Different intrinsic properties of young and aged human satellite cells.

During aging, skeletal muscles undergo a decline in 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) vs age-related intrinsic cellular properties of the SCs (1). In the present work we analyzed several parameters of SCs derived from biopsies from Vastus Lateralis muscle from both 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 ability [i.e., lower extent of fusion into myotubes and reduced expression of myogenin and myosin heavy chain, when cultured in differentiation medium (DM)], compared with young SCs, and were characterized by the following: i) a stronger expression of S100B, a Ca2+-binding protein the overexpression of which has been found to interfere with myoblast differentiation (Tubaro C et al., submitted for publication); ii) undetectable levels of full-length RAGE (receptor for advanced glycation end products) protein, a multiligand receptor the engagement of which enhances myoblast differentiation (2), in growth medium (GM), and cytosolic instead of membrane localization of RAGE in DM; and iii) lower expression levels of MyoD and Pax7 transcription factors, in both GM and DM. These data point to an important role for intrinsic factors, besides extrinsic factors, in defective SC function during aging.