The Role of mitochondria in Age-Related Hearing Loss
线粒体在年龄相关性听力损失中的作用
基本信息
- 批准号:9014535
- 负责人:
- 金额:$ 36.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-03-01 至 2018-02-28
- 项目状态:已结题
- 来源:
- 关键词:AffectAge-YearsAgingAging-Related ProcessAllelesApoptosisApoptoticCBA/CaJ MouseCDH23 geneCaloric RestrictionCell DeathCell physiologyCellsCochleaDevelopmentDiseaseElderlyGenesGeneticGoalsHair CellsHalf-LifeHearingHearing AidsHumanInterventionLabyrinthLongevityMammalsMeasurementMediatingMetabolicMitochondriaModelingMolecularMouse StrainsMusMutationNADPOxidation-ReductionOxidative StressPathway interactionsPlayPopulationPresbycusisPreventionPrevention strategyPreventiveProcessReportingResistanceRoleSensory DisordersStressTestingTherapeuticage relateddesigneffective therapyexon skippingimprovedinterestmitochondrial dysfunctionmouse modelnovelnovel strategiespreventresearch studyresponsetherapeutic target
项目摘要
DESCRIPTION (provided by applicant): Age-related hearing loss (AHL, also known as presbycusis) is a universal feature of mammalian aging and is the most common sensory disorder in the elderly population. Molecular mechanisms of AHL are poorly understood, and there are currently no known preventive strategies. We have recently shown that AHL in B6 mice can be prevented by a mutation in the pro-apoptotic gene Bak, a central player in the mitochondrial pathway of apoptosis. We and others have also shown that caloric restriction (CR), the only intervention known to retard aging and extend maximum lifespan in mammals, has a marked inhibitory effect on some mouse models of AHL, and that this effect requires the mitochondrial sirtuin Sirt3. CR improves mitochondrial function, reduces oxidative stress in the cochlea, and prevents age-related cochlear apoptosis. Our central hypothesis is that mitochondrial dysfunction plays a causal role in AHL, and that CR induces Sirt3-dependent metabolic shifts in the cochlea that prevent age-related mitochondrial dysfunction and AHL. Thus, this revised application proposes experiments designed to establish the role and mechanisms of mitochondrial dysfunction in mouse models of AHL and its prevention by CR. In Specific Aim 1, we propose to determine the role of Bak-mediated mitochondrial apoptosis in AHL. Because our previous studies have been performed in B6 mice that carry a cdh23 mutation, we propose to test the role of Bak in two models of AHL that carry a wild-type cdh23 locus, B6.CAST+ahl and CBA/J. In Specific Aim 2 we propose to determine the role of and mechanism of mitochondria in the CR-mediated prevention of AHL. These studies will focus on the role of Sirt3, and its ability to increase oxidative stress resistance and block mitochondrial apoptosis in response to CR.
描述(由申请人提供):听觉相关性听力损失(阿勒,也称为老年性耳聋)是哺乳动物衰老的普遍特征,是老年人群中最常见的感觉障碍。阿勒的分子机制知之甚少,目前还没有已知的预防策略。我们最近发现,B6小鼠的阿勒可以通过促凋亡基因巴克的突变来预防,该基因是线粒体凋亡途径中的核心参与者。我们和其他人还表明,热量限制(CR),唯一已知的干预措施,以延缓衰老和延长最大寿命的哺乳动物,有一个显着的抑制作用,对一些小鼠模型的阿勒,这种效果需要线粒体sirtuin Sirt 3。CR改善线粒体功能,减少耳蜗中的氧化应激,并防止年龄相关的耳蜗细胞凋亡。我们的中心假设是线粒体功能障碍在阿勒中起因果作用,并且CR诱导耳蜗中的Sirt 3依赖性代谢转变,从而防止年龄相关的线粒体功能障碍和阿勒。因此,本修订申请提出了旨在确定阿勒小鼠模型中线粒体功能障碍的作用和机制以及CR预防的实验。在具体目标1中,我们建议确定Bak-mediated线粒体凋亡在阿勒中的作用。由于我们以前的研究已经进行了B6小鼠携带cdh 23突变,我们建议测试巴克的作用,在两个模型的阿勒携带野生型cdh 23基因座,B6. CAST+阿勒和CBA/J。在具体目标2,我们建议确定的作用和机制的线粒体在CR介导的预防阿勒。这些研究将集中在Sirt 3的作用,以及其增加氧化应激抗性和阻断线粒体凋亡以响应CR的能力。
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 }}
TOMAS ALBERTO PROLLA其他文献
TOMAS ALBERTO PROLLA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('TOMAS ALBERTO PROLLA', 18)}}的其他基金
Determination of circulation factors that mediate the health benefits of exercise in mitochondrial aging
确定调节运动对线粒体衰老健康益处的循环因素
- 批准号:
10011425 - 财政年份:2020
- 资助金额:
$ 36.76万 - 项目类别:
The Role of mitochondria in Age-Related Hearing Loss
线粒体在年龄相关性听力损失中的作用
- 批准号:
8292770 - 财政年份:2012
- 资助金额:
$ 36.76万 - 项目类别:
The Role of mitochondria in Age-Related Hearing Loss
线粒体在年龄相关性听力损失中的作用
- 批准号:
8433346 - 财政年份:2012
- 资助金额:
$ 36.76万 - 项目类别:
The Role of mitochondria in Age-Related Hearing Loss
线粒体在年龄相关性听力损失中的作用
- 批准号:
8607929 - 财政年份:2012
- 资助金额:
$ 36.76万 - 项目类别:
The Role of mitochondria in Age-Related Hearing Loss
线粒体在年龄相关性听力损失中的作用
- 批准号:
8803779 - 财政年份:2012
- 资助金额:
$ 36.76万 - 项目类别:
Oxidative Stress, p66shc and the Aging Process
氧化应激、p66shc 和衰老过程
- 批准号:
7012217 - 财政年份:2005
- 资助金额:
$ 36.76万 - 项目类别:
Oxidative Stress, p66shc and the Aging Process
氧化应激、p66shc 和衰老过程
- 批准号:
7921172 - 财政年份:2005
- 资助金额:
$ 36.76万 - 项目类别:
Oxidative Stress, p66shc and the Aging Process
氧化应激、p66shc 和衰老过程
- 批准号:
6866933 - 财政年份:2005
- 资助金额:
$ 36.76万 - 项目类别:
Oxidative Stress, p66shc and the Aging Process
氧化应激、p66shc 和衰老过程
- 批准号:
7365092 - 财政年份:2005
- 资助金额:
$ 36.76万 - 项目类别:
Oxidative Stress, p66shc and the Aging Process
氧化应激、p66shc 和衰老过程
- 批准号:
7569454 - 财政年份:2005
- 资助金额:
$ 36.76万 - 项目类别:
相似海外基金
PREDICTING CARIES RISK IN UNDERSERVED CHILDREN, FROM TODDLERS TO THE SCHOOL-AGE YEARS, IN PRIMARY HEALTHCARE SETTINGS
预测初级医疗保健机构中从幼儿到学龄儿童的龋齿风险
- 批准号:
10361268 - 财政年份:2021
- 资助金额:
$ 36.76万 - 项目类别:
Predicting Caries Risk in Underserved Children, from Toddlers to the School-Age Years, in Primary Healthcare Settings
预测初级医疗机构中服务不足的儿童(从幼儿到学龄儿童)的龋齿风险
- 批准号:
9751077 - 财政年份:2011
- 资助金额:
$ 36.76万 - 项目类别:
Predicting Caries Risk in Underserved Children, from Toddlers to the School-Age Years, in Primary Healthcare Settings
预测初级医疗机构中服务不足的儿童(从幼儿到学龄儿童)的龋齿风险
- 批准号:
9976990 - 财政年份:2011
- 资助金额:
$ 36.76万 - 项目类别:
Predicting Caries Risk in Underserved Children, from Toddlers to the School-Age Years, in Primary Healthcare Settings
预测初级医疗机构中服务不足的儿童(从幼儿到学龄儿童)的龋齿风险
- 批准号:
10457019 - 财政年份:2011
- 资助金额:
$ 36.76万 - 项目类别:
Predicting Caries Risk in Underserved Children, from Toddlers to the School-Age Years, in Primary Healthcare Settings
预测初级医疗机构中服务不足的儿童(从幼儿到学龄儿童)的龋齿风险
- 批准号:
10213006 - 财政年份:2011
- 资助金额:
$ 36.76万 - 项目类别: