Novel longevity enhancing pathways regulated by mTOR

mTOR 调控的新长寿途径

基本信息

  • 批准号:
    10446243
  • 负责人:
  • 金额:
    $ 39.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-01 至 2027-03-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT/SUMMARY Inhibitors of the mTOR pathway are among the most promising interventions to target age-related dysfunction, however, there is a critical need to further define the pro longevity effects to facilitate clinical development of mTOR inhibitors. The current proposal will significantly advance this effort providing new targets for intervention and novel markers to monitor individual responses to mTOR inhibition. The overarching goal of this research program is to develop a mechanistic understanding of novel downstream targets of rapamycin, in order to facilitate safer and more effective strategies to promote healthy aging. Cellular senescence occurs in both somatic and stem cell populations and contributes to age-related dysfunction, and our laboratory has shown that mTOR inhibition using rapamycin, can prevent entry into the senescent state. The mTOR pathway also regulates senescence a n d pluripotency in a variety of stem cell populations. The central hypothesis of the application is that mTOR inhibition by rapamycin prevents senescence and enhances pluripotency by increasing the lncRNA H19. The rationale for this hypothesis is our observation that rapamycin increases levels of the non- coding RNA (lncRNA) H19. We find that levels of H19 decrease during senescence and in pluripotent cells. H19 plays a central role during development and differentiation, and maintenance of adult stem cell populations. Rapamycin increases H19 levels, prevents senescence and maintains pluripotency. The results suggest that increasing H19 levels in response to mTOR inhibition may play a dual role, inhibiting senescence while simultaneously increasing pluripotency in adult stem cell populations. The proposed work will provide transformative data regarding a novel mechanism for lifespan extension and improvement of late-life function in multiple tissues.
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项目成果

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CHRISTIAN SELL其他文献

CHRISTIAN SELL的其他文献

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{{ truncateString('CHRISTIAN SELL', 18)}}的其他基金

Novel longevity enhancing pathways regulated by mTOR
mTOR 调控的新长寿途径
  • 批准号:
    10649541
  • 财政年份:
    2022
  • 资助金额:
    $ 39.63万
  • 项目类别:
Novel longevity enhancing pathways regulated by mTOR
mTOR 调控的新长寿途径
  • 批准号:
    10711017
  • 财政年份:
    2022
  • 资助金额:
    $ 39.63万
  • 项目类别:
Novel longevity enhancing pathways regulated by mTOR
mTOR 调控的新长寿途径
  • 批准号:
    10358671
  • 财政年份:
    2021
  • 资助金额:
    $ 39.63万
  • 项目类别:
Novel models for longevity research
长寿研究的新模型
  • 批准号:
    8243150
  • 财政年份:
    2011
  • 资助金额:
    $ 39.63万
  • 项目类别:
Novel models for longevity research
长寿研究的新模型
  • 批准号:
    8331435
  • 财政年份:
    2011
  • 资助金额:
    $ 39.63万
  • 项目类别:
Role of IGF-1 in Modulation of Longevity
IGF-1 在长寿调节中的作用
  • 批准号:
    7247142
  • 财政年份:
    2005
  • 资助金额:
    $ 39.63万
  • 项目类别:
Role of IGF-1 in Modulation of Longevity
IGF-1 在长寿调节中的作用
  • 批准号:
    7455898
  • 财政年份:
    2005
  • 资助金额:
    $ 39.63万
  • 项目类别:
Role of IGF-1 in Modulation of Longevity
IGF-1 在长寿调节中的作用
  • 批准号:
    6975030
  • 财政年份:
    2005
  • 资助金额:
    $ 39.63万
  • 项目类别:
Role of IGF-1 in Modulation of Longevity
IGF-1 在长寿调节中的作用
  • 批准号:
    7662267
  • 财政年份:
    2005
  • 资助金额:
    $ 39.63万
  • 项目类别:
Role of IGF-1 in Modulation of Longevity
IGF-1 在长寿调节中的作用
  • 批准号:
    7460474
  • 财政年份:
    2005
  • 资助金额:
    $ 39.63万
  • 项目类别:
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