Network models to capture multiple outcomes resulting from multi-component, salutogenic interventions
网络模型捕捉多成分有益干预措施产生的多种结果
基本信息
- 批准号:10721644
- 负责人:
- 金额:$ 15.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-04 至 2028-07-31
- 项目状态:未结题
- 来源:
- 关键词:8-hydroxy-2&apos-deoxyguanosineAffectAgeAge-associated memory impairmentAgingAnimalsAttenuatedBehavioralBiochemicalBloodBotanicalsC-reactive proteinCognitionCognitiveComplementary HealthComputer ModelsControl GroupsDataDevelopmentDiseaseDisease ProgressionExerciseFemaleFutureGenesGoalsGotu kolaGraphHealthHealth Care ResearchHealth PromotionHealth StatusHippocampusHumanImpaired cognitionIndividualInflammationInflammatoryIntegrative MedicineInterventionLaboratoriesLearningMeasurementMeasuresMediatingMemoryMethodologyMethodsModelingMolecularMolecular ProfilingMusMusculoskeletalOrganOrganismOutcomeOxidative StressPathogenesisPathway interactionsPersonal SatisfactionProcessRandomizedResearchRunningSystemSystems BiologyTestingTherapeutic InterventionTissuesTrainingWaterWhole Organismage relatedagedanimal tissuebody systemcareercognitive changecognitive enhancementcognitive functioncognitive taskdeep learning modeldesigndrinking waterdynamic systemexperienceexperimental studyglobal healthhealth dataimprovedinsightinterestmalemetabolomicsmodel buildingmodel organismmolecular domainmorris water mazemouse modelnetwork modelsprogramspromote resilienceresponserestorationsextranscriptomicswhole health
项目摘要
Project Summary
Health care research has extensively studied disease pathogenesis, but very little is known about the
complementary process of health restoration, or salutogenesis. Salutogenesis may involve the use of single or
multiple interventions. These may affect multiple targets to restore specific functions as well as affect whole
person health. This project aims to develop methods to study multisystem signatures of health restoration
obtained through multiple interventions both at the level of the organ and the whole organism. Currently, there
is considerable interest in identifying non-pharmaceutical interventions to improve resilience to cognitive
decline during aging. The proposed project will use a mouse model of age-related cognitive decline to study
molecular signatures and functional changes associated with restoration of healthy cognitive function. We will
evaluate two interventions that have previously been demonstrated to improve cognition in aged mice i.e.
exercise and a water extract (CAW) of the botanical Centella asiatica. Eighteen month old C57BL/6 male and
female mice will be randomized into an exercise group (voluntary access to a running wheel), a CAW group
(1000 mg/kg/day, administered in the drinking water), a group that receives both CAW and exercise, and a
control group that receives neither intervention each for a period of 35 days. Untreated male and female young
(4 month old) mice will serve as young controls. We will assess the impact of these two interventions,
separately and combined, on four health measures: cognition, global inflammatory status, global oxidative
stress and mobility using Morris Water Maze test, blood C-reactive protein, blood 8-hydroxydeoxyguanosine
and DigiGait respectively. At the conclusion of treatment, hippocampal tissue from the animals will be collected
and transcriptomics and metabolomics analysis will be performed. We will initially identify genes or metabolites
(singly or in clusters) that are significantly altered by the treatments. This -omics data will then be integrated
with the behavioral and blood data to create computational models that will be used to derive the unique
molecular signatures and health data associated with improved cognition. We will also explore whether the
molecular signature changes associated with cognitive improvement are a reversal of those seen in cognitive
decline (young vs old untreated animals), or represent a new salutogenic pathway. A heterogenous multi-level
network (HMLN) model will be used to describe and evaluate the correlations between all health outcomes
described here and the molecular data. Ultimately, similar HMLN models can be used as a basis to identify the
timing and types of interventions that are optimal for restoring cognitive health. The methodology developed in
these experiments can then be expanded beyond cognition to encompass other aspects of whole organism
health.
Template Version: 9/16/2021
Research Abstract Version: 1
项目总结
项目成果
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