This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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