title: Human muscle satellite cells show age-related differential expression of S100B protein and RAGE.
abstract: During aging, skeletal muscles show reduced mass and functional capacity largely due to loss of the regenerative ability of satellite cells (SCs), the quiescent stem cells located beneath the basal lamina surrounding each myofiber. While both the external environment and intrinsic properties of SCs appear to contribute to the age-related SC deficiency, the latter ones have been poorly investigated especially in humans. In the present work, we analyzed several parameters of SCs derived from biopsies of vastus lateralis muscle from healthy non-trained young (28.7 ± 5.9 years; n = 10) and aged (77.3 ± 6.4 years; n = 11) people. Compared with young SCs, aged SCs showed impaired differentiation when cultured in differentiation medium, and exhibited the following: (1) reduced proliferation; (2) higher expression levels of S100B, a negative regulator of myoblast differentiation; (3) undetectable levels in growth medium of full-length RAGE (receptor for advanced glycation end products), a multiligand receptor of the immunoglobulin superfamily, the engagement of which enhances myoblast differentiation; and (4) lower expression levels of the transcription factors, MyoD and Pax7. Also, either overexpression of full-length RAGE or knockdown of S100B in aged SCs resulted in enhanced differentiation, while overexpression of either a non-transducing mutant of RAGE (RAGEΔcyto) or S100B in young SCs resulted in reduced differentiation compared with controls. Moreover, while aged SCs maintained the ability to respond to mitogenic factors (e.g., bFGF and S100B), they were no longer able to secrete these factors, unlike young SCs. These data support a role for intrinsic factors, besides the extracellular environment in the defective SC function in aged skeletal muscles.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, IIM, University of Perugia, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Beccafico
authors.forename: Francesca
authors.initials: F
authors.lastname: Riuzzi
authors.forename: Cristina
authors.initials: C
authors.lastname: Puglielli
authors.forename: Rosa
authors.initials: R
authors.lastname: Mancinelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Fulle
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Sorci
authors.forename: Rosario
authors.initials: R
authors.lastname: Donato
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D017570:MyoD Protein / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D051058:Oncogene Protein v-akt; D051763:PAX7 Transcription Factor / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000502:physiology; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017570:MyoD Protein; D009414:Nerve Growth Factors; D051763:PAX7 Transcription Factor; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D051058:Oncogene Protein v-akt; D048051:p38 Mitogen-Activated Protein Kinases