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

Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics

• Yoon JH
• Kwon KS

• KMID: 2517637
• DOI: http://doi.org/10.3803/EnM.2021.1081

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.

Keyword

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

Figure

• 

  Fig. 1. Cell signaling pathways and pharmacological strategies for sarcopenia. GHSR, growth hormone secretagogues receptor or ghrelin receptor; IGF-1R, insulin-like growth factor 1 receptor; ACE, angiotensin-converting enzyme; ActRIIB, activin type II receptor; Ang1, angiotensin I; Ang2, angiotensin II; AGTR1, angiotensin II receptor type 1; SARM, selective androgen receptor modulator; AR, androgen receptor; VDR, vitamin D receptor; mTOR, mammalian target of the rapamycin; FOXO, forkhead box O.

• 

  Fig. 2. Distribution of target families of small-molecule drugs in sarcopenia. Related data are described on ClinicalTrials.gov, and the figure includes data up to March 2021. IS, indoxyl sulfate; XO, xanthine oxidase.

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  Fig. 3. The current status of articles on sarcopenia and cell signaling receptors. A literature search was conducted in PubMed (keyword: sarcopenia, receptor, and/or related-term) and the relevant data extend up to March 2021. IGF-1, insulin-like growth factor 1; IL-15, interleukin 15.

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