Targeting macrophage polarization to optimize muscle regrowth from disuse atrophy
靶向巨噬细胞极化以优化废用性萎缩的肌肉再生
基本信息
- 批准号:10228828
- 负责人:
- 金额:$ 63.43万
- 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:2020-09-15 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdoptedAerobic ExerciseAgeAgingAnti-Inflammatory AgentsAreaAttenuatedBone MarrowBone Marrow CellsBone Marrow TransplantationCell physiologyCellsChronicCoupledDataDefectDevelopmentDisuse AtrophyEffectivenessElderlyEventFibrosisFoundationsFractureFunctional disorderGenomicsGrowth FactorHealthHematopoieticHindlimbHindlimb SuspensionHumanIGF1 geneImmuneImmune systemImmunofluorescence ImmunologicImmunotherapyImpairmentIndividualInjuryIntramuscularIntramuscular InjectionsLeadMacrophage Colony-Stimulating FactorMetabolic DiseasesMethodologyMusMuscleMuscle functionOperative Surgical ProceduresPhenotypePopulationPublishingRecoveryRecovery of FunctionResolutionRunningSeriesSignal TransductionSkeletal MuscleTestingTherapeuticTimeToxinTransplantationage relatedagedaging populationbasebonebone agingcytokinedisabilityevidence baseexperimental studyfall riskfallsimmunoregulationimprovedloss of functionmacrophagemonocytemouse geneticsmouse modelmuscle agingmuscle regenerationnovelpre-clinicalpreventrecruitrepairedresponserestorationsarcopeniasingle-cell RNA sequencing
项目摘要
Abstract
Muscle recovery following a disuse event is impaired in many older adults which could increase the risk for falls,
fractures and disability. We have shown that muscle macrophages are dysregulated during the regrowth period
following a disuse event in aged muscle. Therefore, we have proposed a series of elegant, pre-clinical mouse
experiments to determine the effectiveness of various immunomodulating therapeutics and identify specific
mechanisms underlying age-related muscle immune dysregulation in skeletal muscle during regrowth from
disuse. We will utilize state-of-the-art approaches to phenotype muscle macrophages (FACS, single cell RNA
sequencing, immunofluorescence) coupled with mouse genetics and bone transfer experiments to extensively
address these questions. The data generated will be the first of its kind identifying the mechanisms underlying
macrophage dysregulation in aged muscle during regrowth following disuse atrophy while also testing if
immunomodulation amplifies muscle and functional recovery in the old.
抽象的
许多老年人都会损害废弃事件后的肌肉恢复,这可能会增加跌倒的风险,
断裂和残疾。我们已经表明,在再生期间,肌肉巨噬细胞失调
在老年肌肉中废弃事件之后。因此,我们提出了一系列优雅的临床前鼠标
实验以确定各种免疫调节疗法的有效性并确定特定
在再生期间,骨骼肌与年龄相关的肌肉免疫失调的基础机制
废弃。我们将利用表型肌肉巨噬细胞的最先进方法(FACS,单细胞RNA
测序,免疫荧光)与小鼠遗传学和骨转移实验相结合到广泛
解决这些问题。生成的数据将是确定基本机制的同类数据
废除萎缩后再生期间老年肌肉的巨噬细胞失调,同时还测试了是否
免疫调节会放大旧的肌肉和功能恢复。
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)
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Micah J Drummond其他文献
Micah J Drummond的其他文献
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{{ truncateString('Micah J Drummond', 18)}}的其他基金
MicroRNA regulation of chronic inflammation during aging
MicroRNA对衰老过程中慢性炎症的调节
- 批准号:
10817445 - 财政年份:2022
- 资助金额:
$ 63.43万 - 项目类别:
Regulation of macrophage metabolism in aged muscle during recovery
衰老肌肉恢复过程中巨噬细胞代谢的调节
- 批准号:
10622569 - 财政年份:2022
- 资助金额:
$ 63.43万 - 项目类别:
Regulation of macrophage metabolism in aged muscle during recovery
衰老肌肉恢复过程中巨噬细胞代谢的调节
- 批准号:
10460028 - 财政年份:2022
- 资助金额:
$ 63.43万 - 项目类别:
MicroRNA regulation of chronic inflammation during aging
MicroRNA对衰老过程中慢性炎症的调节
- 批准号:
10531053 - 财政年份:2022
- 资助金额:
$ 63.43万 - 项目类别:
Role of immune cells on the growth and recovery of aging muscle
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- 批准号:
10197500 - 财政年份:2019
- 资助金额:
$ 63.43万 - 项目类别:
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