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.

项目概要 随意肌力量的丧失会使老年人的功能限制增加 4 倍，并使老年人的能力增加 2 倍。 死亡率增加。几十年来，衰老过程中体力的丧失很大程度上归因于 肌肉质量。然而，最近的研究结果清楚地表明，肌肉大小的作用相对较小，并且 我们的初步数据表明，体弱的老年人激活其总肌肉的比例要小得多 在最大力量任务中与同龄的更强者进行比较。尽管 在衰老过程中保持体力的重要性，几乎所有关于这个主题的研究都集中在 专门针对维持肌肉质量，而对于无力的神经机制知之甚少。 我们假设缺乏活力的老年人自愿（神经）激活骨骼的能力下降 由于皮质内抑制增加而最大程度地增强肌肉。为了检验我们的假设，我们将进行病例对照 对乏力（即虚弱）和无乏力老年人（n=50/组；>65 岁）的研究。此外，无烯酮 个体将被随机分配接受两种干预措施之一（运动想象（MI）或单方面抵抗） 运动（URE）训练）提供实验操作以增加力量和VA，这将 使我们能够更好地阐明生理机制。该项目将实现三个具体目标。第一个 目的是确定无活力老年人在膝关节伸肌自主激活（VA）方面是否表现出差异 与非无动力缺乏的老年人进行比较。第二是确定无供血长者是否表现出差异 股四头肌的皮质内兴奋性（通过配对脉冲经颅磁刺激评估） 股骨肌肉与非缺乏性缺乏的老年人进行比较，并检查测量值之间的关联 皮质内兴奋性和 VA。最后是确定强度、VA、 运动想象训练和单侧抗阻运动训练引起的皮质内兴奋性 缺乏乏力的个体。强烈肌肉收缩的 MI 已被证明可以增强力量和 VA。尿素 训练也被证明可以增强受过训练和未经训练的四肢的力量和VA。我们将使用 这些干预措施作为增强力量和VA的操作。这将使我们能够更好地阐明 通过检查各自之间的关联/分离来了解皮质内兴奋性的机制作用 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 描述参与者的特征，作为协变量，并用于二次分析（例如，通过 MRI 测量肌肉大小， 肌肉疲劳、白质高信号、体力活动、电刺激收缩特性、 与运动相关的身体表现、特质和状态测量等）。拟议的工作将提供 有证据表明老年人的虚弱与 VA 损伤有关，并将提供有关 这种损伤的神经机制。总的来说，这些知识将指导有针对性的开发 改善老年人虚弱和增强身体机能的策略。