During aging, skeletal muscles show reduced functional capacity due to loss of the regenerative ability of satellite cells (SCs), the quiescent stem cells located beneath the basal lamina surrounding each myofiber. Both age-related extrinsic factors and age-related intrinsic properties of SCs appear to contribute to SC efficiency (Aging Cell 7 (2008) 590-8). In the present work we analyzed several parameters of SCs derived from biopsies of Vastus Lateralis muscle from healthy non-trained young and aged humans (male and female, divided into young [mean age 31.0 ± 5.35 years; n=7] and aged [mean age 76.44 ± 6.12 years; n=9]). Compared to young SCs, aged SCs showed impaired differentiation, i.e. reduced myotube formation and reduced expression of myogenin and myosin heavy chain when cultured in differentiation medium (DM), and exhibited the following: i) reduced proliferation; ii) higher expression levels of S100B, a Ca2+-binding protein and negative regulator of myoblast differentiation (submitted for publication); iii) undetectable levels of full-length RAGE (receptor for advanced glycation end products), a multiligand receptor of the immunoglobulin superfamily the engagement of which enhances myoblast differentiation (Mol Cell Biol 24 (2004) 4880-4894; J Biol Chem 281 (2006) 8242-8253), and presence of a truncated form of RAGE in growth medium (GM) the amount of which decreased in DM in parallel with appearance of full-length RAGE; and iv) lower expression levels of the transcription factors, MyoD and Pax7, in both GM and DM. Also, transient transfection of young SCs with S100B expression vector resulted in reduced differentiation compared to controls (i.e., acquisition of an aged phenotype), while either transfection of aged SCs with full-length RAGE expression vector or knocking down S100B by siRNA resulted in enhanced differentiation (i.e., acquisition of a young phenotype). These data point to an important role for intrinsic factors (e.g., MyoD, Pax7, S100B and RAGE) in defective SC function in aged skeletal muscles.
Young and Aged Human Muscle Satellite Cells Show Differential Expression of S100B Protein and RAGE.
BECCAFICO, SARA;RIUZZI, Francesca;SORCI, Guglielmo;DONATO, Rosario Francesco
2009
Abstract
During aging, skeletal muscles show reduced functional capacity due to loss of the regenerative ability of satellite cells (SCs), the quiescent stem cells located beneath the basal lamina surrounding each myofiber. Both age-related extrinsic factors and age-related intrinsic properties of SCs appear to contribute to SC efficiency (Aging Cell 7 (2008) 590-8). In the present work we analyzed several parameters of SCs derived from biopsies of Vastus Lateralis muscle from healthy non-trained young and aged humans (male and female, divided into young [mean age 31.0 ± 5.35 years; n=7] and aged [mean age 76.44 ± 6.12 years; n=9]). Compared to young SCs, aged SCs showed impaired differentiation, i.e. reduced myotube formation and reduced expression of myogenin and myosin heavy chain when cultured in differentiation medium (DM), and exhibited the following: i) reduced proliferation; ii) higher expression levels of S100B, a Ca2+-binding protein and negative regulator of myoblast differentiation (submitted for publication); iii) undetectable levels of full-length RAGE (receptor for advanced glycation end products), a multiligand receptor of the immunoglobulin superfamily the engagement of which enhances myoblast differentiation (Mol Cell Biol 24 (2004) 4880-4894; J Biol Chem 281 (2006) 8242-8253), and presence of a truncated form of RAGE in growth medium (GM) the amount of which decreased in DM in parallel with appearance of full-length RAGE; and iv) lower expression levels of the transcription factors, MyoD and Pax7, in both GM and DM. Also, transient transfection of young SCs with S100B expression vector resulted in reduced differentiation compared to controls (i.e., acquisition of an aged phenotype), while either transfection of aged SCs with full-length RAGE expression vector or knocking down S100B by siRNA resulted in enhanced differentiation (i.e., acquisition of a young phenotype). These data point to an important role for intrinsic factors (e.g., MyoD, Pax7, S100B and RAGE) in defective SC function in aged skeletal muscles.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
