Linking endocannabinoid system, palmitoylethanolamide, and sarcopenia in view of therapeutic implications

Sarcopenia, a debilitating skeletal muscle disease closely connected with elderly, is becoming a major public health problem with the increasing of life expectancy. With the aim to find effective, targeted, and side-effect-free therapies, understanding the endocannabinoid system (ECS) role in muscle homeostasis is of strategic importance. The skeletal muscle expresses all the ECS elements; in particular, a central role is played by the nuclear receptor PPARα and its main endogenous ligand, palmitoylethanolamide (PEA), an endocannabinoid-like molecule with an important antiinflammatory effect. It is worth highlighting that in the muscle, the expression level of both PPARα receptor and its coactivator PGC1a decreases with age, suggesting a causative relation between the lower PPARα function and sarcopenia. Therefore, the administration of PEA to the muscle can be a promising approach to counteract sarcopenia. In this regard, to promote the muscle targeting, innovative drug delivery systems, such as solid lipid nanoparticles, can be considered.