METABOLIC AND MOLECULAR ASPECTS OF SARCOPENIA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。骨骼肌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。骨骼肌减少症损害运动功能，并与底物代谢失调和老年人生活质量下降有关。本章概述了几种与肌少症相关的表型改变，并考虑了几种可能失调并参与肌少症发病的生理过程和分子水平信号通路。其发病机制是复杂的、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，用于鉴定、表征和定量老年人类肌肉和转基因小鼠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的线粒体蛋白表达模式进行比较，我们提出发现新的蛋白质和蛋白质形式（翻译后修饰），这些蛋白质和蛋白质形式可能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.