Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics

Endocrinol Metab (Seoul). 2021 Jun;36(3):478-490. doi: 10.3803/EnM.2021.1081. Epub 2021 Jun 28.

Abstract

Sarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.

Keywords: Aging; Clinical trial; Drug therapy; Molecular mechanisms of pharmacological action; Muscle, skeletal; Receptors, cell surface; Receptors, cytoplasmic and nuclear; Sarcopenia; Signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Homeostasis
  • Humans
  • Muscle, Skeletal / metabolism
  • Sarcopenia* / drug therapy
  • Sarcopenia* / metabolism
  • Signal Transduction