Therapies for sarcopenia and regeneration of old skeletal muscles: more a case of old tissue architecture than old stem cells.

Age related loss of skeletal muscle mass and function (sarcopenia) reduces independence and the quality of life for individuals, and leads to falls and fractures with escalating health costs for the rapidly aging human population. Thus there is much interest in developing interventions to reduce sarcopenia. One area that has attracted recent attention is the proposed use of myogenic stem cells to improve regeneration of old muscles. This mini-review challenges the fundamental need for myogenic stem cell therapy for sarcopenia. It presents evidence that demonstrates the excellent capacity of myogenic stem cells from very old rodent and human muscles to form new muscles after experimental myofiber necrosis. The many factors required for successful muscle regeneration are considered with a strong focus on integration of components of old muscle bioarchitecture. The fundamental role of satellite cells in homeostasis of normal aging muscles and the incidence of endogenous regeneration in old muscles is questioned. These issues, combined with problems for clinical myogenic stem cell therapies for severe muscle diseases, raise fundamental concerns about the justification for myogenic stem cell therapy for sarcopenia.