Proteomics of skeletal muscle aging
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. Proteomics
(Impact Factor: 3.81).
02/2009; 9(4):989-1003. DOI: 10.1002/pmic.200800365
Extended human longevity has resulted in increasing numbers of elderly persons in the general population. However, old age is also associated with a variety of serious physical disorders. Frailty among sedentary elderly patients is related to the impaired structure and function of contractile fibers. Biochemical research into cellular mechanisms that underlie sarcopenia promises to acquire the scientific basis of evidence to aid the development of new diagnostic and therapeutic strategies. The recent application of MS-based proteomic methodology has identified a large cohort of disease-specific markers of sarcopenia. This review critically examines the biomedical implications of the results obtained from the proteomic screening of both aged human muscle and established animal models of sarcopenia. Substantial alterations in proteins involved in key metabolic pathways, regulatory and contractile elements of the actomyosin apparatus, myofibrillar remodeling and the cellular stress response are discussed. A multi-factorial etiology appears to be the basis for a slower-twitching aged fiber population, which exhibits a shift to more aerobic-oxidative metabolism. It is hoped that the detailed biomedical characterization of the newly identified biomarkers of sarcopenia will translate into better treatment options for reversing age-dependent muscle degeneration, which could improve the standard of living for a large portion of society.
Available from: Choi Jeong-yi
- "Although differential expression profiles of mRNA provide important information, and such genomic expression profiles of muscle aging have been described   , expression profile analyses of proteins are needed to better understand the molecular mechanisms that are essential to the muscle aging process. Proteomic technology, including DIGE and 2DE, has been used to catalog proteins that are expressed in skeletal muscle during aging    . Though not combined with quantitative analysis, SDS-PAGE-based shotgun proteomics has provided more comprehensive characterization of human skeletal muscle proteome . "
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ABSTRACT: Aging is associated with a progressive loss of skeletal muscular function that often leads to progressive disability and loss of independence. Although muscle aging is well documented, the molecular mechanisms of this condition still remain unclear. To gain greater insight into the changes associated with aging of skeletal muscle, we performed quantitative proteomic analyses on young (6-month) and aged (27-month) mouse gastrocnemius muscles using mTRAQ stable isotope mass tags. We identified and quantified a total of 4,585 peptides corresponding to 236 proteins (protein probability > 0.9). Among them, 33 proteins were more than 1.5-fold up-regulated and 20 proteins were more than 1.5-fold down-regulated in aged muscle compared with young muscle. An ontological analysis revealed that differentially expressed proteins belonged to distinct functional groups, including ion homeostasis, energy metabolism, protein turnover, and Ca(2+) signaling. Identified proteins included aralar1, β-enolase, fatty acid-binding protein 3 (Fabp3), 3-hydroxyacyl-CoA dehydrogenase (Hadh), F-box protein 22 (Fbxo22), F-box and leucine-rich repeat protein 18 (Fbxl18), voltage-dependent L-type calcium channel subunit beta-1 (Cacnb1), ryanodine receptor (RyR), and calsequestrin. Ectopic expression of calsequestrin in C2C12 myoblast resulted in decreased activity of nuclear factor of activated T-cells (NFAT) and increased levels of atrogin-1 and MuRF1 E3 ligase, suggesting that these differentially expressed proteins are involved in muscle aging.
Available from: Fabian Sanchis-Gomar
- "This is particularly true considering that the simple physical assessment is often misleading, because older persons might be able to compensate or even overcompensate for incident impairments, especially in the early stage of physiological decrement. A thoughtful description of the major pathways involved in sarcopenia and age-related changes in skeletal muscles (i.e., progressive denervation, excitation-contraction uncoupling, anatomical alterations, increased cellular stress, hormonal and metabolic disturbances ) is outside the aim of this article , since it is comprehensively discussed in other chapters of this special issue about the multidomain mobility lab in older persons. Moreover, it is not our intention to thoughtfully discuss, classify, or present results of all the available studies about the putative biochemical correlates of functional decline in the elderly, but rather to provide a critical overview about the range of potential useful biomarkers that have been identified in selected and more representative clinical studies. "
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ABSTRACT: Due to the progressive ageing of the worldwide population, prevention and treatment of late-life dysfunctions, including functional decline and mobility limitations, represent leading targets of scientists and clinicians, but are also receiving growing attention from governments and healthcare systems. The early identification of elderly patients more prone to physical decline represents a crucial step for establishing preventive measures. Although functional capacity can easily be assessed, the use of additional criteria that anticipate the onset of mobility limitations seems much more advantageous. The most challenging issues in the identification of biological markers for assessing the risk of functional decline in the elderly originates from the complex and multifaceted pathogenesis of sarcopenia and the resulting physiological decrement, so that bridging the gap between basic research and clinical practice may appear intricate. Nevertheless, several lines of evidence now confirm the existence of negative associations between functional mobility and values of hemoglobin, total and HDL-cholesterol, vitamin D, testosterone, adiponectin and antioxidants such carotenoids, vitamin C and E, selenium and magnesium, whereas positive associations have been reported with the values of uric acid, white blood cells, plasma and blood viscosity, erythrocyte sedimentation rate (ESR), triglycerides, homocysteine, plasma glucose, glycated hemoglobin (HbA1c), markers of renal functions (i.e., creatine and cystatin C), insulin-like growth factor-1 (IGF-1), as well as several inflammatory (e.g., C reactive protein, Intereleukin-6, Interleukin-1 receptor antagonist), hemostatic (e.g., fibrinogen, Von Willebrand Factor, factors VIII and IX) and oxidative (oxidized lipoproteins, 8-oxo-7,8-2'-deoxyguanosine, protein carbonylation) biomarkers. In the foreseeable future, proteomic studies might predictably help identify novel associations between putative biomarkers and functional decline.
Available from: Cintia Matsumura
- "Among these 21 proteins, only annexin A1 showed a distinct pattern of change (increased or decreased) depending on the comparison (39% decreased in control DIA vs. control EOM and 51% increased in mdx DIA vs. mdx EOM). The remaining 20 proteins, most  were decreased in DIA vs. EOM (collagen alpha-1 and alpha-2; myosin 3, 4 and 11; SERCA 1; calsequestrin 1; sarcalumenin; aspartate aminotransferase; tropomyosin alpha -3 and mitochondrial 2-oxoglutarate/malate carrier protein), with a few  proteins increased in DIA×EOM (voltage-dependent anion selective channel protein 1; myosin 1, regulatory light chain 2 and light chain 3; uncharacterized protein C1orf93 homolog; isocitrate dehydrogenase (NADP) mitochondrial; L-lactate dehydrogenase B chain; C-X-C chemokine receptor type 1, and SERCA 2). "
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ABSTRACT: Duchenne muscular dystrophy (DMD) is the most common childhood myopathy, characterized by muscle loss and cardiorespiratory failure. While the genetic basis of DMD is well established, secondary mechanisms associated with dystrophic pathophysiology are not fully clarified yet. In order to obtain new insights into the molecular mechanisms of muscle dystrophy during earlier stages of the disease, we performed a comparative proteomic profile of the spared extraocular muscles (EOM) vs. affected diaphragm from the mdx mice, using a label based shotgun proteomic approach. Out of the 857 identified proteins, 42 to 62 proteins had differential abundance of peptide ions. The calcium-handling proteins sarcalumenin and calsequestrin-1 were increased in control EOM compared with control DIA, reinforcing the view that constitutional properties of EOM are important for their protection against myonecrosis. The finding that galectin-1 (muscle regeneration), annexin A1 (anti-inflammatory) and HSP 47 (fibrosis) were increased in dystrophic diaphragm provides novel insights into the mechanisms through which mdx affected muscles are able to counteract dystrophy, during the early stage of the disease. Overall, the shotgun technique proved to be suitable to perform quantitative comparisons between distinct dystrophic muscles and allowed the suggestion of new potential biomarkers and drug targets for dystrophinopaties.
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