Molecular mechanisms of age-related lymphatic dysfunction
年龄相关淋巴功能障碍的分子机制
基本信息
- 批准号:10665795
- 负责人:
- 金额:$ 22.13万
- 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:2022-07-15 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAgingAlzheimer&aposs DiseaseAnatomyAnimalsAntibodiesApoptosisArthritisAutoimmunityBindingBloodBlood VesselsCardiovascular DiseasesCell Differentiation processCell ProliferationCell SeparationCell surfaceCentral Nervous SystemCholesterol HomeostasisChronicClinicalCytoprotectionElderlyEndothelial CellsEventFatty AcidsFemaleFunctional disorderFutureGoalsGrowth FactorHistamine ReleaseHistologicHomologous GeneImmune responseImpairmentIn VitroInfectionInflammationInjuryIntestinesKnockout MiceLigandsLymphaticLymphatic Endothelial CellsLymphatic SystemLymphatic clearanceLymphatic functionLymphedemaMediatingMetabolic syndromeMolecularMusMuscle CellsObesityPIK3CG genePTEN genePathologicPathway interactionsPhenotypePhosphorylationPhysiologicalPlayProliferatingPumpReactive Nitrogen SpeciesReceptor Protein-Tyrosine KinasesRecombinant Vascular Endothelial Growth FactorResearchResearch DesignResolutionRoleSignal TransductionSkinTamoxifenTestingTissuesTransgenic MiceVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-3adaptive immune responseage effectage relatedbody systemconditional knockoutdensityendothelial dysfunctionexperimental studyimprovedin vivoinnovationlymphatic developmentlymphatic dysfunctionlymphatic malformationslymphatic pumplymphatic vesselmacromoleculemalemast cellneutralizing antibodynitrosative stressnovelolder patientpromoterreceptorreceptor bindingresponsetumor
项目摘要
PROJECT SUMMARY/ABSTRACT
Aging results in impaired lymphatic function in a variety of organ systems. This is important because
the lymphatic system has many physiologic functions, and lymphatic abnormalities are implicated in many
pathologic conditions that affect the elderly. However, while it is clear that aging impairs lymphatic function, the
cellular mechanisms that regulate this response remain largely unknown. In addition, the effects of aging on
lymphatic endothelial cell (LEC) response to vascular endothelial growth factor C (VEGFC), downstream
pathways involving Pi3k and Akt signaling, and interactions with lymphatic muscle cells have not been
analyzed.
In previous and preliminary studies, we have found that chronic inflammation in a variety of settings,
including obesity, lymphedema, and aging, results in decreased intracellular LEC Pi3K/Akt signaling. This is
important since LEC Pi3K/Akt signaling is a key regulator of LEC proliferation, differentiation, and function.
These findings are consistent with previous studies demonstrating that abnormalities in Pi3k/Akt signaling also
contribute to age-related blood endothelial dysfunction. In this proposal, we aim to test the hypothesis that
decreased LEC intracellular Pi3k/Akt signaling plays a causal role in age-related lymphatic dysfunction.
Our study is innovative because previous studies have been largely observational and have not
analyzed lymphangiogenic signaling in aging. We have also developed novel transgenic mice that enable us to
selectively analyze the effects of changes in LEC intracellular Pi3k/Akt signaling, thus avoiding the limitations
of previous studies that have relied on the systemic administration of recombinant VEGFC or VEGF-R3
antibodies. Using two aims, we will determine how aging changes LEC Pi3k/Akt signaling in different tissues
and how these changes correlate with lymphatic function. These studies will help us determine how LECs
respond to VEGFC in aging and how these changes modulate response to inflammation and nitrosative stress.
In other studies, we will determine if inhibition of intracellular LEC Pi3k/Akt signaling in young mice can
recapitulate the lymphatic phenotype of old mice. Finally, we will determine if increased LEC Pi3k/Akt signaling
can improve lymphatic function in elderly mice.
At the conclusion of our proposed research, we will have a detailed understanding of the cellular
mechanisms that contribute to age-related lymphatic dysfunction. This understanding will provide the basis for
future studies designed to improve lymphatic function.
项目总结/文摘
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 }}
Babak J Mehrara其他文献
Babak J Mehrara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('Babak J Mehrara', 18)}}的其他基金
Role of epidermis in regulating inflammatory skin manifestations of post-surgical lymphedema
表皮在调节术后淋巴水肿炎症性皮肤表现中的作用
- 批准号:
10606927 - 财政年份:2022
- 资助金额:
$ 22.13万 - 项目类别:
Molecular mechanisms of age-related lymphatic dysfunction
年龄相关淋巴功能障碍的分子机制
- 批准号:
10538995 - 财政年份:2022
- 资助金额:
$ 22.13万 - 项目类别:
Restoration of lymphatic function in postsurgical lymphedema with lymph node transfer
通过淋巴结转移恢复术后淋巴水肿的淋巴功能
- 批准号:
9185953 - 财政年份:2015
- 资助金额:
$ 22.13万 - 项目类别:
Mechanisms of fibrosis and lymphatic dysfunction in post-surgical lymphedema
术后淋巴水肿纤维化和淋巴功能障碍的机制
- 批准号:
8532029 - 财政年份:2012
- 资助金额:
$ 22.13万 - 项目类别:
Mechanisms of fibrosis in post-surgical lymphedema
术后淋巴水肿纤维化的机制
- 批准号:
10063531 - 财政年份:2012
- 资助金额:
$ 22.13万 - 项目类别:
Mechanisms of fibrosis and lymphatic dysfunction in post-surgical lymphedema
术后淋巴水肿纤维化和淋巴功能障碍的机制
- 批准号:
8372995 - 财政年份:2012
- 资助金额:
$ 22.13万 - 项目类别:
Mechanisms of fibrosis and lymphatic dysfunction in post-surgical lymphedema
术后淋巴水肿纤维化和淋巴功能障碍的机制
- 批准号:
8695460 - 财政年份:2012
- 资助金额:
$ 22.13万 - 项目类别:
Mechanisms of fibrosis and lymphatic dysfunction in post-surgical lymphedema
术后淋巴水肿纤维化和淋巴功能障碍的机制
- 批准号:
9094645 - 财政年份:2012
- 资助金额:
$ 22.13万 - 项目类别:
相似海外基金
Interplay between Aging and Tubulin Posttranslational Modifications
衰老与微管蛋白翻译后修饰之间的相互作用
- 批准号:
24K18114 - 财政年份:2024
- 资助金额:
$ 22.13万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The Canadian Brain Health and Cognitive Impairment in Aging Knowledge Mobilization Hub: Sharing Stories of Research
加拿大大脑健康和老龄化认知障碍知识动员中心:分享研究故事
- 批准号:
498288 - 财政年份:2024
- 资助金额:
$ 22.13万 - 项目类别:
Operating Grants
EMNANDI: Advanced Characterisation and Aging of Compostable Bioplastics for Automotive Applications
EMNANDI:汽车应用可堆肥生物塑料的高级表征和老化
- 批准号:
10089306 - 财政年份:2024
- 资助金额:
$ 22.13万 - 项目类别:
Collaborative R&D
関節リウマチ患者のSuccessful Agingに向けたフレイル予防対策の構築
类风湿性关节炎患者成功老龄化的衰弱预防措施的建立
- 批准号:
23K20339 - 财政年份:2024
- 资助金额:
$ 22.13万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Baycrest Academy for Research and Education Summer Program in Aging (SPA): Strengthening research competencies, cultivating empathy, building interprofessional networks and skills, and fostering innovation among the next generation of healthcare workers t
Baycrest Academy for Research and Education Summer Program in Aging (SPA):加强研究能力,培养同理心,建立跨专业网络和技能,并促进下一代医疗保健工作者的创新
- 批准号:
498310 - 财政年份:2024
- 资助金额:
$ 22.13万 - 项目类别:
Operating Grants
Life course pathways in healthy aging and wellbeing
健康老龄化和福祉的生命历程路径
- 批准号:
2740736 - 财政年份:2024
- 资助金额:
$ 22.13万 - 项目类别:
Studentship
I-Corps: Aging in Place with Artificial Intelligence-Powered Augmented Reality
I-Corps:利用人工智能驱动的增强现实实现原地老龄化
- 批准号:
2406592 - 财政年份:2024
- 资助金额:
$ 22.13万 - 项目类别:
Standard Grant
NSF PRFB FY 2023: Connecting physiological and cellular aging to individual quality in a long-lived free-living mammal.
NSF PRFB 2023 财年:将生理和细胞衰老与长寿自由生活哺乳动物的个体质量联系起来。
- 批准号:
2305890 - 财政年份:2024
- 资助金额:
$ 22.13万 - 项目类别:
Fellowship Award
虚弱高齢者のSuccessful Agingを支える地域課題分析指標と手法の確立
建立区域问题分析指标和方法,支持体弱老年人成功老龄化
- 批准号:
23K20355 - 财政年份:2024
- 资助金额:
$ 22.13万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
「ケア期間」に着目したbiological aging指標の開発
开发聚焦“护理期”的生物衰老指数
- 批准号:
23K24782 - 财政年份:2024
- 资助金额:
$ 22.13万 - 项目类别:
Grant-in-Aid for Scientific Research (B)