in the aging lung. Based on ours and other studies, we hypothesize that primary autocrine age-related senescence differs transcriptionally from the secondary paracrine senescence program observed in age-related lung diseases such as IPF We are proposing 3 independent aims to define age-related changes in the lung Aim 1: To map and characterize transcriptomic age-related changes in human lungs. We will perform single cell RNA sequence (scRNAseq) and bulk RNA sequence (RNAseq) from healthy young and aged human lungs and build a comprehensive atlas of transcriptomic changes in each lung cell type, as well as cell population shifts in aging lungs. In order to understand how chronological and functional ages differ, we will also compare the identified age-related gene signatures with those of the upper and lower lobe in IPF, an age- related lung disease. Data, results and lung cellular and transcriptome maps will be made publicly available through a cloud based comprehensive web portal that we will develop. Aim 2. To characterize the role of mitophagy in the aging lung and the senescence phenotype. We will investigate the hypotheses that augmenting mitophagy attenuates mitochondrial dysfunction in the aging lung and modulates the senescence phenotype. We have identified the mitochondrial deubiquitinase USP30, a negative regulator of mitophagy, as a key factor for mitophagy decline. As a proof of concept, we will investigate the potential pathogenic role of USP30 in the development of cell senescence using primary murine and human cells and USP30-/- mice. Aim 3. To identify senescence-related changes in aging lung cell compartments. We will examine how aging senescent cells and their SASP repertoire differ between cell compartments and contribute to tissue remodeling after injury. We will perform scRNAseq in isolated senescent cells from young and aged lungs and characterize their cell-specific senescent transcriptome. We will also investigate if age-related senescence is similar to senescence observed in cells from IPF lungs.!
摘要

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cellular Senescence in Lung Fibrosis.
  • DOI:
    10.3390/ijms22137012
  • 发表时间:
    2021-06-29
  • 期刊:
  • 影响因子:
    5.6
  • 作者:
    Hernandez-Gonzalez F;Faner R;Rojas M;Agustí A;Serrano M;Sellarés J
  • 通讯作者:
    Sellarés J
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PANAGIOTIS V BENOS其他文献

PANAGIOTIS V BENOS的其他文献

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{{ truncateString('PANAGIOTIS V BENOS', 18)}}的其他基金

COPD SUBTYPES AND EARLY PREDICTION USING INTEGRATIVE PROBABILISTIC GRAPHICAL MODELS R01HL157879
使用集成概率图形模型进行 COPD 亚型和早期预测 R01HL157879
  • 批准号:
    10705838
  • 财政年份:
    2022
  • 资助金额:
    $ 54.32万
  • 项目类别:
COPD SUBTYPES AND EARLY PREDICTION USING INTEGRATIVE PROBABILISTIC GRAPHICAL MODELS R01HL157879
使用集成概率图形模型进行 COPD 亚型和早期预测 R01HL157879
  • 批准号:
    10689580
  • 财政年份:
    2022
  • 资助金额:
    $ 54.32万
  • 项目类别:
Interpretable graphical models for large multi-modal COPD data (R01HL159805)
大型多模态 COPD 数据的可解释图形模型 (R01HL159805)
  • 批准号:
    10689574
  • 财政年份:
    2021
  • 资助金额:
    $ 54.32万
  • 项目类别:
COPD SUBTYPES AND EARLY PREDICTION USING INTEGRATIVE PROBABILISTIC GRAPHICAL MODELS
使用综合概率图模型进行慢性阻塞性肺病亚型和早期预测
  • 批准号:
    10206417
  • 财政年份:
    2021
  • 资助金额:
    $ 54.32万
  • 项目类别:
Interpretable graphical models for large multi-modal COPD data (R01HL159805)
大型多模态 COPD 数据的可解释图形模型 (R01HL159805)
  • 批准号:
    10705824
  • 财政年份:
    2021
  • 资助金额:
    $ 54.32万
  • 项目类别:
Mapping Age-Related Changes in the Lung
绘制肺部与年龄相关的变化
  • 批准号:
    10440882
  • 财政年份:
    2019
  • 资助金额:
    $ 54.32万
  • 项目类别:
Mapping Age-Related Changes in the Lung
绘制肺部与年龄相关的变化
  • 批准号:
    10020437
  • 财政年份:
    2019
  • 资助金额:
    $ 54.32万
  • 项目类别:
Systems Biology of Diffusion Impairment in HIV
HIV扩散损伤的系统生物学
  • 批准号:
    10188612
  • 财政年份:
    2018
  • 资助金额:
    $ 54.32万
  • 项目类别:
Systems Biology of Diffusion Impairment in HIV
HIV扩散损伤的系统生物学
  • 批准号:
    9753361
  • 财政年份:
    2018
  • 资助金额:
    $ 54.32万
  • 项目类别:
Systems Level Causal Discovery in Heterogeneous TOPMed Data
异构 TOPMed 数据中的系统级因果发现
  • 批准号:
    9310591
  • 财政年份:
    2017
  • 资助金额:
    $ 54.32万
  • 项目类别:

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