Intramyocellular Biotransport and Muscle Quality in Aging and Obesity

[1236451]衰老和肥胖与瘦体质量减少和脂肪质量增加有关，两者都会导致力量和身体功能的下降。老年妇女特别容易残疾，因为与男性相比，她们有更多的脂肪量，更少的骨骼肌量和力量，更少的体力活动。采用非侵入性方法确定超重或肥胖老年人的健康状况，有助于通过饮食和运动进行干预。这个项目的动机是需要衡量这些干预措施的相对效益，以增加腿部肌肉质量，这是身体健康的衡量标准。最近的研究表明，磁共振成像（MRI）可以测量人体肌肉中定向水扩散和脂质浓度的局部特性。刚刚完成了一项对47名不同体重和健康水平的老年妇女大腿肌肉的系统研究，包括运动训练和肥胖亚组减肥后的随访研究。研究发现，整体健康状况与肌肉纤维内部水分输送的MRI测量结果之间存在很强的相关性。该项目的总体目标是通过模拟MRI编码信息的方式来解释这些结果，并应用这些模拟来了解肌纤维内代谢物的运输。人体肌肉是一个复杂的分层组织，因此这个项目的重点是一个多阶段的模型，可以适应与衰老和肥胖相关的肌肉结构变化。从获得的MRI数据开始，该模型将包括肌纤维内有序或无序的肌原纤维和脂质结构域阵列，并对水、某些代谢物和钙离子的多相运输进行数值模拟。然后，模型参数将被明智地改变，以研究与肌纤维内代谢受损相关的质量运输的各种情况。所提出的研究的关键目标是将数值模拟与非侵入性成像技术（如MRI）获得的数据相结合，这将提供对肌肉生理和代谢的见解，以前只有通过需要肌肉活检的侵入性技术才能获得。局部定向扩散和肌肉内脂质分布之间的联系还没有被探索，因为表面上这样的测量直到现在还不可能。目前生活在美国的8100万婴儿潮一代中，60岁以上的女性中有70%超重或肥胖。这个项目的变革性部分是使用当地诊所可用的MRI技术，将个人的身体健康与肌肉内部物质传输的物理特性联系起来。除了帮助计划临床干预，以防止残疾的发作，这个项目将提高科学知识的老化肌肉如何利用能量来源于脂质。从这项研究工作中获得的知识可以纳入经典的工程课程，或新的跨学科课程。未来还计划建立一个以肌肉和中枢神经系统转运现象为重点的NSF本科生研究经验（REU）项目。

1236451PI: GeorgiadisAging and obesity are associated with reductions in lean body mass and increases in fat mass, both leading to declines in strength and physical function. Elderly women are particularly prone to disability as they have more fat mass, less skeletal muscle mass and strength, and are less physically active compared to their male counterparts. Determining fitness for the elderly who are overweight or obese by using non-invasive means will facilitate intervention by diet and exercise. This project is motivated by the need to measure the relative benefits of these interventions to increase leg muscle quality, which is a measure of physical fitness. Recent research has demonstrated that Magnetic Resonance Imaging (MRI) can measure the local properties of directional water diffusion and lipid concentration in the human muscle. A systematic study of the thigh muscles of 47 elderly women differing in weight and fitness level has just been completed, including a follow-up study after exercise training and weight loss of the obese subgroup. Strong correlations were found between overall fitness and MRI measures related to transport of water inside the muscle fibers. The overarching aim of this project is to interpret these results by simulating the way MRI encodes information and applying these simulations to understand the transport of metabolites within the muscle fiber. Human muscle is a complex hierarchical tissue, so the focus of this project is on a multiphase model that can accommodate the muscle structural changes relevant to aging and obesity. Starting from the MRI data acquired, the model will include an ordered or disordered array of myofibrils and lipid domains inside the muscle fiber, and multiphase transport of water, certain metabolites, and calcium ions will be simulated numerically. The model parameters will then be altered judiciously to study various scenarios of mass transport related to impaired metabolism inside the muscle fiber. The key objective of the proposed research is the combination of numerical modeling with data obtained from non-invasive imaging techniques, such as MRI, which will offer insights into muscle physiology and metabolism previously only available from invasive techniques requiring muscle biopsy. The connection between local directional diffusion and the distribution of the lipids inside the muscle has not been explored, because ostensibly such measurements have not been possible until now.Among the 81 million baby boomers currently living in the US, 70% of women over 60 years of age are overweight or obese. The transformative part of this project is the use of MRI technology available in the local clinic to connect the physical fitness of the individual with the physics of mass transport inside the muscle. In addition to helping plan the clinical intervention in order to prevent the onset of disabilities, this project will improve scientific knowledge of how the aging muscle utilizes energy derived from lipids. Knowledge gained from this research effort can be incorporated into classical engineering courses, or new interdisciplinary courses. The future establishment of an NSF Research Experiences for Undergraduates (REU) program focusing on Transport Phenomena in Muscle and Central Nervous System is also planned.