METABOLIC AND MOLECULAR ASPECTS OF SARCOPENIA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 肌肉减少症是指随着年龄的增长而发生的骨骼肌蛋白质质量和功能的丧失。肌肉减少症损害运动功能，并与基质代谢失调和老年人生活质量下降有关。本章概述了几个表型改变与肌肉减少症，并认为几个生理过程和分子水平的信号通路，可能是失调，参与肌肉减少症的发病机制。 其发病机制是复杂和多因素的。更好地了解潜在的机制将有助于确定潜在的治疗靶点，并导致更好的治疗肌肉减少症。我们正在探索和开发基于质谱的方法，用于识别，表征和量化老年人肌肉和转基因小鼠中的肌肉线粒体蛋白表达模式（蛋白质组）。通过与健康正常肌肉中线粒体蛋白表达模式的比较，我们提出发现新的蛋白质和蛋白质形式（翻译后修饰），可以更好地表征老年人肌肉减少症和肌肉代谢紊乱的发病机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sarcopenia refers to the loss of skeletal muscle protein mass and function that occurs with advancing age. Sarcopenia impairs motor function, and is associated with dysregulated substrate metabolism and reduced quality of life in the elderly. This chapter outlines several phenotypic alterations that are associated with sarcopenia, and considers several physiologic processes and molecular level signaling pathways that may be dysregulated and involved in the pathogenesis of sarcopenia. The pathogenesis is complex and multifactorial. A better understanding of the underlying mechanisms will help identify potential therapeutic targets, and lead to better treatments for sarcopenia. We are exploring and developing mass spectrometry-based approaches for identifying, characterizing, and quantifying muscle mitochondrial protein expression patterns (proteome) in elderly human muscle, and genetically modified mice. By comparison with mitochondrial protein expression patterns in healthy normal muscle, we propose to discover novel proteins and protein forms (post-translational modifications) that may better characterize the pathogenesis of sarcopenia and muscle-based metabolic disorders in the elderly.