LABS’ SESSION: DISSECTING ANDROGEN RECEPTOR ON SKELETAL MUSCLE CELLS: D.A.RE PROJECT

Introduction: Androgens act in various non-reproductive cells, including muscle and bone cells, through the androgen receptor (AR), increasing muscle size and strength in young as well as old men. The androgen deficiency is often associated not only with ageing but also with chronic-diseases. Purpose: The project aims to increase knowledge of androgen action in the skeletal muscle and its variations in young adults, middle-aged and old men. Method: We performed a translational, crosssectional research including 60 healthy subjects > 30 y.o. (20 subjects aged 30-45; 20 subjects aged 45-65; 20 subjects aged > 65). We excluded all subjects with any disease that might affect the neuromuscular system. Three subjects from each group underwent a muscle biopsy. Results: We analyzed the phosphorylation status of the signalling effectors linking the AR non-genomic axis with cytoskeleton organization in human skeletal muscles biopsies. Lysates from old women skeletal muscle biopsies exhibited a stronger phosphorylation in both Ser-2152 filamin A and Tyr-118 paxillin, as compared with biopsies from young women. Conversely, the expression of AR and ER-α and the phosphorylation status of ERK1/2 were weaker in samples from old women, as compared with that detected in biopsies from young women. Conclusions: The number of biopsies done so far is too small to drive any definitive conclusion. Expected results might help us in targeting the non-genomic functions of skeletal muscle AR using new SARMs or stapled-peptides displacing AR/filamin A or inhibiting AR/Src interaction to improve the clinical outcome of sarcopenia and agerelated diseases.