Mechanisms of the Age-related Alterations in Lymphatic Pumping
淋巴泵随年龄变化的机制
基本信息
- 批准号:7669195
- 负责人:
- 金额:$ 29.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-08-15 至 2013-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdrenergic AgonistsAdultAffectAgeAgingAging-Related ProcessAnimalsBedsBiologyBlood CirculationBlood Plasma VolumeBlood capillariesBody FluidsBody RegionsCa(2+)-Transporting ATPaseCalciumCaliberCellsCentral VeinCharacteristicsClinicalComputersContractsDataDevelopmentEdemaEffectivenessElderlyEndoplasmic ReticulumEndothelial CellsEndotheliumExperimental ModelsFatty acid glycerol estersFluorescence MicroscopyFreezingFunctional disorderFutureGenerationsGenesGoalsHeterogeneityHomeostasisHumanImageImmunityIn SituInbred F344 RatsInflammation MediatorsInjuryIntercellular FluidIsometric ExerciseIsotonic ExerciseKnowledgeLengthLifeLinkLiquid substanceLymphLymphaticLymphatic SystemLymphatic vesselLymphocyteLymphoid TissueMYLK geneMeasurementMeasuresMechanicsMediatingMesenteryMicrofilamentsModelingMolecularMonitorMuscleMuscle CellsNatureNitrogenOrganismOutputPathway interactionsPatternPhysiologicalPlayPopulationPreparationPropertyProteinsProtocols documentationPumpRNARattusReactionRegulationRelative (related person)ResearchResistanceRoleRouteSkinSmooth MuscleSpeedStretchingStudy SectionSubstance PSystemTechniquesTestingThin FilamentThoracic DuctTissuesTransfectionTransportationTropomyosinVelocimetriesWestern BlottingWorkabsorptionage effectage relatedagedbasebody systemcaldesmoncapillarydesigngenetic regulatory proteinimprovedinnovationinsightinterestlymph flowlymph nodeslymphatic pumpmRNA Expressionmacromoleculemeetingsneoplastic cellnoveloverexpressionparticlepressureresearch and developmentresearch studyresponseshear stresstool
项目摘要
DESCRIPTION (provided by applicant): The major task of the lymphatic system is lymph transport. This system of vessels and nodes is designed to transport fluid, soluble molecules and cells from the interstitium through the lymph nodes to the central veins. The lymphatic system plays important roles in body fluid circulation, macromolecular homeostasis, fat absorption, and immunity. Although all of these body systems are affected by aging, the effects of aging on the lymphatic transport component of any of these body functions are unknown. Particularly, very little is known about the age-related alterations of phasic contractions of the lymphatics, which are critical to the generation of lymph flow. Transporting lymphatics work in a "self-regulatory mode" when their contractility constantly adjusts to the local fluid loads through pressure and flow dependent regulatory mechanisms. The central hypothesis of this proposal is that aging modulates the pressure and flow-dependent regulatory mechanisms in lymphatics. This will result in a regression of the functional adaptive reserves in lymphatic contractility due to the eNOS/iNOS disbalances along with alterations in calcium sensitivity and crossbridge activation mechanisms in lymphatics. Such age-related changes in lymph transport system could diminish the ability of lymphatics to provide adequate lymph transport component for many body functions. The specific aims are: 1) To determine the age-related changes in the sensitivity of lymphatic vessels to transmural pressure and to evaluate their adaptive contractile reserves, 2) To determine the age-related changes in the active mechanical properties of the lymphatic vessels, 3) To determine the age-related changes in flow/walls shear stress profiles in situ and in their sensitivity to imposed flow in isolated lymphatic vessels, 4) To investigate the molecular mechanisms responsible for age-related alterations of lymphatic contractility and to develop an experimental model to improve the diminished lymphatic contractility in aged lymphatics. Mesenteric lymphatics and thoracic duct from 9 and 24 mo rats (Fischer-344 NIA) will be used for all proposed studies. We anticipate that changes in the contractile and regulatory protein components and/or endothelium cell dysfunction are the basis for the impaired pressure/flow-induced functional responses of the aged lymphatics. The results of this research will provide the missing link between the age- related processes in the different tissues and the age-related differential changes in the ability of lymphatics to provide the adequate transport of lymph from them in elderly organisms. Data from this proposal will also provide the basic knowledge for the ways to improve lymphatic transport that is compromised during aging.
Narrative: These studies will provide important new information on how aging alters lymphatic pumping in the elderly. The development of the proposed experimental model, together with novel scientific knowledge obtained in these studies, will provide a scientific basis for the development of future therapies to treat the edema that commonly occurs in the elderly population, impairing the functioning of different tissues.
描述(由申请人提供):淋巴系统的主要任务是淋巴运输。这个由血管和淋巴结组成的系统旨在将液体、可溶性分子和细胞从间质通过淋巴结输送到中央静脉。淋巴系统在体液循环、大分子稳态、脂肪吸收和免疫等方面发挥着重要作用。尽管所有这些身体系统都受到衰老的影响,但衰老对这些身体功能的淋巴运输成分的影响尚不清楚。特别是,我们对淋巴管阶段性收缩的年龄相关改变知之甚少,而淋巴管阶段性收缩对淋巴流的产生至关重要。当运输淋巴管的收缩能力通过压力和流量依赖的调节机制不断适应局部流体负荷时,它们以“自我调节模式”工作。该建议的中心假设是衰老调节淋巴中压力和流量依赖的调节机制。这将导致淋巴收缩功能适应性储备的回归,这是由于eNOS/iNOS失衡以及淋巴中钙敏感性和交叉桥激活机制的改变。这种与年龄相关的淋巴运输系统变化可能会降低淋巴管为许多身体功能提供足够淋巴运输成分的能力。具体目标是:1)确定淋巴管对跨壁压力敏感性的年龄相关变化,并评估其适应性收缩储备;2)确定淋巴管主动力学性能的年龄相关变化;3)确定原位流动/壁剪切应力剖面的年龄相关变化及其对孤立淋巴管施加流量的敏感性。4)探讨年龄相关淋巴细胞收缩能力改变的分子机制,建立改善老年淋巴细胞收缩能力下降的实验模型。9个月和24个月大鼠(fisher -344 NIA)的肠系膜淋巴管和胸导管将用于所有拟议的研究。我们预计,收缩和调节蛋白成分的变化和/或内皮细胞功能障碍是老年淋巴系统压力/血流诱导的功能反应受损的基础。这项研究的结果将提供不同组织中与年龄相关的过程之间缺失的联系,以及老年生物体中淋巴管提供足够的淋巴运输能力的年龄相关的差异变化。这一建议的数据也将为如何改善在衰老过程中受损的淋巴运输提供基础知识。
项目成果
期刊论文数量(0)
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ANATOLIY A GASHEV其他文献
ANATOLIY A GASHEV的其他文献
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{{ truncateString('ANATOLIY A GASHEV', 18)}}的其他基金
Bidirectional Regulatory Interactions Between Lymph Vessel and Adjacent Tissues
淋巴管与邻近组织之间的双向调节相互作用
- 批准号:
8919518 - 财政年份:2014
- 资助金额:
$ 29.63万 - 项目类别:
Mechanisms of the Age-related Alterations in Lymphatic Pumping
淋巴泵随年龄变化的机制
- 批准号:
8113173 - 财政年份:2008
- 资助金额:
$ 29.63万 - 项目类别:
Mechanisms of the Age-related Alterations in Lymphatic Pumping
淋巴泵随年龄变化的机制
- 批准号:
7460037 - 财政年份:2008
- 资助金额:
$ 29.63万 - 项目类别:
Mechanisms of the Age-related Alterations in Lymphatic Pumping
淋巴泵随年龄变化的机制
- 批准号:
7904813 - 财政年份:2008
- 资助金额:
$ 29.63万 - 项目类别:
Mechanisms of the Age-related Alterations in Lymphatic Pumping
淋巴泵随年龄变化的机制
- 批准号:
8306209 - 财政年份:2008
- 资助金额:
$ 29.63万 - 项目类别:
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