METABOLIC AND MOLECULAR ASPECTS OF SARCOPENIA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 骨质疏松症是指随着年龄的增长而出现的骨骼肌蛋白质质量和功能的丧失。骨质疏松症损害运动功能，并与基质代谢紊乱和老年人生活质量下降有关。本章概述了几种与骨质疏松症相关的表型改变，并考虑了几种生理过程和分子水平的信号通路，这些生理学过程和分子水平的信号通路可能是失调的，参与了骨质疏松症的发病机制。其发病机制复杂，多因素综合作用。更好地了解潜在的机制将有助于确定潜在的治疗靶点，并导致更好的治疗石棺减少症。我们正在探索和开发基于质谱学的方法来识别、表征和量化老年人类肌肉和转基因小鼠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，我们建议发现新的蛋白质和蛋白形式(翻译后修饰)，可能更好地表征老年人骨骼肌减少和肌肉代谢性疾病的发病机制。

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.