The Energetic Pathway to Disability in Older Persons

我们建议，在老年人的步行速度的变化是由疲劳的感觉，发生与运动的努力和放慢是一种补偿策略，以减少努力的水平，避免疲劳。 给定工作量所需的代谢率越高，个体越有可能接近其最大能量可用性。给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），即在静息和正常体温条件下维持体内平衡所需的能量;和B.运动效率，完成一个单位的工作所需的能量。 有新的证据表明，RMR随着健康个体的年龄而下降，但在生病或虚弱的老年人中不会下降，甚至可能增加。类似地，运动效率往往随着年龄的增长而下降，这种变化只能部分解释为身体成分的变化。因此，随着年龄的增长，人们可能需要更多的能量来进行他们的日常活动。 这种需求的增加加上最大有氧能力的下降，可以解释为什么老年人在做同样的任务时比年轻人感到更疲劳。此外，在能量可用性/能量利用率之间的比率相同的情况下，疲劳的感知可能受到几个因素的调节，包括炎症、神经学和与“疾病行为”相关的其他状况。 我们假设，随着年龄的增长和体弱的老年人观察到的较低的疲劳阈值是由于： - 由于急性和慢性疾病过程导致的稳态和稳态网络失调或功能障碍的高成本而增加的RMR; - 由于生物力学效率降低以及解剖完整性和协调功能下降，活动性的能量成本增加; - 由于特定的病理过程，例如充血性心力衰竭，和/或主要由于体内平衡能力降低，能量向所需部位的低效运输，损害能量可用性。 为了验证这一假设，即步行的能量成本，RMR升高和疲劳的发展在低水平的活动是残疾的关键预测因素，我们建议探索RMR之间的关系，步行的能量和机械方面的步态实验室研究和阈值疲劳的发展使用参与者在BLSA。 主要重点是评估是否较高的RMR，步行的高能量成本，在高峰运动期间的最大耗氧量和能量稳态网络（炎症标志物和激素水平）的失调独立预测主观疲劳的发展能量阈值。 第二个目的是验证RMR、步行的能量消耗、高峰运动期间的最大耗氧量和能量稳态网络失调的信息是否提供与标准跑步机测试提供的健身测量无关的健身和疲劳信息。 参与者包括BLSA的所有参与者。没有建立先验的排除标准。措施包括休息时、正常行走时和使用便携式设备长时间行走（400米）时的耗氧量。在跑步机上以慢速（0.67 m/s）行走5分钟和最大劳力阈值测试期间，使用博格量表评估耗氧量和疲劳水平。 BLSA已实施与能量途径相关的能量成本和消耗相关的所有措施： 我们已经分别使用博格量表和RQ比率介绍了客观和主观疲劳的测量。此外，我们将在不同条件下使用便携式设备测量代谢率，包括休息、习惯性步行、低负荷和最大负荷的跑步机。这项研究的一部分是为了验证这一假设，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的变化调节工作量，能量消耗和疲劳的发展之间的关系。 最后，我们在BLSA中引入了日常活动中代谢消耗的测量，要求参与者佩戴加速度计，并在离开诊所后记录7天的心率。使用在BLSA逗留期间制定的个人校准方程，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成果，并已接受在2013年会议上介绍第二次专题讨论会，重点是纵向数据。

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.