Titre :
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Effect of cellular senescence and aging on human muscle precursors : Acte de colloque : 4ème colloque international de Myologie (9-13 mai 2011; Lille (France))
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contenu dans :
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Auteurs :
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Le Bihan MC ;
Le Bihan MC ;
Bigot A ;
Rogowska-Wrzesinska A ;
Jensen SS ;
Laine J ;
Baraibar M ;
Friguet B ;
Dennis JL ;
Jensen ON ;
Coulton GR ;
Mouly V
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Type de document :
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Article
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Editeur :
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AFM-TELETHON, 2011
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Pages :
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p 7
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Langues:
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Anglais
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Mots-clés :
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colloque
;
dégénérescence maculaire
;
facteur de croissance
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glycosylation
;
masse musculaire
;
myoblaste
;
perte pondérale
;
spectroscopie
;
technique de chimie analytique
;
vieillissement
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Résumé :
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With age, there is a gradual decline in the effectiveness of the regenerative response of skeletal muscle to damage which is accompanied by tissue remodeling such as muscle fiber atrophy, fibrosis and a general loss of muscle mass and function. The decline in regenerative capacity may be related to the decrease in the number of muscle precursor cells (satellite cells) as well as to an age-related decline in satellite cell function. In previous studies we have demonstrated a delay and a decrease in muscle-specific regulatory factors and the cyclin-dependent kinase inhibitor p57 resulting in a defective differentiation in senescent myoblasts. We have also found that human myoblasts during senescence accumulate oxidized proteins and proteins modified by lipid peroxidation and glycoxidation adducts. Many of these oxidized proteins are enzymes involved in cellular metabolism, such as glycolysis and gluconeogenesis. These cells also show a decreased proteosome activity which in combination with increased oxidative stress may explain the accumulation of damaged proteins. It has been also suggested that the decreased level of circulating trophic factors that occurs with age could contribute to the decrease in muscle mass, force and regenerative capacity described in the elderly. We know that 1) communication between cells involves the secretion of proteins which bind to receptors on neighbouring cells to elicit intracellular changes and 2) secreted proteins ("secretome") regulate activation, proliferation and differentiation of muscle progenitors. A time course of myoblast secretion at early passage and late passages revealed a 3 to 4-fold decrease in the total amount of protein secreted during senescence. We have used 3 different expression profiling strategies: 1) 2D gel electrophoresis/mass spectrometry (2DE/MS); 2) Luminex based assay; 3) mass spectrometry (MS) based approaches (iTRaq) to analyse the secretome of aging myoblasts. We identified 98 molecules differentially "secreted" during muscle ageing in vitro. The senescent myoblasts express a similar panel of inflammatory cytokines as those reported by Campisi et al for senescent fibroblasts. These changes are associated with an upregulation and glycosylation of key regulators involved in matrix remodelling. All of the modifications we have described could play a role in tissue remodeling and regenerative defects observed during normal skeletal-muscle aging as well as in some muscle diseases, particularly those involving cycles of degeneration.
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