Neural mechanisms of dynapenia

描述(申请人提供)：自发性肌肉力量的丧失使老年人的功能受限增加4倍，死亡率增加2倍。几十年来，衰老导致的力量丧失在很大程度上归因于肌肉质量的丧失。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，我们的初步数据表明，与年龄匹配的强壮老年人相比，虚弱的老年人在最大强度任务中激活的肌肉占总肌肉的比例要小得多。尽管在衰老过程中保持体力很重要，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。我们假设，由于皮质内抑制的增加，发育迟缓的老年人自愿(神经学上)最大限度激活骨骼肌的能力降低。为了验证我们的假设，我们将对发育迟缓(即虚弱)和非发育迟缓的老年人(n=50/组；65岁)进行病例对照研究。此外，发育迟缓的个体将被随机分配到两种干预措施(运动想象(MI)或单侧阻力运动(URE)训练)中的一种，以提供增加力量和VA的实验操作，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。第一个是确定发育迟缓的老年人与非发育迟缓的老年人在膝关节伸肌自愿激活(VA)方面是否表现出差异。第二项是确定发育迟缓的老年人与非发育迟缓的老年人相比，股四头肌皮质内兴奋性(通过成对脉冲经颅磁刺激评估)是否存在差异，并检查皮质内兴奋性与VA之间的相关性。最后确定运动表象训练和单侧阻力运动训练引起的体力、VA和皮质内兴奋性变化之间的关系。肌肉强烈收缩的MI已被证明可以增强力量和视力。URE训练也被证明可以提高训练者和未训练者四肢的力量和视力。我们将利用这些干预手段来增强力量和视力。这将使我们能够通过检查各自结果之间的关联/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测量的肌肉大小、肌肉疲劳、脑白质高强度、体力活动、电刺激的收缩特性、体能表现、与运动相关的特征和状态测量等)。这项拟议的工作将提供证据，证明老年人的虚弱与VA的损害有关，并将为这种损害的神经机制提供洞察力。总而言之，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。

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.