Energy Expenditure, Activity, and Aging With HIV:Effects on Functional Longevity

HIV 感染者的能量消耗、活动和衰老：对功能寿命的影响

• 批准号: 8790198
• 负责人: JENNIFER ANN SCHRACK
• 金额: $ 12.93万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8790198
• 关键词: Acquired Immunodeficiency Syndrome; Activities of Daily Living; Address; Age; Aging; Anti-Retroviral Agents; Arthritis; Baltimore; Basal metabolic rate; Biological Markers; Body Composition; CD4 Lymphocyte Count; Carbon Dioxide; Cessation of life; Chronic lung disease; Circadian Rhythms; Clinical; Cohort Studies; Comorbidity; Consumption; Data; Diabetes Mellitus; Education; Employment; Energy Metabolism; Exhibits; Fatigue; Fatty acid glycerol esters; Future; Gait; Goals; HIV; HIV Infections; Health; Health Status; Hepatitis B; Hepatitis C; Hyperlipidemia; Hypertension; Independent Living; Individual; Infection; Inflammation; Interleukin-6; Intervention; Kidney Diseases; Knowledge; Lead; Life; Life Expectancy; Liver diseases; Longevity; Measures; Mediating; Metabolic; Methods; Modeling; Movement; NIH Office of AIDS Research; Output; Participant; Pattern; Persons; Pharmaceutical Preparations; Physical Function; Physical activity; Physiological; Physiology; Population; Production; Public Health; Quality of life; Race; Regimen; Rehabilitation therapy; Relative (related person); Reporting; Research; Rest; Risk; Role; Serum; Site; Smoking; Speed; Time; United States; Viral Load result; Walking; Work; age related; aged; antiretroviral therapy; base; combat; cost; design; disability; frailty; functional decline; high risk; improved; improved functioning; inflammatory marker; insight; men; public health relevance; repaired; social; working group

DESCRIPTION (provided by applicant): Background: An estimated 31% of HIV-infected (HIV+) individuals in the United States are aged 50 or older. These individuals are at heightened risk of functional decline due to physiological mechanisms that contribute to increased inflammation and alterations in body composition even after effective antiretroviral treatment. Over time, this may contribute to persistently elevated metabolic rate and decreased availability of energy for daily physical activities, as a greater proportion of energy is needed to combat comorbid conditions and repair cellular damage. Recent evidence indicates that in the older, less resilient population, this may accelerate the onset of frailty, disability, and death. Methods To assess and quantify the accelerated onset and temporal dynamics of functional decline in the aging HIV-infected population, we propose to assess gait speed, resting metabolic rate, walking energy expenditure, and objectively measured physical activity in virologically suppressed HIV+ and HIV- men in the Baltimore Multicenter AIDS Cohort Study (MACS). We hypothesize that: (i) gait speed will be slower in HIV+ men and will decrease faster with age relative to HIV- men, (ii) energy expenditure at rest and during standard walking (O2 consumption and CO2 production) will both be elevated in HIV+ men relative to HIV- men, (iii) the association between higher energy expenditure and slower gait speed will be mediated by higher levels of inflammatory markers (e.g., IL-6) and lower lean mass, (iv) HIV+ men will exhibit lower cumulative daily physical activity with more pronounced evidence of fatigue-driven activity patterns than HIV- men, and (v) HIV+ men will have lower day-to-day variability and complexity of circadian rhythms of activity relative to HIV- men. Output: The data obtained from this research will provide critical insight into (i) the amount of excess energy needed for independent living in those with treated HIV infection, and (ii) the associated threats to physical activity an functional mobility. We will use these data as the basis for a future R01 submission designed to: (i) longitudinally evaluate energy expenditure at rest and during walking as causal biomarkers of functional health status and (ii) provide evidence for interventions aimed at: (a) increasing walking efficiency by lowering energy costs through rehabilitative therapy to improve body composition and/or altered drug regimens to lower inflammation, and (b) increasing physical activity and reducing fatigue by targeting low-points of daily activity through analysis of circadin activity patterns. This will contribute to improved function and reduced risk of frailty, disabilit, and death in aging HIV populations.

描述（由申请人提供）：背景：在美国，估计有31%的HIV感染（HIV+）个体年龄在50岁或以上。这些人由于生理机制导致功能下降的风险增加，即使在有效的抗逆转录病毒治疗后，这些生理机制也会导致炎症增加和身体成分改变。随着时间的推移，这可能导致代谢率持续升高，日常体力活动的能量可用性降低，因为需要更大比例的能量来对抗共病状况和修复细胞损伤。最近的证据表明，在老年人中，弹性较低的人群，这可能会加速虚弱，残疾和死亡的发生。方法为了评估和量化老年HIV感染人群中功能下降的加速发作和时间动态，我们建议在巴尔的摩多中心艾滋病队列研究（MACS）中评估病毒学抑制的HIV+和HIV-男性的步态速度、静息代谢率、步行能量消耗和客观测量的体力活动。我们假设：（i）相对于HIV-男性，HIV+男性的步态速度较慢，并且随着年龄的增长，步态速度下降较快，（ii）相对于HIV-男性，HIV+男性在休息时和标准行走过程中的能量消耗（O2消耗和CO2产生）都将升高，（iii）较高的能量消耗和较慢的步态速度之间的关联将由较高水平的炎性标志物（例如，IL-6）和较低的瘦体重，（iv）HIV+男性将表现出较低的累积每日身体活动，与HIV-男性相比，疲劳驱动的活动模式的证据更明显，和（v）HIV+男性相对于HIV-男性将具有较低的昼夜活动节律的每日变化性和复杂性。输出量：从这项研究中获得的数据将提供关键的洞察力（i）在接受治疗的艾滋病毒感染者中独立生活所需的多余能量的数量，以及（ii）对身体活动和功能移动性的相关威胁。我们将使用这些数据作为未来R 01提交的基础，旨在：（i）纵向评估休息和行走时的能量消耗，作为功能健康状态的因果生物标志物，（ii）为旨在：（a）通过康复治疗降低能量成本以提高行走效率，从而改善身体组成和/或改变药物方案以降低炎症，和（B）通过分析circadin活动模式以日常活动的低点为目标来增加身体活动和减少疲劳。这将有助于改善功能，降低老年艾滋病毒感染者脆弱、残疾和死亡的风险。