Immunometabolic regulation of bone inflammaging
Immunometabolic regulation of bone inflammaging
批准号:
10430514
负责人:
VISHWA DEEP DIXIT
金额:
$50.25万
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
项目状态:
未结题
起止时间:
2022-06-15 至 2027-03-31
关键词:
AddressAdipocytesAdipose tissueAgeAgingBiological AvailabilityBone MarrowCatecholaminesCellsChronicChronic DiseaseCoupledDataDown-RegulationElderlyEnzymesEventFatty acid glycerol estersFractureGenerationsGoalsHematopoiesisHematopoietic Stem Cell TransplantationHumanHydrolysisImmuneImmune systemImpairmentInflammagingInflammasomeInflammationKnock-inKnockout MiceLinkLipidsLipolysisLoxP-flanked alleleMarrowMediatingMembraneMetabolicMetabolic dysfunctionMonoamine Oxidase AMusMyeloid CellsNerveNerve DegenerationNeuroimmuneNorepinephrineObesityOrganOsteitisOsteoclastsOsteoporosisPost-Translational RegulationProcessRadiationRegulationResearchSympathetic Nervous SystemSynaptic VesiclesTestingThymus GlandTimeTissuesTranscriptional ActivationTranscriptional RegulationTransgenic MiceTriglyceridesTyrosine 3-Monooxygenaseadipokinesage relatedagedbasebody systembonebone healthbone lossbone strengthcortical bonecytokinedisabilityfatty acid oxidationfrailtyhealthspanhuman modelimmune reconstitutionimprovedmacrophagemass spectrometric imagingmouse modelnerve supplynovel strategiespreventprimary lymphoid organprotein expressionregenerativeskeletalstem cell engraftmentsubstantia spongiosasuccess
中文摘要
项目总结
老年人多器官的年龄相关性炎症和异位脂质堆积与骨骼相关
失落、虚弱和慢性病。例如,骨骼和胸腺是主要的主要淋巴器官,
在人类和小鼠模型中逐渐积累异位脂肪和脂肪细胞。富有同情心的
神经系统(SNS)通过突触后局部释放儿茶酚胺来调节所有器官系统
在没有完成控制转录的事件所需的时间延迟的情况下快速地形成小泡
特定细胞因子或脂肪因子的激活或翻译后调节。释放的儿茶酚胺
来自SNS的各种局部组织中的缝隙是脂肪酸氧化所必需的,这一过程在老年人中受到损害。
这项提案旨在解决的关键问题是:a)衰老如何导致异位脂质在
骨髓?B)异位脂质的增加是否是骨增加的关联触发因素
衰老过程中出现的炎症和骨质疏松。C)是否可以防止骨丢失和异位堆积
通过瞄准连接免疫-代谢串扰的机制来衰老?这些问题源于我们的
发现衰老与去甲肾上腺素(NE)的降解增加有关
儿茶酚胺降解酶单胺氧化酶A的表达的长期目标是
该项目旨在破译控制骨炎的神经免疫串扰,并以此为目标。
机制,以开发新的方法,以维持或增强老年人的骨功能。
英文摘要
PROJECT SUMMARY
Age-related inflammation and accumulation of ectopic lipid in multiple organs in elderly is associated with bone
loss, frailty and chronic diseases. For example, bone and thymus are the major primary lymphoid organs that
progressively accumulate ectopic lipid and adipocytes in humans and mouse models. The sympathetic
nervous system (SNS) regulates all organ systems by localized release of catecholamines from post-synaptic
vesicles in a rapid fashion without the time-lag required to complete events that control transcriptional
activation or post-translational regulation of specific cytokines or adipokines. The catecholamines released
from SNS in various local tissue niches is required for fatty acid oxidation, a process that is impaired in elderly.
The key questions this proposal aims to address is: A) How does aging cause accumulation of ectopic lipid in
bone marrow? B) Whether increase in ectopic lipid serves as an associative trigger for increase in bone
inflammation and osteoporosis seen during aging. C) Can one prevent bone loss and ectopic accumulation in
aging by targeting the mechanisms that link immune-metabolic crosstalk? These questions emanate from our
discovery that aging is associated with increased degradation of norepinephrine (NE) due to elevated
expression of Monoamine Oxidase A (MAOA), a catecholamine degradation enzyme. The long-term goal of
this project is to decipher neuro-immune crosstalk that controls bone inflammation and to target this
mechanism to develop new approaches to maintain or enhance bone function in elderly.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Caloric restriction-driven immunometabolic checkpoints of inflammation
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批准号:10457565
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项目类别:
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资助金额:$58.39万
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财政年份:2022
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负责人:VISHWA DEEP DIXIT
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依托单位:
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依托单位:
Caloric restriction-driven immunometabolic checkpoints of inflammation
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批准号:10656332
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资助金额:$55.01万
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财政年份:2022
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负责人:VISHWA DEEP DIXIT
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依托单位:
Immunometabolic regulation of bone inflammaging
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批准号:10641819
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资助金额:$46.16万
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财政年份:2022
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负责人:VISHWA DEEP DIXIT
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依托单位:
Yale Murine-TMC on Immune Cell Senescence Derived Inflammation
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批准号:10553032
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项目类别:
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资助金额:$166.49万
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财政年份:2022
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负责人:VISHWA DEEP DIXIT
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依托单位:
Impact of dysbiosis on the development of age-related inflammation
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批准号:10331167
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项目类别:
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资助金额:$7.06万
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财政年份:2020
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依托单位:
Impact of dysbiosis on the development of age-related inflammation
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批准号:10396668
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项目类别:
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资助金额:$41.88万
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财政年份:2020
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依托单位:
Impact of dysbiosis on the development of age-related inflammation
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批准号:10667392
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项目类别:
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资助金额:$7.06万
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财政年份:2020
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负责人:VISHWA DEEP DIXIT
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依托单位:
Impact of dysbiosis on the development of age-related inflammation
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批准号:10259710
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项目类别:
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资助金额:$41.88万
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财政年份:2020
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负责人:VISHWA DEEP DIXIT
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依托单位:
Impact of Ketone Metabolites on Inflammasome Deactivation in Gout
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批准号:10091969
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项目类别:
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资助金额:$35.74万
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财政年份:2017
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负责人:VISHWA DEEP DIXIT
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依托单位:
Impact of Ketone Metabolites on Inflammasome Deactivation in Gout
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批准号:9216426
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项目类别:
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资助金额:$36.85万
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财政年份:2017
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负责人:VISHWA DEEP DIXIT
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依托单位:
Impact of FGF21 on healthspan and lifespan
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批准号:9148504
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项目类别:
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资助金额:$205.42万
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财政年份:2016
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负责人:VISHWA DEEP DIXIT
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依托单位:
Impact of FGF21 on healthspan and lifespan
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批准号:9901985
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项目类别:
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资助金额:$29.1万
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财政年份:2016
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负责人:VISHWA DEEP DIXIT
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依托单位:
Thymic adipogenesis and age-related thymic demise
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批准号:8818658
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项目类别:
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资助金额:$41.63万
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财政年份:2014
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负责人:VISHWA DEEP DIXIT
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依托单位:
Thymic adipogenesis and age-related thymic demise
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批准号:9171367
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项目类别:
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资助金额:$61.63万
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财政年份:2014
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负责人:VISHWA DEEP DIXIT
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依托单位:
Thymic adipogenesis and age-related thymic demise
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批准号:8960920
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项目类别:
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资助金额:$41.63万
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财政年份:2014
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负责人:VISHWA DEEP DIXIT
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依托单位:
Impact of CR on inflammasome driven immune-metabolic interactions.
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批准号:8575882
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项目类别:
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资助金额:$26.71万
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财政年份:2013
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依托单位:
Impact of CR on inflammasome driven immune-metabolic interactions.
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批准号:8730078
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项目类别:
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资助金额:$25.75万
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财政年份:2013
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负责人:VISHWA DEEP DIXIT
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依托单位:
Inflammasomes and the mechanism of thymic demise in aging
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批准号:8669901
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项目类别:
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资助金额:$34.13万
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财政年份:2013
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负责人:VISHWA DEEP DIXIT
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依托单位:
Inflammasomes and the mechanism of thymic demise in aging
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批准号:8852033
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项目类别:
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资助金额:$41.29万
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财政年份:2013
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负责人:VISHWA DEEP DIXIT
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依托单位:
国内基金
海外基金
支链氨基酸代谢紊乱调控“Adipocytes - Macrophages Crosstalk”诱发2型糖尿病脂肪组织功能和结构障碍的作用及机制
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批准号:81970721
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项目类别:面上项目
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资助金额:55.0万元
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批准年份:2019
-
负责人:陶凌
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依托单位: