Molecular signaling homology across muscle wasting conditions

keletal muscle tissue is remarkably simple as to its cell types, in comparison to other tissues: it is constituted by a terminally differentiated, gigantic syncytial cell type (the myofiber) and a quiescent, mononucleated stem cell (the satellite cell, SC). The latter grants regeneration and homeostasis following damage or atrophy, with the possible intervention of additional myogenic stem cells from the endomysium. In case of damage, the muscle fiber «is too big to fail» and survival is guaranteed by involving new resources, in the form of additional nuclei coming from the SC. Furthermore, the myofiber has a striking adaptative capacity to cope with the variable demand in contractile activity and mechanical load, by modulating the bulk protein reserve and the number and function of sarcomeres. Based on the aforementioned characteristics of the system - a tissue with two components, having dicotomial responses such as fiber atrophy/hypertrophy or SC proliferation/differentiation - it is plausible to imagine that muscle adaptative responses are always the same, regardless of the stimulus. In other words, one would expect molecular signaling homology across muscle wasting conditions independently of the primary cause of wasting. In this perspective, for instance one could consider cachexia as an accelerated muscle wasting condition which differs from sarcopenia simply for its kinetics and severity. This way of reasoning has very relevant implications for funding agencies, researchers and physicians and, ultimately, the general population: for instance, common mechanisms would imply that findings related to muscle wasting associated to one disease would have fallouts for other disease-related muscle wasting conditions. It is therefore of pivotal importance to discuss to which extent and how muscle wasting conditions differ from each other and which are, if any, the major regulatory factors involved. We will present some examples of such a homology, with emphasis on the crosstalk between: p53/Growth Factors, NF-kappaB/Serum Response Factor, and Pax7/Muscle Regulatory Factors. References Coletti D, Daou N, Hassani M, Li Z, Parlakian A. Serum Response Factor in muscle tissues: from development to ageing. Eur J Transl Myol. 2016; 26(2):6008 Coletti D, Teodori L, Li Z, Bernaudin JF, Adamo S. Restoration versus reconstruction: cellular mechanisms of skin, nerve and muscle regeneration compared. Regen Med Res, 1:4, 2013 Drescher C, Konishi M, Ebner N, Springer J. Loss of muscle mass: current developments in cachexia and sarcopenia focused on biomarkers and treatment. J Cachexia Sarcopenia Muscle. 2015 Dec;6(4):303-11.