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The Energetic Pathway to Disability in Older Persons

老年人致残的能量途径

基本信息

批准号：
8736674
负责人：
Luigi Ferrucci
金额：
$ 26.46万
依托单位：
NATIONAL INSTITUTE ON AGING
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

We propose that change in walking speed in older individuals is induced by feelings of fatigue that occur with exercise effort and that slowing down is a compensatory strategy to reduce the level of effort and avoid fatigue. The higher the metabolic rate required for a given amount of work, the more likely an individual may approach their maximum energetic availability. Metabolic requirements for a given activity or workload derive from two sources: a. Resting metabolic rate (RMR), the energy required to maintain homeostatic equilibrium at rest and in euthermic conditions; and b. Movement efficiency, the amount of energy required to perform one unit of work. There is emerging evidence that RMR declines with age in healthy individuals, but does not decline, or perhaps even increases, in older individuals who are sick or frail. Analogously, movement efficiency tends to decline with age, a change explained only in part by changes in body composition. Thus, with aging persons may require more energy to perform their usual activities. This increasing demand coupled with declining maximal aerobic capacity may explain why older persons perceive more fatigue than younger persons when doing the same tasks. In addition, the perception of fatigue, given the same ratio between energy availability/energy utilization may be modulated by several factors including inflammation, neurologic and other conditions related to "sickness behavior". We hypothesize that the lower fatigue threshold observed with increasing age and in frail older persons is due to: - increased RMR due to high cost of homeostasis and dysregulation or malfunction of the homeostatic network due to both acute and chronic disease processes; - increased energetic cost of mobility due to increased biomechanical inefficiency and decline in anatomical integrity and harmonic function; - compromised energy availability, due to specific pathological processes, such as congestive heart failure, and/or inefficient transport of energy to the required sites, mainly due to reduced homeostatic ability. To test the hypotheses that the energetic cost of walking, elevated RMR and development of fatigue at low levels of activity are key predictors of disability, we propose to explore relationships among RMR, the energetic and mechanical aspects of walking using gait lab studies and the threshold for development of fatigue using participants in the BLSA. The primary focus is to evaluate whether higher RMR, high energetic cost of walking, maximum oxygen consumption during peak exercise and dysregulation of the energy homeostatic network (level of inflammatory markers and hormones) independently predict energetic threshold for the development of subjective fatigue. A secondary objective is to verify whether information on RMR, energetic cost of walking, maximum oxygen consumption during peak exercise and dysregulation of the energy homeostatic network provide information on fitness and fatigability independent of the measure of fitness provided by a standard treadmill test. Participants consist of all BLSA participants. No exclusion criteria are established a priori. Measures include oxygen consumption at rest, during normal walking and prolonged walking (400 m) using portable equipment. Oxygen consumption and level of fatigue experienced using the Borg scale will be assessed while walking at a slow pace (0.67 m/s) on the treadmill for 5 minutes and during maximal exertional threshold testing. All measures associated with energetic cost and consumption related to the energetic pathway have been implemented in the BLSA: We have introduced measures of objective and subjective fatigue using the Borg Scale and the RQ ratio, respectively. In addition, we will be measuring metabolic rate using portable equipment in different conditions, including rest, customary walking, treadmill at low load and maximum load. Part of the study is to verify the hypothesis that change in the circulating level of hormones, inflammatory markers, markers of oxidative stress and autonomic function modulates the relationship between workload, energy consumption and the development of fatigue. Finally, we have introduced in the BLSA measures of metabolic consumption during daily activity, asking participants to wear an accelerometer combined with a heart rate recorded for seven days after leaving the clinic. Using individual calibration equations elaborated during their stay in the BLSA, we plan to estimate usual daily activity and to correlate it with our measures of efficiency and energetics. A symposium highlighting key findings from this work was given at the 2012 annual meeting of the Gerontological Society of America and a second symposium focusing on longitudinal data has been accepted for presentation at the 2013 meeting.

我们认为，老年人步行速度的变化是由锻炼时产生的疲劳感引起的，放慢速度是降低努力水平和避免疲劳的一种补偿策略。给定工作量所需的代谢率越高，个体就越有可能接近其最大能量利用率。特定活动或工作量的代谢需求来自两个来源：a.静息代谢率(RMR)，即在静止和低温条件下维持体内平衡所需的能量；b.运动效率，即完成一个工作单位所需的能量。有新的证据表明，在健康的人中，RMR随着年龄的增长而下降，但在患病或虚弱的老年人中，RMR并没有下降，甚至可能增加。类似地，运动效率随着年龄的增长而下降，这种变化只能部分地用身体成分的变化来解释。因此，随着年龄的增长，人们可能需要更多的能量来执行他们的日常活动。这种需求的增加，加上最大有氧能力的下降，可能解释了为什么老年人在做同样的任务时比年轻人感觉到更多的疲劳。此外，在能量可获得性/能量利用率相同的情况下，疲劳的感觉可能会受到几个因素的调节，包括炎症、神经和其他与“疾病行为”相关的情况。我们假设，随着年龄的增长和虚弱的老年人出现较低的疲劳阈值是由于： -由于动态平衡的高昂成本以及急慢性疾病过程中动态平衡网络的失调或失灵，导致RMR增加； -由于生物力学效率低下以及解剖完整性和协调功能下降，活动的能量成本增加； -由于特定的病理过程，如充血性心力衰竭，和/或能量传输到所需部位的效率低下，主要由于体内平衡能力降低，能量供应受到影响。为了验证这样的假设，即步行的能量成本、RMR升高和低活动水平下疲劳的发展是残疾的关键预测因素，我们建议使用步态实验室研究来探索RMR、步行的能量和机械方面以及使用BLSA参与者发展疲劳的阈值之间的关系。主要的焦点是评估较高的RMR、步行的高能量成本、高峰运动时的最大耗氧量以及能量平衡网络的失调(炎症标志物和激素水平)是否独立地预测主观疲劳的能量阈值。第二个目标是验证关于RMR、步行的能量成本、高峰运动期间的最大耗氧量和能量平衡网络的失调的信息是否提供了独立于标准跑步机测试提供的健康和疲劳性的信息。参与者由所有BLSA参与者组成。没有先验的排除标准。测量方法包括休息时、正常步行时和使用便携式设备进行长时间步行(400米)时的耗氧量。在跑步机上慢速(0.67m/S)步行5分钟和进行最大负荷运动阈值测试时，将使用博格量表评估氧耗量和疲劳程度。与能源成本和与能源途径相关的消耗有关的所有措施都已在BLSA中实施：我们介绍了分别使用Borg量表和RQ比率来衡量客观和主观疲劳的方法。此外，我们将使用便携式设备测量不同条件下的代谢率，包括休息、习惯步行、低负荷和最大负荷时的跑步机。这项研究的一部分是为了验证这样一个假设，即激素、炎症标志物、氧化应激标志物和自主神经功能的循环水平变化调节了工作量、能量消耗和疲劳发展之间的关系。最后，我们在BLSA中引入了日常活动期间代谢消耗的衡量标准，要求参与者在离开诊所后佩戴加速计，并记录七天的心率。使用他们在BLSA逗留期间精心设计的个人校准方程，我们计划估计日常活动，并将其与我们的效率和能量测量相关联。在美国老年学会2012年年会上举行了一次专题讨论会，重点介绍了这项工作的主要结果，并同意在2013年会议上介绍第二次专题讨论会，重点是纵向数据。