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: 8911758
• 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 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8911758
• 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; 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; 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：美国估计有31%的艾滋病毒感染者(HIV+)年龄在50岁或以上。即使在有效的抗逆转录病毒治疗之后，由于导致炎症增加和身体成分改变的生理机制，这些人也面临着功能下降的高风险。随着时间的推移，这可能会导致代谢率持续上升，日常体力活动所需的能量减少，因为需要更多的能量来对抗并存的情况和修复细胞损伤。最近的证据表明，在年龄较大、韧性较差的人群中，这可能会加速脆弱、残疾和死亡的发生。方法在巴尔的摩多中心艾滋病队列研究(MACS)中，为了评估和量化老年HIV感染人群中功能衰退的加速发病和时间动力学，我们建议评估在巴尔的摩多中心艾滋病队列研究(MACS)中被病毒抑制的HIV+和HIV男性的步速、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)HIV+男性的步态速度将比HIV-男性更慢，并且随着年龄的增长将下降得更快，(Ii)相对于HIV-男性，HIV+男性在休息和标准步行时的能量消耗(O2消耗和二氧化碳产生)都将增加，(Iii)更高的能量消耗和更慢的步态速度之间的关联将通过更高水平的炎症标记物(例如，IL-6)和更低的瘦体重来调节，(Iv)HIV+男性将表现出更低的每日累积体力活动，比HIV-男性表现出更明显的疲劳驱动活动模式，(V)与艾滋病毒携带者相比，艾滋病毒携带者的日常活动的变异性和昼夜节律的复杂性更低。输出：从这项研究获得的数据将为以下方面提供关键的见解：(I)接受治疗的艾滋病毒感染者独立生活所需的过剩能量的数量，以及(Ii)对身体活动和功能活动的相关威胁。我们将以这些数据为基础，提交未来的R01报告，该报告旨在：(I)纵向评估作为功能健康状况因果生物标志物的休息和步行时的能量消耗，并(Ii)为旨在以下目的的干预措施提供证据：(A)通过康复治疗降低能量成本以提高步行效率，以改善身体成分和/或改变药物方案以降低炎症，以及(B)通过分析循环素活动模式来瞄准日常活动的低点来增加体力活动和减少疲劳。这将有助于改善老年艾滋病毒人群的功能，降低脆弱、残疾和死亡的风险。