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human_muscle_stem_cell
Human muscle satellite cells show age-related differential
expression of S100B protein and RAGE
Sara Beccafico Francesca Riuzzi
Cristina Puglielli Rosa Mancinelli
Stefania Fulle Guglielmo Sorci Rosario Donato
Received: 30 July 2010 /Accepted: 15 November 2010
# American Aging Association 2010
Abstract During aging, skeletal muscles show re-
duced 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 differenti-
ation; (3) undetectable levels in growth medium of full-
length RAGE (receptor for advanced glycation end
products), a multiligand receptor of the immunoglobu-
lin 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, be
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