Age-related vascular cognitive impairment: role of endothelial senescence

年龄相关的血管认知障碍:内皮衰老的作用

基本信息

  • 批准号:
    10044293
  • 负责人:
  • 金额:
    $ 36.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-01 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ ABSTRACT More than 50 million people over the age of 65 are currently affected by vascular cognitive impairment and dementia (VCID). Although the specific mechanisms for aging- induced VCID are not yet known, there is increasing evidence that alterations of the neurovascular unit play a crucial role. The objective of this proposal is to elucidate the mechanistic role of senescence-related endothelial dysfunction in cognitive impairment. The central hypothesis is that aging primarily promotes endothelial senescence in the brain and subsequent dysfunction, altering the production of vasodilator mediators, impairing neurovascular coupling responses, promoting blood-brain barrier (BBB) disruption and microvascular rarefaction. The resulting decline in cerebral blood flow (CBF) and increased neuroinflammation contribute to cognitive impairment. The proposed work is novel as it will be the first to demonstrate that aging-induced endothelial senescence is a critical contributing factor to the pathogenesis of VCID. The results will likely identify specific mechanisms and reveal potential therapies that are capable of improving CBF and restoring learning and memory. The following aims are proposed: 1) Determine how endothelial senescence alters neurovascular coupling responses, CBF and cognition in aging. The working hypothesis is that aging-induced activation of p16-dependent cellular senescence program in endothelial cells impairs vasodilator function. It is predicted that elimination of senescent endothelial cells, through genetic manipulation or through senolytic therapies will restore neurovascular function and improve CBF and cognition in aged mice. 2) Determine how senescence alters microvascular density and BBB integrity in aging. The working hypothesis is that activation of p16-dependent cellular senescence program in endothelial cells impairs endothelial barrier function and compromise the maintenance of the microcirculatory network. It is predicted that elimination of senescent cells will restore BBB, attenuating neuroinflammation and increase cerebromicrovascular density in aged mice. 3) Determine cellular heterogeneity among senescent endothelial cells in conjunction with their morphological and functional characteristics. Together, the proposed studies will identify a fundamental mechanism governing aging-induced cerebrovascular changes eventually leading to cognitive impairment.
项目总结/摘要 超过5000万65岁以上的人目前受到血管疾病的影响。 认知障碍和痴呆(VCID)。尽管衰老的具体机制- 诱导的VCID尚不清楚,但越来越多的证据表明, 神经血管单位起关键作用。本提案的目的是阐明 衰老相关内皮功能障碍在认知功能障碍中的机制作用的 中心假设是衰老主要促进脑中的内皮衰老, 随后的功能障碍,改变血管扩张介质的产生,损害 神经血管偶联反应,促进血脑屏障(BBB)破坏, 微血管稀疏。脑血流量(CBF)下降, 神经炎症导致认知障碍。拟议中的工作是新颖的,因为它将是 第一个证明衰老诱导的内皮衰老是一个关键的贡献, VCID的发病机制。研究结果可能会确定具体的机制, 揭示能够改善CBF和恢复学习的潜在疗法, 记忆提出以下目标:1)确定内皮衰老如何改变 神经血管耦合反应,脑血流和认知老化。工作假设是, 衰老诱导的内皮细胞p16依赖性细胞衰老程序的激活 损害血管扩张功能。据预测,消除衰老的内皮细胞, 细胞,通过基因操作或通过senolytic疗法将恢复神经血管, 功能,改善脑血流量和认知功能。2)确定衰老如何改变 微血管密度和BBB完整性。工作假设是, 内皮细胞p16依赖性细胞衰老程序损害内皮屏障 功能和损害微循环网络的维护。据预测 消除衰老细胞将恢复BBB,减轻神经炎症并增加 老年小鼠微血管密度。3)确定细胞异质性, 衰老内皮细胞与其形态和功能 特色总之,拟议的研究将确定一个基本机制, 控制衰老引起的脑血管变化,最终导致认知障碍。

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 }}

Anna Csiszar其他文献

Anna Csiszar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('Anna Csiszar', 18)}}的其他基金

Chemotherapy-induced vascular cognitive impairment: role of endothelial senescence
化疗引起的血管性认知障碍:内皮衰老的作用
  • 批准号:
    10323272
  • 财政年份:
    2021
  • 资助金额:
    $ 36.25万
  • 项目类别:
Chemotherapy-induced vascular cognitive impairment: role of endothelial senescence
化疗引起的血管性认知障碍:内皮衰老的作用
  • 批准号:
    10539312
  • 财政年份:
    2021
  • 资助金额:
    $ 36.25万
  • 项目类别:
Age-related vascular cognitive impairment: role of endothelial senescence
年龄相关的血管认知障碍:内皮衰老的作用
  • 批准号:
    10671650
  • 财政年份:
    2020
  • 资助金额:
    $ 36.25万
  • 项目类别:
Age-related vascular cognitive impairment: role of endothelial senescence
年龄相关的血管认知障碍:内皮衰老的作用
  • 批准号:
    10453694
  • 财政年份:
    2020
  • 资助金额:
    $ 36.25万
  • 项目类别:
Age-related vascular cognitive impairment: role of endothelial senescence
年龄相关的血管认知障碍:内皮衰老的作用
  • 批准号:
    10222565
  • 财政年份:
    2020
  • 资助金额:
    $ 36.25万
  • 项目类别:
ANIMAL MODEL DEVELOPMENT AND BEHAVIORAL ASSESSMENT (AMD-BA) CORE
动物模型开发和行为评估 (AMD-BA) 核心
  • 批准号:
    10536647
  • 财政年份:
    2019
  • 资助金额:
    $ 36.25万
  • 项目类别:
ANIMAL MODEL DEVELOPMENT AND BEHAVIORAL ASSESSMENT (AMD-BA) CORE
动物模型开发和行为评估 (AMD-BA) 核心
  • 批准号:
    10077913
  • 财政年份:
    2019
  • 资助金额:
    $ 36.25万
  • 项目类别:
Microvascular mechanisms of neuroinflammation: role of Nrf2
神经炎症的微血管机制:Nrf2 的作用
  • 批准号:
    8748331
  • 财政年份:
    2014
  • 资助金额:
    $ 36.25万
  • 项目类别:
Vasoprotection by Caloric Restriction Mimetics in Aging
衰老过程中热量限制模拟物的血管保护作用
  • 批准号:
    8146105
  • 财政年份:
    2010
  • 资助金额:
    $ 36.25万
  • 项目类别:
Vasoprotection by Caloric Restriction Mimetics in Aging
衰老过程中热量限制模拟物的血管保护作用
  • 批准号:
    8320900
  • 财政年份:
    2010
  • 资助金额:
    $ 36.25万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.25万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 36.25万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 36.25万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.25万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 36.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.25万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 36.25万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 36.25万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 36.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 36.25万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了