Neural mechanisms of dynapenia

项目摘要 随意肌力的丧失使老年人的功能限制增加4倍， 死亡率上升。几十年来，衰老中力量的丧失在很大程度上归因于 肌肉质量.然而，最近的研究结果清楚地表明，肌肉大小起着相对较小的作用， 我们的初步数据表明，身体虚弱的老年人激活的肌肉占总肌肉的比例要小得多， 在最大强度的任务中，与年龄匹配的更强的对手相比。尽管 随着年龄的增长，保持体力的重要性，几乎所有关于这一主题的研究都集中在 专门用于维持肌肉质量，关于虚弱的神经机制知之甚少。 我们假设，动力型老年人主动（神经）激活骨骼肌的能力下降， 由于皮质内抑制增加，肌肉最大程度地减少。为了验证我们的假设，我们将进行病例对照研究。 关于动力性的研究（即，弱）和非动力性老年人（n=50/组; >65岁）。此外，动力学 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，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 是为了确定是否dynapenic老年人表现出不同的膝伸肌自愿激活（VA）， 与非动力型老年人相比。第二是确定动力型老年人是否表现出差异 四头肌皮质内兴奋性（通过双脉冲经颅磁刺激评估） 与非动力性老年人相比， 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诱导的皮质内兴奋性 动态个体MI的强烈肌肉收缩已被证明可以提高力量和VA。URE 训练还显示出在训练和未训练的肢体中增强力量和VA。我们将使用 这些干预措施作为操作，以提高力量和VA。这将使我们能够更好地阐明 皮质内兴奋性的机制作用，通过检查相应的 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，通过核磁共振检查肌肉大小， 肌肉疲劳、白色物质高强度、身体活动、电刺激收缩特性， 与锻炼相关的身体表现、特征和状态测量等）。拟议的工作将提供 证据表明，老年人的虚弱与VA的损伤有关，并将提供关于 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发展， 改善老年人身体虚弱和增强身体机能的战略。

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.