Bladder Mucosal Dysfunction During Aging
衰老过程中的膀胱粘膜功能障碍
基本信息
- 批准号:10371207
- 负责人:
- 金额:$ 59.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAgeAgingAnatomyAnimalsArchitectureAutophagocytosisBehaviorBiochemicalBioenergeticsBiogenesisBiological AssayBladderBladder ControlBladder DiseasesBladder DysfunctionBladder mucosaCalciumCathepsins BCell AgingCell CommunicationCell surfaceCellsComplexCoupledCytoplasmDataDefectDevelopmentDiagnosisDiseaseDrug TargetingElderlyEsthesiaEtiologyEventExocytosisFibrosisFoundationsFunctional disorderGenus HippocampusHealthHealth Care CostsHomeostasisHydrolaseImageImaging TechniquesImpairmentIncontinenceInstitutionalizationInterdisciplinary StudyLeadLower urinary tractLysosomesMeasurementMeasuresMediator of activation proteinMetabolic PathwayMetforminMitochondriaModalityModelingMolecularMorphologyMuscle functionNervous system structureNeurologicOrganOrganellesOxidative StressPathway interactionsPeptide HydrolasesPhenotypePhysiologyPopulationPositioning AttributeProcessProductionQuality of lifeQuantitative Reverse Transcriptase PCRRattusReactive Oxygen SpeciesResearchResourcesRoleSignal PathwaySignal TransductionSocietiesStressSumSymptomsUrinary IncontinenceUrodynamicsUrothelial CellUrotheliumWestern Blottingafferent nerveage effectage relatedagedanti agingcostdetrusor muscleimprovedin vivoinsightinterdisciplinary approachlower urinary tract symptomsmechanical stimulusmitochondrial dysfunctionprotein degradationreceptorsensory inputside effecttooltranscription factor
项目摘要
Lower urinary tract symptoms (LUTS), in particular storage symptoms (urinary incontinence) are a
major health related problem in the elderly. Yet, there remains insufficient understanding of how aging alters
normal bladder physiology, and how these changes contribute to the etiology of LUT disorders in the elderly.
Much of research past and present, has focused on detrusor muscle function and changes in the central
neurological control of aging-related LUT function; however, much less is known about the role of the
urothelium (UT) in these events. While previously thought of as a simple barrier, the urothelium communicates
with the CNS via a local urothelial-afferent signaling pathway. Our preliminary data show that aged UT has
altered mitochondrial function, including increased production of reactive oxygen species (ROS), which we
hypothesize leads to lysosomal dysfunction, altered release of mediators, and defects in UT-afferent signaling,
culminating in abnormal urodynamic behavior. Thus, our overall hypothesis is that age-related changes in the
UT and adjacent bladder wall result in a pro-aging cellular phenotype that disrupts UT-cell signaling resulting in
abnormal urodynamic behavior in the elderly.
Our multidisciplinary research team will elucidate the effect of aging and oxidative/lysosomal stress on
urothelial physiology and the impact this has on cross talk between the UT and other cells within the bladder
wall. Using an aging (3-30 mo) rat model, we will in Aim #1 define how changes in bioenergetics and oxidative
stress impact urothelial aging by using functional assays to measure changes in both mitochondrial function
and architecture. In Aim #2, we will determine how lysosomal dysfunction contributes to urothelial aging. Here
we will use stereology as well as biochemical and morphological tools to examine why degradation and
mitophagy are impaired in aging urothelium. In Aim #3, we will determine if increasing mitochondrial/lysosomal
function will enhance UT-signaling and resultant bladder function. We will use a multi-disciplinary approach
including measurement of transmitter release and sophisticated imaging techniques coupled with recording
bladder afferent nerve activity to examine how aging and increased mitochondrial oxidative stress alters UT-
cell communication. In each aim, we will also examine whether treatments (mitotempo; metformin) that reduce
oxidative stress/lysosome dysfunction can improve urothelial (and in vivo bladder function) in aged rats. In
sum, our intriguing preliminary data combined with our extensive expertise and resources places our research
team in a unique position to examine how direct and indirect factors promote UT dysfunction in bladder aging.
下尿路症状(LUTS),特别是储存症状(尿失禁)是一种
项目成果
期刊论文数量(7)
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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Gerard L Apodaca其他文献
Gerard L Apodaca的其他文献
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{{ truncateString('Gerard L Apodaca', 18)}}的其他基金
Role of AJC in umbrella cell function and dysfunction
AJC 在伞细胞功能和功能障碍中的作用
- 批准号:
10655616 - 财政年份:2021
- 资助金额:
$ 59.63万 - 项目类别:
Role of AJC in umbrella cell function and dysfunction
AJC 在伞细胞功能和功能障碍中的作用
- 批准号:
10482413 - 财政年份:2021
- 资助金额:
$ 59.63万 - 项目类别:
Role of AJC in umbrella cell function and dysfunction
AJC 在伞细胞功能和功能障碍中的作用
- 批准号:
10277473 - 财政年份:2021
- 资助金额:
$ 59.63万 - 项目类别:
Role of PIEZO Channels in Bladder Function and Dysfunction
PIEZO 通道在膀胱功能和功能障碍中的作用
- 批准号:
10662385 - 财政年份:2019
- 资助金额:
$ 59.63万 - 项目类别:
Role of PIEZO Channels in Bladder Function and Dysfunction
PIEZO 通道在膀胱功能和功能障碍中的作用
- 批准号:
9815767 - 财政年份:2019
- 资助金额:
$ 59.63万 - 项目类别:
Role of PIEZO Channels in Bladder Function and Dysfunction
PIEZO 通道在膀胱功能和功能障碍中的作用
- 批准号:
10417071 - 财政年份:2019
- 资助金额:
$ 59.63万 - 项目类别:
Role of PIEZO Channels in Bladder Function and Dysfunction
PIEZO 通道在膀胱功能和功能障碍中的作用
- 批准号:
10187555 - 财政年份:2019
- 资助金额:
$ 59.63万 - 项目类别:
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