Coming back: autophagy in cachexia

Purpose of the review Cachexia is a complex syndrome characterized by body weight loss, tissue wasting, systemic inflammation, metabolic abnormalities and altered nutritional status. One of the most prominent features of cachexia is the loss of muscle mass, mainly due to increased protein degradation rates. The review is aimed at discussing the involvement of autophagy in the pathogenesis of muscle wasting in cachexia. Recent findings Modulations of muscle mass in the adult reflect an inbalance between protein synthesis and degradation rates. Muscle depletion in cachexia is associated with increased protein breakdown, mainly involving the pathways dependent on ubiquitin-proteasome and autophagy-lysosomes. This latter, in particular, was considered not relevant for a long time. Just in the last years autophagy was shown to contribute to the pathogenesis of muscle wasting not only in myopathies due to intrinsic muscle defects, but also in muscle depletion associated with conditions such as sepsis, chronic obstructive pulmonary disease, glucocorticoid treatment, cancer cachexia, aging. Summary The present review highlights that both excess or defective autophagy are relevant to the onset of muscle depletion, and draws some considerations about possible therapeutic intervention aimed at modulating autophagy in order to improve muscle trophism (see Video, Supplementary Digital Content 1).