Proteomic and Biochemical Profiling of Aged Skeletal Muscle

Abstract

Muscle proteomics is concerned with the large-scale profiling of the protein complement from contractile tissues in order to enhance our biochemical knowledge of fundamental physiological processes, as well as the pathophysiological mechanisms that underlie neuromuscular disorders. Since the loss of skeletal muscle mass and strength is one of the most striking features of the senescent body, a large number of proteomic studies have recently attempted the global analysis of age-related fibre degeneration. Although the large size of the muscle proteome and its broad range of expression levels complicates a comprehensive cataloguing of the entire muscle protein complement, mass spectrometry-based proteomic studies have succeeded in the identification of many novel sarcopenia-specific markers. Changes in the expression of affected muscle proteins, as well as altered post-translational modifications, can now be used to establish a reliable biomarker signature of age-dependent fibre wasting. Muscle proteins that are changed during aging belong to the regulatory and contractile elements of the actomyosin apparatus, key bioenergetic pathways, the myofibrillar remodeling machinery and the cellular stress response. The proteomic profiling of crude muscle extracts and distinct subcellular fractions agrees with the notion that sarcopenia of old age is due to a multi-factorial pathology. Changes in muscle markers of the contractile apparatus and energy metabolism strongly indicate a fast-to-slow fibre transition process and a shift to more aerobic-oxidative metabolism during aging. In the long-term, newly established biomarkers of sarcopenia might be useful for the design of improved diagnostic procedures and the identification of new therapeutic targets.