Neural mechanisms of dynapenia

缺乏缺乏的神经机制

• 批准号: 8632154
• 负责人: Brian C Clark
• 金额: $ 34.88万
• 依托单位: OHIO UNIVERSITY ATHENS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632154
• 关键词: Address; Age; Aging; Case-Control Studies; Coin; Comorbidity; Data; Development; Elderly; Exercise; Exhibits; Gender; Greek; Imagery; Impairment; Individual; Intervention; Knee; Knowledge; Life; Limb structure; Magnetic Resonance Imaging; Measures; Minor; Mission; Modeling; Motor; Muscle; Muscle Contraction; Muscle Fatigue; Muscle Weakness; Outcome; Participant; Performance; Physical Function; Physical activity; Physiologic pulse; Physiological; Play; Poverty; Public Health; Randomized; Research; Resistance; Risk; Risk Factors; Role; Skeletal Muscle; Techniques; Testing; Training; Transcranial magnetic stimulation; Translations; White Matter Hyperintensity; Work; base; disability; inflammatory marker; insight; mortality; muscle form; muscle strength; neuromechanism; neurophysiology; physical property; public health relevance; quadriceps muscle; sarcopenia; trait; white matter

PROJECT SUMMARY A loss of voluntary muscle strength predisposes elders to a 4-fold increase in functional limitations and a 2-fold increase in mortality. For decades, the loss of strength in aging has been largely attributed to the loss of muscle mass. However, recent findings clearly demonstrate that muscle size plays a relatively minor role, and our preliminary data suggests that weak elders activate a substantially smaller proportion of their total muscle during a maximal strength task in comparison to their stronger age-matched counterparts. Despite the significance of maintaining physical strength in aging, virtually all of the research on this topic has focused exclusively on maintaining muscle mass, and little is known regarding the neural mechanisms of weakness. We hypothesize that dynapenic elders have a decreased ability to voluntarily (neurologically) activate skeletal muscle maximally due to increased intracortical inhibition. To test our hypothesis we will conduct a case-control study on dynapenic (i.e., weak) and non-dynapenic elders (n=50/group; >65 yrs). Additionally, the dynapenic individuals will be randomly assigned to one of two interventions (motor imagery (MI) or unilateral resistance exercise (URE) training) to provide an experimental manipulation to increase strength and VA, which will permit us to better elucidate physiological mechanisms. This project will address three specific aims. The first is to determine whether dynapenic elders exhibit differences in knee extensor voluntary activation (VA) in comparison to non-dynapenic elders. The second is to determine whether dynapenic elders exhibit differences in intracortical excitability (assessed via paired-pulse transcranial magnetic stimulation) of the quadriceps femoris muscles in comparison to non-dynapenic elders, and to examine the association between measures of intracortical excitability and VA. The last is to determine the association between the changes in strength, VA, and intracortical excitability induced by motor imagery training and unilateral resistance exercise training in dynapenic individuals. MI of strong muscle contractions has been shown to enhance strength and VA. URE training has also been shown to enhance strength and VA in both the trained and untrained limbs. We will use these interventions as manipulations to enhance strength and VA. This will allow us to better elucidate the mechanistic role of intracortical excitability by examining the association/disassociation between the respective outcomes. While not part of the specific aims per se, we will obtain a number of additional outcomes to characterize the participants, serve as covariates, and use for secondary analyses (e.g., muscle size via MRI, muscle fatigue, white matter hyperintensity, physical activity, electrically-stimulated contractile properties, physical performance, trait and state measures related to exercise, etc.). The proposed work will provide evidence that weakness in the elderly is associated with impairments in VA and will provide insight on the neural mechanisms of this impairment. Collectively, this knowledge will guide the development of targeted strategies to ameliorate weakness and enhance physical function in seniors.

项目总结 随意肌肉力量的丧失使老年人的功能受限增加4倍，功能障碍增加2倍 死亡率的增加。几十年来，衰老导致的体力丧失在很大程度上是由于 肌肉发达。然而，最近的发现清楚地表明，肌肉大小起到的作用相对较小，而且 我们的初步数据表明，虚弱的老年人激活的肌肉在他们总肌肉中的比例要小得多 在最大强度的任务中，与年龄匹配的更强壮的同龄人相比。尽管 保持体力在衰老中的意义，几乎所有关于这一主题的研究都集中在 仅限于维持肌肉质量，而对虚弱的神经机制知之甚少。 我们假设，营养不良的老年人自愿(神经学上)激活骨骼的能力降低。 最大程度的肌肉抑制是由于皮质内抑制增加。为了检验我们的假设，我们将进行病例对照 中老年(弱)和非中老年人(n=50/组；65岁)的研究。此外，更年期的 个人将被随机分配到两种干预措施中的一种(运动想象(MI)或单边抵抗 运动(URE)训练)提供实验性的手法以增加力量和视力，这将 使我们能够更好地阐明生理机制。该项目将针对三个具体目标。第一 目的是确定发育迟缓的老年人在膝关节伸肌自主激活(VA)方面是否存在差异 与没有更年期的长辈相比。第二是确定更年期的长辈是否表现出差异 在皮质内兴奋性(通过成对脉冲经颅磁刺激评估)股四头肌 股骨肌与无发育迟缓的老年人的比较，并检查测量之间的联系 皮质内兴奋性和VA。最后一项是确定力量，VA， 运动表象训练和单侧阻力运动训练诱发的皮层内兴奋性 发育迟缓的个体。肌肉强烈收缩的MI已被证明可以增强力量和视力。乌雷 训练也被证明可以增强训练者和未训练者四肢的力量和视力。我们将使用 这些干预措施可以作为增强力量和视力的手法。这将使我们能够更好地阐明 皮层内兴奋性的机制作用--通过检查大脑皮质内兴奋性之间的联系/分离 结果。虽然不是具体目标本身的一部分，但我们将获得一些额外的成果，以 表征参与者，充当协变量，并用于二次分析(例如，通过MRI的肌肉大小， 肌肉疲劳，白质高强度，体力活动，电刺激的收缩特性， 与运动有关的体能表现、特征和状态措施等)。拟议的工作将提供 有证据表明老年人的虚弱与VA的损害有关，这将为我们提供关于 这种损伤的神经机制。总而言之，这些知识将指导有针对性的 改善老年人虚弱和增强身体机能的策略。