Proteomic Profiling of Fast-To-Slow Muscle Transitions during Aging

Abstract

Old age is associated with a large spectrum of physical ailments, including muscle wasting. Skeletal muscle degeneration drastically increases the risk of poor balance, frequent falling and impaired mobility in the elderly. In order to identify new therapeutic targets to halt or even reverse age-dependent muscle weakness and improve diagnostic methods to properly evaluate sarcopenia as a common geriatric syndrome, there is an urgent need to establish a reliable biomarker signature of muscle aging. In this respect, mass spectrometry-based proteomics has been successfully applied for studying crude extracts and subcellular fractions from aged animal and human muscle tissues to identify novel aging marker proteins. This review focuses on key physiological and metabolic aspects of sarcopenia, i.e., age-related muscle fiber transitions and metabolic shifts in aging muscle as revealed by proteomics. Over the last decade, proteomic profiling studies have clearly confirmed the idea that sarcopenia is based on a multi-factorial pathophysiology and that a glycolytic-to-oxidative shift occurs in slower-twitching senescent muscles. Both, newly identified protein factors and confirmed alterations in crucial metabolic and contractile elements can now be employed to establish a sarcopenia-specific biomarker signature.

Keywords: biomarker; mass spectrometry; muscle aging; muscle transitions; proteomics; sarcopenia.

Figure 1

Fast-to-slow muscle transitions during muscle aging as revealed by proteomics. Shown is a diagram of the effect of aging on the main contractile and regulatory proteins of the actomyosin apparatus. Proteomic profiling has clearly established an age-related shift to slower protein isoforms of myosin heavy chain (MHC), myosin light chain (MLC), actin (Act), and tropomyosin (TM), as well as troponin subunits (TnC, TnT, TnI). Besides the slowing of contractile force, the progressive loss of muscle mass and resulting contractile weakness are the main cause of sarcopenia of old age. The background shows a transverse section of gastrocnemius muscle stained with hematoxylin and eosin.

Figure 2

Glycolytic-to-oxidative shift during muscle aging as revealed by proteomics. Shown is a diagram of the main bioenergetic pathways for the provision of adenosine triphosphate (ATP) for the contractile activity of skeletal muscle fibers including glycolysis, the creatine phosphate shuttle, the citric acid cycle and oxidative phosphorylation. Proteomic profiling has clearly established an increase in mitochondrial enzymes and concomitant decrease in glycolytic enzymes during the fast-to-slow transformation process in aging skeletal muscle tissue. The background shows a transverse section of gastrocnemius muscle that was histochemically stained for the presence of the mitochondrial marker enzyme succinate dehydrogenase.