Differential expression of S100B protein and RAGE in young and aged human satellite cells.

During aging, skeletal muscles undergo a decline of functional capacity due to loss of regenerative ability of satellite cells (SCs), the quiescent stem cells located beneath the basal lamina surrounding each myofiber. There is debate about the influence of age-related extrinsic factors on SC efficiency (the SC niche theory) vs. age-related intrinsic properties of SCs (1). In the present work we analyzed several parameters of SCs derived from biopsies from Vastus Lateralis muscle from healthy non-trained young and aged humans (male and female, divided into young [mean age 31.6 ± 3.6 years; n=5] and aged [mean age 77.3 ± 5.8 years; n=7]). Aged SCs showed impaired differentiation manifested as a smaller extent of fusion into myotubes and reduced expression of myogenin and myosin heavy chain when cultured in differentiation medium (DM), compared to young SCs, and were characterized by the following: 1) reduced proliferation; 2) higher expression levels of S100B, a Ca2+-binding protein the overexpression of which has been found to interfere with myoblast differentiation (C. Tubaro et al., submitted for publication); 3) undetectable levels of full-length RAGE (receptor for advanced glycation end products) protein, a multiligand receptor of the immunoglobulin superfamily the engagement of which enhances myoblast differentiation (2), and presence of a membrane-bound, truncated form of RAGE in growth medium (GM) the amount of which decreased in DM in parallel with appearance of full-length RAGE; and 4) 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 a reduced differentiation potential compared to controls (i.e., acquisition of an aged phenotype), while transfection of aged SCs with full-length RAGE expression vector resulted in an enhanced differentiation (i.e., acquisition of a young phenotype). By contrast, transient transfection of young SCs with RAGEΔcyto, a RAGE mutant lacking the cytoplasmic and transducing domain, resulted in a reduced differentiation potential compared to controls. These data point to an important role for intrinsic factors (e.g., MyoD, Pax7, S100B and RAGE), besides extrinsic factors, in defective SC function in aged skeletal muscles. 1. Gopinath SD and Rando TA (2008) Aging Cell 7:590-8; 2. Sorci G et al. (2004) Mol Cell Biol 24:4880-94.