STUDIO DELL'EFFETTO PREVENTIVO DELLA METFORMINA SUI DANNI ASSOCIATI ALLA SEDENTARIETA' IN MODELLI MURINI

Metformin (METF), historical antihyperglycemic drug, is a likely candidate for lifespan extension, treatment and prevention of sedentariness damages, insulin resistance and obesity. Skeletal muscle is a highly adaptable tissue, capable to increase its mass in response to exercise and to regenerate new fibrils after damage. Aims of this work were to investigate METF ability to prevent sedentariness injury and enhance skeletal muscle function. Sedentary 12-weeks old C57BL/6 mice were treated with METF (250 mg/kg per day, in drinking water) for 60 days. METF role on skeletal muscle differentiation was studied in vitro using murine C2C12 myoblasts. Muscular performance evaluation revealed that METF enhanced mice physical performance. Tissues analysis indicated that in liver METF increased AMPK and CAMKII signaling, while inactivated ERKs, principal kinases involved in hepatic stress conditions. In skeletal muscle, METF activated AKT, key kinase in skeletal muscle maintenance. In in vitro studies, Immunofluorescence and Western blot analysis showed that METF did not modify the C2C12 proliferation capacity, while positively influenced the differentiation process and myotube maturation. Together, our novel results suggest that METF may have a positive action not only on the promotion of healthy aging but also on the prevention of sedentariness damages.