In today's (September 30th) online edition of EMBO Molecular Medicine, M. E. Carlson et al. from the Univ. of California, Berkeley reported the results of their study on the delineating the molecular pathway(s) that lead aging in human skeletal muscle. Although satellite cells are found in aged muscle, the investigators noted that these muscle stem cells were not activated during muscle atrophy or damage. In a two-armed human study, muscle biopsies were obtained from quadriceps of young (av. 2.6 yrs.) and old (av. 71.3 yrs) subjects and the legs immobilized in a cast for 2 weeks. The study results showed that immobilzation mildly affected the young muscle tissue with respect to tissue maintenance and functionality. However, after the casts were removed from older patients, muscle biospsies showed that immobilization resulted in tissue inflammation and scarring. The inability to activate the quiescent satellite cells in old muscle was attributed to the diminished activation of Notch concomitant with elevated levels of the inflammatory cytokine, TGF-β/pSmad3. The study also revealed that MAPK signaling, which in turn activates Notch, declines with age in the satellite cells. However, activating MAPK/Notch signaling restores the "youthful" myogenic responses from old humans (70 yrs) to responses observed in 20 year old humans. This observation suggests that satellite cells remain intrinsically young and it's the aging microenvironment within the stem cell tissue compartments which results in a steady loss of muscle maintenance and functionality. The authors concluded from their findings that the aging process which affects muscle can be reversed to a youthful state if specific molecular pathways are targeted.