Atrogin-1, MuRF-1, and sarcopenia.

Sarcopenia is one of the leading causes of disability in the elderly. Despite the growing prevalence of sarcopenia, the molecular mechanisms that control aging-related changes in muscle mass are not fully understood. The ubiquitin proteasome system is one of the major pathways that regulate muscle protein degradation, and this system plays a central role in controlling muscle size. Atrogin-1 and MuRF-1 are two E3 ubiquitin ligases that are important regulators of ubiquitin-mediated protein degradation in skeletal muscle. In this review, we will discuss: (i) aging-related changes to skeletal muscle structure and function; (ii) the regulation of protein synthesis and protein degradation by IGF-1, TGF-β, and myostatin, with emphasis on the control of atrogin-1 and MuRF-1 expression; and (iii) the potential for modulating atrogin-1 and MuRF-1 expression to treat or prevent sarcopenia.