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
• 负责人: Vincent Charles Marconi
• 金额: --
• 依托单位: SALEM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10049196
• 关键词: 11 year old; Acute; Address; Adult; Aerobic; Affect; Age; Age-Years; Aging; Anaerobic Threshold; Anti-Inflammatory Agents; Attenuated; Baltimore; Benchmarking; Biological Aging; Biological Markers; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Caring; Chronic Disease; Chronology; Clinical; Cohort Studies; Control Groups; Cost Savings; DNA; DNA Methylation; Data; Disease; Educational Intervention; Elderly; Elements; Encapsulated; Epigenetic Process; Equipment; European; Event; Exercise; Exercise Test; Gases; Genes; Genetic Transcription; Goals; HIV; HIV Infections; Health Personnel; Hospitalization; Individual; Inflammation; Inflammatory; Inflammatory Response; Infrastructure; Institutionalization; Interleukin-18; Interleukin-6; Knowledge; Leukocytes; Life; Link; Measures; Mediating; Medical center; Methylation; Molecular; Muscle; Observational Study; Outcome; Pattern; Pharmaceutical Preparations; Phenotype; Physical activity; Play; Population Heterogeneity; Process; Provider; Quality of life; Randomized; Reproducibility; Research; Resistance; Resources; Risk; Role; Site; Smoking; Testing; Tissues; Training; Transcriptional Regulation; United States; Veterans; Veterans Health Administration; Work; age effect; age related; anti aging; antiretroviral therapy; base; behavior change; cardiorespiratory fitness; comorbidity; cost; cytokine; design; disability; disability risk; epigenetic marker; exercise intensity; exercise intervention; exercise prescription; exercise program; exercise rehabilitation; exercise training; experience; fitness; frailty; improved; indexing; innovation; lifestyle factors; methylation pattern; novel; patient population; physical inactivity; pre-clinical; precision medicine; preservation; prevent; programs; protein expression; sarcopenia; sedentary; standard of care; strength training; success; systemic inflammatory response; telehealth; working group

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