Neural mechanisms of dynapenia

描述（由申请人提供）：随意肌力的丧失使老年人的功能限制增加4倍，死亡率增加2倍。几十年来，衰老中力量的丧失主要归因于肌肉质量的丧失。然而，最近的研究结果清楚地表明，肌肉的大小起着相对较小的作用，我们的初步数据表明，弱老年人在最大力量任务中激活的总肌肉的比例要小得多，而与年龄匹配的强壮老年人相比。尽管在衰老过程中保持体力的重要性，但几乎所有关于这一主题的研究都集中在保持肌肉质量上，而对虚弱的神经机制知之甚少。我们推测，由于皮质内抑制增加，动力型老年人主动（神经学）最大限度地激活骨骼肌的能力下降。为了验证我们的假设，我们将对动力性（即，弱）和非动力性老年人（n=50/组; >65岁）。此外，动态个体将被随机分配到两种干预措施之一（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。首先是确定是否dynapenic老年人表现出不同的膝伸肌自愿激活（VA）相比，非dynapenic老年人。第二个是确定是否dynapenic老人表现出不同的皮质内兴奋性（通过成对脉冲经颅磁刺激评估）的股四头肌相比，非dynapenic老人，并检查皮质内兴奋性和VA的措施之间的关联。最后是确定的力量，VA和皮质内兴奋性的变化之间的关联引起的运动想象训练和单侧阻力运动训练的dynapenic个人。MI的强烈肌肉收缩已被证明可以提高力量和VA。URE训练也被证明可以提高训练和未训练肢体的力量和VA。我们将使用这些干预措施作为提高力量和VA的操作。这将使我们能够更好地阐明皮质内兴奋性的机制作用，通过检查各自的结果之间的关联/分离。虽然不是特定目标本身的一部分，但我们将获得一些额外的结果来表征参与者，作为协变量，并用于二次分析（例如，通过MRI的肌肉尺寸、肌肉疲劳、白色物质超强度、身体活动、电刺激收缩特性、身体表现、与锻炼相关的特征和状态测量等）。拟议的工作将提供证据表明，在老年人的弱点是与VA的损害，并将提供这种损害的神经机制的见解。总的来说，这些知识将指导制定有针对性的战略，以改善老年人的弱点和增强身体功能。

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.