BACKGROUND INFORMATION: Aging of human skeletal muscle results in a decline in muscle mass and force, and excessive turnover of muscle fibres, such as in muscular dystrophies, further increases this decline. Although it has been shown in rodents, by cross-age transplantation of whole muscles, that the environment plays an important role in this process, the implication of proliferating aging of the muscle progenitors has been poorly investigated, particularly in humans, since the regulation of cell proliferation differs between rodents and humans. The myogenic differentiation of human myoblasts is regulated by the muscle-specific regulatory factors. Cross-talk between the muscle-specific regulatory factors and the cell cycle regulators is essential for differentiation. The aim of the present study was to determine the effects of replicative senescence on the myogenic programme of human myoblasts. RESULTS: We showed that senescent myoblasts, which could not re-enter the cell cycle, are still able to differentiate and form multinucleated myotubes. However, these myotubes are significantly smaller. The expression of muscle-specific regulatory factors and cell cycle regulators was analysed in proliferating myoblasts and compared with senescent cells. We have observed a delay and a decrease in the muscle-specific regulatory factors and the cyclin-dependent kinase inhibitor p57 during the early step of differentiation in senescent myoblasts, as well as an increase in the fibroblastic markers. CONCLUSIONS: Our results demonstrate that replicative senescence alters the expression of the factors triggering muscle differentiation in human myoblasts and could play a role in the regenerative defects observed in muscular diseases and during normal skeletal-muscle aging.
BACKGROUND INFORMATION: Aging of human skeletal muscle results in a decline in muscle mass and force, and excessive turnover of muscle fibres, such as in muscular dystrophies, further increases this decline. Although it has been shown in rodents, by cross-age transplantation of whole muscles, that the environment plays an important role in this process, the implication of proliferating aging of the muscle progenitors has been poorly investigated, particularly in humans, since the regulation of cell proliferation differs between rodents and humans. The myogenic differentiation of human myoblasts is regulated by the muscle-specific regulatory factors. Cross-talk between the muscle-specific regulatory factors and the cell cycle regulators is essential for differentiation. The aim of the present study was to determine the effects of replicative senescence on the myogenic programme of human myoblasts. RESULTS: We showed that senescent myoblasts, which could not re-enter the cell cycle, are still able to differentiate and form multinucleated myotubes. However, these myotubes are significantly smaller. The expression of muscle-specific regulatory factors and cell cycle regulators was analysed in proliferating myoblasts and compared with senescent cells. We have observed a delay and a decrease in the muscle-specific regulatory factors and the cyclin-dependent kinase inhibitor p57 during the early step of differentiation in senescent myoblasts, as well as an increase in the fibroblastic markers. CONCLUSIONS: Our results demonstrate that replicative senescence alters the expression of the factors triggering muscle differentiation in human myoblasts and could play a role in the regenerative defects observed in muscular diseases and during normal skeletal-muscle aging.
Authors: Ingo Riederer; Elisa Negroni; Maximilien Bencze; Annie Wolff; Ahmed Aamiri; James P Di Santo; Suse D Silva-Barbosa; Gillian Butler-Browne; Wilson Savino; Vincent Mouly Journal: Mol Ther Date: 2011-09-20 Impact factor: 11.454
Authors: Micah J Drummond; John J McCarthy; Mala Sinha; Heidi M Spratt; Elena Volpi; Karyn A Esser; Blake B Rasmussen Journal: Physiol Genomics Date: 2010-09-28 Impact factor: 3.107
Authors: Mats Hidestrand; Sonia Richards-Malcolm; Catherine M Gurley; Greg Nolen; Barry Grimes; Amanda Waterstrat; Gary Van Zant; Charlotte A Peterson Journal: J Gerontol A Biol Sci Med Sci Date: 2008-06 Impact factor: 6.053
Authors: Yvonne D Krom; Julie Dumonceaux; Kamel Mamchaoui; Bianca den Hamer; Virginie Mariot; Elisa Negroni; Linda N Geng; Nicolas Martin; Rabi Tawil; Stephen J Tapscott; Baziel G M van Engelen; Vincent Mouly; Gillian S Butler-Browne; Silvère M van der Maarel Journal: Am J Pathol Date: 2012-08-04 Impact factor: 4.307
Authors: Anna E Thalacker-Mercer; Louis J Dell'Italia; Xiangqin Cui; James M Cross; Marcas M Bamman Journal: Physiol Genomics Date: 2009-11-10 Impact factor: 3.107