Bladder Mucosal Dysfunction During Aging

衰老过程中的膀胱粘膜功能障碍

基本信息

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)

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 }}

Gerard L Apodaca其他文献

Gerard L Apodaca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('Gerard L Apodaca', 18)}}的其他基金

Resource Development Core
资源开发核心
  • 批准号:
    10747628
  • 财政年份:
    2023
  • 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:
    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:
Bladder Mucosal Dysfunction During Aging
衰老过程中的膀胱粘膜功能障碍
  • 批准号:
    9540177
  • 财政年份:
    2018
  • 资助金额:
    $ 59.63万
  • 项目类别:
Bladder Mucosal Dysfunction During Aging
衰老过程中的膀胱粘膜功能障碍
  • 批准号:
    9897459
  • 财政年份:
    2018
  • 资助金额:
    $ 59.63万
  • 项目类别:

相似国自然基金

靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    0 万元
  • 项目类别:
    面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
  • 批准号:
    2023JJ50274
  • 批准年份:
    2023
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    33 万元
  • 项目类别:
    地区科学基金项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
  • 批准号:
    n/a
  • 批准年份:
    2022
  • 资助金额:
    10.0 万元
  • 项目类别:
    省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
  • 批准号:
    81973577
  • 批准年份:
    2019
  • 资助金额:
    55.0 万元
  • 项目类别:
    面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
  • 批准号:
    81602908
  • 批准年份:
    2016
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
  • 批准号:
    81501928
  • 批准年份:
    2015
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

The Phenomenon of Stem Cell Aging according to Methylation Estimates of Age After Hematopoietic Stem Cell Transplantation
根据造血干细胞移植后甲基化年龄估算干细胞衰老现象
  • 批准号:
    23K07844
  • 财政年份:
    2023
  • 资助金额:
    $ 59.63万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Analysis of Age-dependent Functional Changes in Skeletal Muscle CB1 Receptors by an in Vitro Model of Aging-related Muscle Atrophy
通过衰老相关性肌肉萎缩的体外模型分析骨骼肌 CB1 受体的年龄依赖性功能变化
  • 批准号:
    22KJ2960
  • 财政年份:
    2023
  • 资助金额:
    $ 59.63万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Joint U.S.-Japan Measures for Aging and Dementia Derived from the Prevention of Age-Related and Noise-induced Hearing Loss
美日针对预防与年龄相关和噪声引起的听力损失而导致的老龄化和痴呆症联合措施
  • 批准号:
    23KK0156
  • 财政年份:
    2023
  • 资助金额:
    $ 59.63万
  • 项目类别:
    Fund for the Promotion of Joint International Research (International Collaborative Research)
The Effects of Muscle Fatigability on Gait Instability in Aging and Age-Related Falls Risk
肌肉疲劳对衰老步态不稳定性和年龄相关跌倒风险的影响
  • 批准号:
    10677409
  • 财政年份:
    2023
  • 资助金额:
    $ 59.63万
  • 项目类别:
Characterizing gut physiology by age, frailty, and sex: assessing the role of the aging gut in "inflamm-aging"
按年龄、虚弱和性别表征肠道生理学特征:评估衰老肠道在“炎症衰老”中的作用
  • 批准号:
    497927
  • 财政年份:
    2023
  • 资助金额:
    $ 59.63万
  • 项目类别:
Deciphering the role of osteopontin in the aging eye and age-related macular degeneration
破译骨桥蛋白在眼睛老化和年龄相关性黄斑变性中的作用
  • 批准号:
    10679287
  • 财政年份:
    2023
  • 资助金额:
    $ 59.63万
  • 项目类别:
Role of AGE/RAGEsignaling as a driver of pathological aging in the brain
AGE/RAGE信号传导作为大脑病理性衰老驱动因素的作用
  • 批准号:
    10836835
  • 财政年份:
    2023
  • 资助金额:
    $ 59.63万
  • 项目类别:
Elucidation of the protein kinase NLK-mediated aging mechanisms and treatment of age-related diseases
阐明蛋白激酶NLK介导的衰老机制及年龄相关疾病的治疗
  • 批准号:
    23K06378
  • 财政年份:
    2023
  • 资助金额:
    $ 59.63万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Underlying mechanisms of age-related changes in ingestive behaviors: From the perspective of the aging brain and deterioration of the gustatory system.
与年龄相关的摄入行为变化的潜在机制:从大脑老化和味觉系统退化的角度来看。
  • 批准号:
    23K10845
  • 财政年份:
    2023
  • 资助金额:
    $ 59.63万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Targeting Age-Activated Proinflammatory Chemokine Signaling by CCL2/11 to Enhance Skeletal Muscle Regeneration in Aging
通过 CCL2/11 靶向年龄激活的促炎趋化因子信号传导以增强衰老过程中的骨骼肌再生
  • 批准号:
    478877
  • 财政年份:
    2023
  • 资助金额:
    $ 59.63万
  • 项目类别:
    Operating Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了