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
- 来源:
- 关键词:AgingAlzheimer&aposs DiseaseCCCTC-binding factorCDKN2A geneCell AgingCell CompartmentationCellsClinicalComplexDataDevelopmentDiseaseDrug usageEZH2 geneElderlyFDA approvedFRAP1 geneFunctional disorderGenetic TranscriptionGoalsGrantH19 geneHeart failureHumanInflammationInterventionLaboratoriesLongevityMaintenanceMediatingMediator of activation proteinMetabolicMicroRNAsModelingMonitorMusPathway interactionsPharmaceutical PreparationsPhosphotransferasesPlayPromoter RegionsRNARegulationReporterResearchRoleSignal TransductionSirolimusSomatic CellTP53 geneTestingTissuesUntranslated RNAWorkZinc Fingersadult stem cellage relatedcell typechromatin modificationclinical developmentgene repressionhealthy agingimmune functionimprovedin vivoindividual responseinhibitormTOR InhibitormTOR inhibitionmembernovelnovel markerpluripotencypreventprogramspromoterresponsesenescenceside effectstem cell functionstem cell populationstem cells
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.
抽象/总结
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: