Neural mechanisms of dynapenia

缺乏缺乏的神经机制

• 批准号: 8917835
• 负责人: Brian C Clark
• 金额: $ 34.73万
• 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/8917835
• 关键词: Address; Age; Aging; Case-Control Studies; Coin; Comorbidity; Data; Development; Elderly; Exercise; Exhibits; Gender; Greek; Health; 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; Physical Function; Physical Performance; Physical activity; Physically Handicapped; Physiologic pulse; Physiological; Play; Poverty; Property; Public Health; Randomized; Research; Resistance; Risk; Risk Factors; Role; Skeletal Muscle; Techniques; Testing; Training; Transcranial magnetic stimulation; Translations; White Matter Hyperintensity; Work; base; exercise training; inflammatory marker; insight; mortality; muscle form; muscle strength; neuromechanism; neurophysiology; quadriceps muscle; reduced muscle strength; sarcopenia; trait; white matter

DESCRIPTION (provided by applicant): 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 hyper intensity, 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.

描述（由申请人提供）：随意肌力量的丧失会使老年人的功能限制增加 4 倍，死亡率增加 2 倍。几十年来，衰老过程中力量的丧失很大程度上归因于肌肉质量的损失。然而，最近的研究结果清楚地表明，肌肉大小所起的作用相对较小，而且我们的初步数据表明，与年龄匹配的强壮老年人相比，体弱的老年人在最大力量任务中激活的总肌肉比例要小得多。尽管在衰老过程中保持体力具有重要意义，但几乎所有有关该主题的研究都只集中于保持肌肉质量，而对于无力的神经机制知之甚少。我们假设，由于皮质内抑制增加，无活力的老年人最大限度地自愿（神经）激活骨骼肌的能力下降。为了检验我们的假设，我们将对断绝症（即虚弱）和非断绝症老年人（n = 50/组；> 65 岁）进行病例对照研究。此外，无活力个体将被随机分配接受两种干预措施之一（运动想象（MI）或单侧阻力运动（URE）训练），以提供实验操作来增加力量和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。第一个是确定与非缺氧老年人相比，缺氧老年人在膝关节伸肌自主激活（VA）方面是否表现出差异。第二个目的是确定与非乏力老年人相比，乏力老年人股四头肌皮质内兴奋性（通过配对脉冲经颅磁刺激评估）是否表现出差异，并检查皮质内兴奋性测量与VA之间的关联。最后是确定无源个体运动想象训练和单侧阻力运动训练引起的力量、VA 和皮质内兴奋性变化之间的关联。强烈肌肉收缩的 MI 已被证明可以增强力量和 VA。 URE 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来增强力量和VA。这将使我们能够通过检查各个结果之间的关联/分离来更好地阐明皮质内兴奋性的机制作用。虽然本身不​​是具体目标的一部分，但我们将获得一些额外的结果来描述参与者的特征，作为协变量，并用于二次分析（例如，通过 MRI 获得的肌肉大小、肌肉疲劳、白质高强度、体力活动、电刺激收缩特性、身体表现、与运动相关的特征和状态测量等）。拟议的工作将提供证据证明老年人的虚弱与视力损伤有关，并将提供有关这种损伤的神经机制的见解。总的来说，这些知识将指导制定有针对性的策略，以改善老年人的虚弱和增强身体机能。