The Energetic Pathway to Disability in Older Persons

具体目标 我们提出，步行能量成本的变化与导致老年人进行性功能衰退和残疾的因果路径有关。人类机器效率的下降，运动剩余能量的减少，优化能量产生的动态平衡机制的损害，最后，在低活动水平下疲劳的发展，可能构成导致久坐行为和进行性残疾的因果路径的要素。 根据我们的假设，相对于体力活动程度的过度疲劳可能来自不同的、但潜在的协同机制： -由于动态平衡的高成本和动态平衡网络的失调或失灵(由于急性和慢性病过程)，RMR增加； -由于生物力学效率低下以及“人类移动机器”的解剖完整性和协调功能下降，行动的能量成本增加； -由于特定的病理过程，例如充血性心力衰竭，和/或能量向所需部位的低效传输，主要由于体内平衡能力降低，能量供应受到影响。 研究计划 为了验证步行的高能量成本、增加的RMR和在低活动水平下疲劳的发展是残疾的关键预测因素这一假说，我们建议探索步行的能量和机械方面(步态实验室)和BLSA参与者的疲劳发展阈值之间的关系。 研究结果 主要结果：评估较高的RMR、步行的高能量成本和能量平衡网络的失调(炎症标志物和激素水平)是否是发展主观疲劳的能量阈值的独立预测因素。 次要结果：验证关于RMR、步行的能量成本和能量平衡网络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； 研究群体 参与者将由所有BLSA参与者组成。没有先验的排除标准。我们寻求常规测量休息、正常步行和长时间步行(400米)时的耗氧量。由于在正常测试期间已经使用了便携式设备，因此参与者的BLSA调度将不需要额外的时间。 疲劳阈值将使用博格量表进行估算。在体力任务期间，每个参与者都将按预定的间隔接受博格量表的测试。 实施BLSA以测试残疾的能量途径 我们在BLSA中引入了分别使用Borg等级和RQ比率来衡量客观和主观疲劳的方法。这种测量将在评估体能表现的任务期间定期进行。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、运动前、习惯步行、低负荷和最大负荷时的跑步机。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的变化调节了工作量、能量消耗和疲劳发展之间的关系。

SPECIFIC AIMS We proposed that changes in the energetic cost of walking is implicated in the causal pathway that leads to progressive functional decline and disability in older persons. The deterioration of efficiency of the human machine, the reduce availability of residual energy for movement, the impairment of the homeostatic mechanisms that optimize energy production and, finally, the development of fatigue at low levels of activity may constitute the elements of a causal pathway leading to sedentary behavior and progressive disability. According to our hypothesis, excessive fatigue relative to the degree of physical activity may arise from different, but potentially synergic mechanisms: - increased RMR due to high cost of homeostasis and dysregulation or malfunction of the homeostatic network (due to both acute and chronic diseases processes); - increased energetic cost of mobility due to increased biomechanical inefficiency and decline in the anatomical integrity and harmonic function of the "human ambulatory machine"; - compromised energy availability , due to specific pathological processes, CHF for instance, and/or inefficient transport of energy to the required sites, mainly due to reduced homeostatic ability. RESEARCH PLAN To test the hypothesis high energetic cost of walking, increased RMR and and development of fatigue at low levels of activity are key predictor of disability, we propose to explore the relationship between RMR, the energetic and mechanical aspects of walking (gait lab) and the threshold for the development of fatigue in the participants of the BLSA.. Outcomes of the study Primary outcome: to evaluate whether higher RMR, high energetic cost of walking, and a dysregulation of the energy homeostatic network (level of inflammatory markers and hormones) are independent predictors of energetic threshold for the development of subjective fatigue. Secondary outcome: to verify whether information on RMR, energetic cost of walking 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; Study population Participants will consist of all BLSA participants. No exclusion criteria are established a priori. We seek to routinely measure oxygen consumption at rest, during normal walking and prolonged walking (400 m). Since portable equipment is already used during the normal testing, no additional time will be required to the BLSA scheduling of the participants. Threshold of fatigue will be estimated using Borg Scale. Each participant will be administered the Borg Scale at predetermined intervals during the physical task. Implementation of the BLSA to test the energetic pathway of disability We have introduced in BLSA measures of objective and subjective fatigue using the Borg Scale and the RQ ratio, respectively. This measurements will be performed at regular intervals during the tasks evaluating physical performance. In addition, we will be measuring metabolic rate using a portable equipment in different conditions, including rest, pre-exercise, customary walking, treadmill at low load and maximum load. Part of the study is to verify the hypothesis that change 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.