Effects of 12-weeks of High-intensity Resistance Aerobic Circuit Exercise Training on Epigenetic Aging and Inflammation in Older HIV-infected Veterans
12 周高强度阻力有氧循环运动训练对老年 HIV 感染退伍军人表观遗传衰老和炎症的影响
基本信息
- 批准号:10710375
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-10-01 至 2024-09-30
- 项目状态:已结题
- 来源:
- 关键词:11 year oldAccelerationAcuteAddressAdultAerobicAerobic ExerciseAffectAgeAge YearsAgingAnaerobic ThresholdAnti-Inflammatory AgentsAttenuatedBaltimoreBenchmarkingBiological AgingBiological MarkersCandidate Disease GeneCardiovascular DiseasesCardiovascular systemCaringChronic DiseaseChronologyClinicalCohort StudiesControl GroupsCost SavingsDNADNA MethylationDataDiseaseEducational InterventionElderlyElementsEncapsulatedEpigenetic ProcessEquipmentEuropeanEventExerciseExercise TestGasesGenesGenetic TranscriptionGoalsHIVHIV InfectionsHealth PersonnelHospitalizationIL18 geneIndividualInflammationInflammatoryInflammatory ResponseInfrastructureInstitutionalizationInterleukin-6KnowledgeLeukocytesLinkMeasuresMediatingMedical centerMethylationMolecularMuscleObservational StudyOutcomePatternPharmaceutical PreparationsPhenotypePhysical activityPlayPopulation HeterogeneityProcessProviderQuality of lifeRandomizedReproducibilityResearchResistanceResourcesRiskRoleSiteSmokingTeleconferencesTestingTissuesTrainingTranscriptional RegulationUnited StatesVeteransVeterans Health AdministrationWorkage effectage relatedanti agingantiretroviral therapybehavior changecardiorespiratory fitnesscomorbiditycomparison controlcostcytokinedesigndisabilitydisability riskepigenetic markerexercise intensityexercise interventionexercise prescriptionexercise programexercise rehabilitationexercise trainingexperiencefitnessfrailtyimprovedindexinginnovationlifestyle factorsmethylation patternnovelpatient populationphysical inactivitypre-clinicalprecision medicinepreservationpreventprogramsprotein expressionresistance exercisesarcopeniasedentarystandard of caresuccesssystemic inflammatory responsetelehealthworking group
项目摘要
The Veterans Health Administration (VHA) is the largest U.S. HIV health provider with 64% of these
Veterans 50+ years of age. HIV infection in the setting of antiretroviral therapy represents a chronic disease
with an advanced aging phenotype manifested as increased cardiovascular disease, sarcopenia, and frailty,
primarily driven by systemic inflammation. We found a 42% reduction in VO2peak in older HIV+ adults that
significantly improved with high-intensity aerobic (AEX) and resistance training (RT). Yet, durable strategies for
high-intensity exercise in older adults remain a challenge and limited data are available in older HIV+ adults.
There is an urgent need to address these knowledge gaps in order to prevent widespread disability in HIV+
Veterans. Our objective is to provide a high-intensity exercise program for older Veterans that can be widely
disseminated and attenuates processes underlying aging. Epigenetic changes with increased age encapsulate
the putative effects of biological aging and lifestyle factors. DNA methylation (DNAm) patterns are frequently
modified in genes encoding pro-inflammatory cytokines, but can be reversed with exercise training. DNA
methylation age (DNAm Age) is an epigenetic biomarker that is expressed in years and provides a concrete
benchmark of advanced aging. We found that HIV+ adults have DNAm Age 11 years greater than age-
matched adults without HIV. Further, in adults without HIV, increased DNAm Age is associated with physical
inactivity, weakness and frailty. Our preliminary data in the Veterans Aging Cohort Study (VACS) show that
DNAm Age correlates with the VACS Index, a measure of frailty in HIV+ adults. However, the impact of
exercise training on DNAm Age has yet to be determined in any patient population. We propose to adapt our
center-based high-intensity AEX+RT intervention in older HIV+ Veterans into a video telehealth (VTEL)
delivered functional (no stationary equipment) exercise program that leverages epigenetic outcomes to
demonstrate anti-aging effects of exercise. The overarching hypothesis is that VTEL high-intensity
functional circuit exercise in older HIV+ Veterans will improve the advanced aging phenotype and
attenuate DNAm epigenetic processes underlying aging. Our experimental approach includes a 12-week
VTEL exercise intervention in 80 older HIV+ Veterans who are randomized to exercise or standard of care
sedentary control groups. AIM 1 will determine the effect of VTEL exercise on VO2peak, sarcopenia, and frailty
as phenotypic outcomes of advanced aging in HIV. AIM 2 will investigate the effect of VTEL exercise on DNAm
Age as a biomarker of advanced aging. AIM 3 will determine the effect of VTEL exercise on DNA methylation
of specific genes encoding specific pro-inflammatory cytokines in leukocytes. This approach will advance our
understanding of effective and feasible exercise strategies to prevent and minimize disability in patient
populations with advanced aging. Findings will provide an innovative approach to functional exercise in all
older adults. DNAm Age could be used as a personalized benchmark for an individual’s benefit from exercise
to promote sustainable behavior change. Findings will also provide epigenetic risk profiles that can be used to
generate a personalized exercise prescription, an important next step in the next decade of precision medicine.
The proposal leverages our exercise training experience in HIV and VTEL, availability of 3,000 HIV+ Veterans
at Atlanta and Baltimore VAMCs, and the VHA VTEL infrastructure. The capacity to disseminate VTEL
exercise with minimal cost using existing infrastructure will facilitate large-scale dissemination and national
impact. Deliverables include improved clinical outcomes and substantial cost savings from reduced
hospitalization and institutionalization rates.
退伍军人健康管理局(VHA)是美国最大的艾滋病医疗服务机构,拥有64%的艾滋病患者
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)
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Vincent Charles Marconi其他文献
Vincent Charles Marconi的其他文献
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{{ truncateString('Vincent Charles Marconi', 18)}}的其他基金
Host Genetic and Epigenetic Factors of the Progression, Comorbidities and Outcomes of Viral Infection
病毒感染进展、合并症和结果的宿主遗传和表观遗传因素
- 批准号:
10485494 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Multi-omic Predictors of Renal Function among HIV-infected Individuals of African Ancestry
非洲血统 HIV 感染者肾功能的多组学预测因子
- 批准号:
10222667 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Multi-omic Predictors of Renal Function among HIV-infected Individuals of African Ancestry
非洲血统 HIV 感染者肾功能的多组学预测因子
- 批准号:
10013809 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Multi-omic Predictors of Renal Function among HIV-infected Individuals of African Ancestry
非洲血统 HIV 感染者肾功能的多组学预测因子
- 批准号:
10862088 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Multi-omic Predictors of Renal Function among HIV-infected Individuals of African Ancestry
非洲血统 HIV 感染者肾功能的多组学预测因子
- 批准号:
10360539 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Multi-omic Predictors of Renal Function among HIV-infected Individuals of African Ancestry
非洲血统 HIV 感染者肾功能的多组学预测因子
- 批准号:
10610370 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Multi-omic Predictors of Renal Function among HIV-infected Individuals of African Ancestry
非洲血统 HIV 感染者肾功能的多组学预测因子
- 批准号:
10818685 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Effects of 12-weeks of High-intensity Resistance Aerobic Circuit Exercise Training on Epigenetic Aging and Inflammation in Older HIV-infected Veterans
12 周高强度阻力有氧循环运动训练对老年 HIV 感染退伍军人表观遗传衰老和炎症的影响
- 批准号:
10382206 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Effects of 12-weeks of High-intensity Resistance Aerobic Circuit Exercise Training on Epigenetic Aging and Inflammation in Older HIV-infected Veterans
12 周高强度阻力有氧循环运动训练对老年 HIV 感染退伍军人表观遗传衰老和炎症的影响
- 批准号:
10049196 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Central memory CD4 T cell infection: key role in ART response and HIV persistence
中央记忆 CD4 T 细胞感染:ART 反应和 HIV 持续存在的关键作用
- 批准号:
8738608 - 财政年份:2013
- 资助金额:
-- - 项目类别:
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