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: 9104073
• 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 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9104073
• 关键词: Accelerometer; 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 speed; 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; 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; Reporting; Research; Rest; Risk; Role; Serum; Site; Smoking; Time; United States; Viral Load result; Walking; Work; age related; aged; antiretroviral therapy; base; co-infection; combat; cost; design; disability; frailty; functional decline; high risk; improved; improved functioning; inflammatory marker; insight; lean body mass; men; metabolic rate; 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：据估计，美国 31% 的 HIV 感染者 (HIV+) 年龄在 50 岁或以上。即使在有效的抗逆转录病毒治疗后，这些人也面临着更高的功能衰退风险，因为生理机制会导致炎症增加和身体成分改变。随着时间的推移，这可能会导致新陈代谢率持续升高，日常体力活动的可用能量减少，因为需要更大比例的能量来对抗共病和修复细胞损伤。最近的证据表明，在年龄较大、适应力较差的人群中，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 感染人群功能衰退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、行走能量消耗和客观测量的体力活动。我们假设：(i) 与 HIV 阳性男性相比，HIV 阳性男性的步态速度较慢，并且随着年龄的增长下降得更快，(ii) 与 HIV 阳性男性相比，HIV 阳性男性在休息和标准步行时的能量消耗（氧气消耗和二氧化碳产生）都会升高，(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症标记物（例如 IL-6）介导。 和较低的瘦体重，(iv) HIV+男性将表现出比 HIV-男性更低的累积每日体力活动，并且疲劳驱动的活动模式的证据更明显；(v) HIV+男性相对于 HIV-男性，活动昼夜节律的日常变异性和复杂性更低。输出：本研究获得的数据将为以下方面提供重要见解：(i) 接受治疗的 HIV 感染者独立生活所需的多余能量，以及 (ii) 对身体活动和功能活动能力的相关威胁。我们将使用这些数据作为未来 R01 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，以及 (ii) 为旨在以下目的的干预措施提供证据：(a) 通过康复治疗改善身体成分和/或改变药物治疗方案以降低炎症来降低能量成本，从而提高步行效率，以及 (b) 增加体力活动并减少 通过分析昼夜节律活动模式，瞄准日常活动的低点来消除疲劳。这将有助于改善艾滋病毒老龄人口的功能并降低虚弱、残疾和死亡的风险。