In vivo and in vitro systems to validate geronic proteins and their mechanisms of action
用于验证老年蛋白及其作用机制的体内和体外系统
基本信息
- 批准号:9422316
- 负责人:
- 金额:$ 53.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-15 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:14 year oldAddressAgeAgingAging-Related ProcessAlcohol or Other Drugs useAlzheimer&aposs DiseaseAnimalsAttentionBehaviorBehavioralBiologyBloodBrainCaloric RestrictionCardiacCardiovascular DiseasesCardiovascular systemCell AgingChronic DiseaseCognitiveCognitive agingCommunicationComplexDataDiabetes MellitusElderlyEmotionalEvaluationEventFibroblastsGenotypeHealthHormonesHumanHungerHypothalamic structureImpairmentIn VitroIndividualInterventionIsoproterenolLearningLettersLongevityMalignant NeoplasmsMediatingMemoryModelingMorbidity - disease rateMusMyocardiumNeuronsNoseOxytocinParabiosisParkinson DiseasePeptidesPeripheralPhysiologicalPlasmaPreparationPrimatesProcessProteinsProteomicsPublishingRejuvenationResearch PersonnelRodentRoleSerum ProteinsShort-Term MemorySignal TransductionSocietiesSystemTestingThallium Myocardial Perfusion Imaging Stress TestTimeTissuesWorkage relatedagedaging populationbody systembonecardiovascular healthclinically relevantcohortdifferential expressionimmune functionin vivoinsightmiddle agemortalitymouse modelnonhuman primate
项目摘要
Late onset chronic diseases associated with aging, including cardiovascular disorders, Alzheimer's and
Parkinson's disease, diabetes and tissue malignancies, are the leading causes of morbidity and mortality
creating the greatest emotional and financial burden on the individual and society. As the aging population
continues to expand, late onset chronic diseases will further dominate the attention of biomedicine. We
have been pursuing the role of the brain circuits and humoral factors in health and aging. We have identified
the hypothalamus as an intersection point between CNS and peripheral tissue communications, defined serum
proteins differentially expressed in young and old animals, and recognized cardiovascular health as a principal
determinant of lifespan. We and others have established that hypothalamic neurons sense the changing
peripheral milieu and also send out signals to control complex behaviors and organ system and peripheral
tissue functions. Our preliminary data and the work of others identified the same hypothalamic circuits to
control the aging process. For example, we found that neurons of the hypothalamus that control hunger have
significant impact on survival and lifespan. We also identified that these neurons mediate the action of
peripheral hormones implicated in the lifespan extending impact of calorie restriction. We hypothesize, that
action of circulating geronic substances on age related central and peripheral processes are mediated, at least
in part, by the hypothalamus. We will interrogate this question using mouse models in Specific Aim 1. We
will analyze complex behaviors, cardiac, muscle, bone and immune functions in control and experimental
animals, including animals with different age and genotype in a state of parabiosis. From a translational
perspective, it is crucial that the presence and relevance of geronic peptides are confirmed in higher species
such as primates, including humans. In an effort to address this issue, we have analyzed plasma from young
and aged nonhuman primates. Proteomics analysis identified candidate molecules in primates that have not
been identified in mice. In Specific Aim 2, we propose to utilize our newly established, high throughput in vitro
system to assess the cellular effects of putative geronic targets identified in our screen using nonhuman
primate fibroblasts. We will focus on intracellular events that are associated with aging cells. In Specific Aim
3, we will test primates to evaluate anti- and pro-geronic interventions on CNS and cardiovascular systems.
We will analyze the effects of young and aged plasma treatment of animals, known anti- and pro-geronic
peptides and those newly defined by in vivo analyses on cognitive brain functions of young, middle aged and
old nonhuman primates. Overall, execution of our aims will deliver new insights regarding the mechanisms of
action of geronic substances, new circulating geronic molecules and exploit robust test systems that will lend
themselves for collaborative work with other projects and investigators and the advance of defined biology to
clinically relevant application.
与衰老相关的晚发性慢性疾病,包括心血管疾病、阿尔茨海默病和
项目成果
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{{ truncateString('TAMAS L HORVATH', 18)}}的其他基金
The role of mitochondrial dynamics in diet-influenced regulation of food intake and adiposity
线粒体动力学在饮食影响的食物摄入和肥胖调节中的作用
- 批准号:
10154482 - 财政年份:2021
- 资助金额:
$ 53.6万 - 项目类别:
The role of mitochondrial dynamics in diet-influenced regulation of food intake and adiposity
线粒体动力学在饮食影响的食物摄入和肥胖调节中的作用
- 批准号:
10352446 - 财政年份:2021
- 资助金额:
$ 53.6万 - 项目类别:
The role of mitochondrial dynamics in diet-influenced regulation of food intake and adiposity
线粒体动力学在饮食影响的食物摄入和肥胖调节中的作用
- 批准号:
10520062 - 财政年份:2021
- 资助金额:
$ 53.6万 - 项目类别:
Hypothalamus-driven anti-aging processes impact murine models of Alzheimer's Disease
下丘脑驱动的抗衰老过程影响阿尔茨海默氏病小鼠模型
- 批准号:
10374026 - 财政年份:2020
- 资助金额:
$ 53.6万 - 项目类别:
Hypothalamus-driven anti-aging processes impact murine models of Alzheimer's Disease
下丘脑驱动的抗衰老过程影响阿尔茨海默氏病小鼠模型
- 批准号:
10582631 - 财政年份:2020
- 资助金额:
$ 53.6万 - 项目类别:
AgRP neurons promote the effects of calorie restriction on lifespan
AgRP 神经元促进热量限制对寿命的影响
- 批准号:
9263491 - 财政年份:2017
- 资助金额:
$ 53.6万 - 项目类别:
In vivo and in vitro systems to validate geronic proteins and their mechanisms of action
用于验证老年蛋白及其作用机制的体内和体外系统
- 批准号:
9264636 - 财政年份:2016
- 资助金额:
$ 53.6万 - 项目类别:
AgRP neurons regulate bone remodeling in aging
AgRP 神经元调节衰老过程中的骨重塑
- 批准号:
8321998 - 财政年份:2011
- 资助金额:
$ 53.6万 - 项目类别:
AgRP neurons regulate bone remodeling in aging
AgRP 神经元调节衰老过程中的骨重塑
- 批准号:
8688867 - 财政年份:2011
- 资助金额:
$ 53.6万 - 项目类别:
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