Sarcopenia: pharmacology of today and tomorrow

Abstract

Sarcopenia remains largely undiagnosed and undertreated because of the lack of a universally accepted definition, effective ways to measure it, and identification of the outcomes that should guide treatment efficacy. An ever-growing number of clinicians and researchers along with funding and regulatory agencies have gradually recognized that sarcopenia is a human condition that requires both prevention and treatment. In this article, we review sarcopenia and its common and less known pharmacological treatments, attempt to define sarcopenia in its broader context, and present some new ideas for potential future treatment for this devastating condition.

Fig. 1.

Schematic drawing of a proposed model illustrating the known influences on the development of sarcopenia and the consequences of treating and not treating this human disease.

Fig. 2.

Chemical structures of key drugs, compounds, and supplements discussed in this Perspective are shown in detail (A, testosterone; B, DHEA; C, vitamin D₃; D, ursolic acid; E, enalapril; F, bortezomib; G, ALA; H, DHA; I, EPA; J, Debio-025; K, AICAR).

Fig. 3.

Schematic drawing illustrating some of the essential molecular pathways that can lead to anabolism or catabolism in skeletal muscles. Effective modulation of these pathways by existing and in-development agents could favor the balance toward anabolism and hypertrophy. It is important to observe that mechanisms that are not currently addressed by any of the compounds but seem to be affected by resistance exercise training are those that enhance muscle strength without necessarily increasing muscle mass. TNFα, tumor necrosis factor-α; TNFα R, tumor necrosis factor-α receptor; NFκB, nuclear factor κB; mTOR, mammalian target of rapamycin; GSK-3β, glycogen synthase kinase-3; RTK, receptor tyrosine kinases; PI3K, phosphatidylinositol 3-kinase; RAG, RAG, RAS-related GTP-binding protein; IGF, insulin-like growth factor; IL, interleukin.