Hippo pathway effectors YAP and TAZ and their association with skeletal muscle ageing

Abstract

Skeletal muscle atrophy commonly occurs during ageing, thus pathways that regulate muscle mass may represent a potential therapeutic avenue for interventions. In this review, we explored the Hippo signalling pathway which plays an essential role in human oncogenesis and the pathway’s influence on myogenesis and satellite cell functions, on supporting cells such as fibroblasts, and autophagy. YAP/TAZ was found to regulate both myoblast proliferation and differentiation, albeit with unique roles. Additionally, YAP/TAZ has different functions depending on the expressing cell type, making simple inference of their effects difficult. Studies in cancers have shown that the Hippo pathway influenced the autophagy pathway, although with mixed results. Most of the present researches on YAP/TAZ are focused on its oncogenicity and further studies are needed to translate these findings to physiological ageing. Taken together, the modulation of YAP/TAZ or the Hippo pathway in general may offer potential new strategies for the prevention or treatment of ageing.

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Funding

We thank the Kementerian Riset, Teknologi, dan Pendidikan Tinggi that supported our research through the World Class Research grant with grant number 1827/UN6.3.1/LT/2020 to Iwan Setiawan and we also thanked the Kementerian Riset, Teknologi, dan Pendidikan Tinggi that supported our research through the World Class Research grant with grant number UN6.3.1/LT/2021 Ronny Lesmana and to Direktorat Jenderal Pendidikan Tinggi Indonesia for the Program Magister Doktoral Sarjana Unggul (PMDSU) grant to Ardo Sanjaya with grant number 211/SP2H/LT/DRPM/2020.

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Iwan Setiawan, Ardo Sanjaya, and Ronny Lesmana conceived the idea for the article. The literature search was conducted by Iwan Setiawan, Ardo Sanjaya, Ronny Lesmana, Hanna Goenawan, and Paul M Yen. All authors contributed to drafting and critical revision of the article.

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Correspondence to Ronny Lesmana.

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Key points

•Skeletal muscle mass is regulated through YAP/TAZ effect on myoblast proliferation and differentiation which is altered in aging.

•Ageing is associated with low physical activity which may alter YAP/TAZ levels in myoblasts.

•Ageing causes stiff extracellular matrix and induces further fibrosis through YAP/TAZ.

•YAP has been shown to promote stemness of satellite cells and may be beneficial in ageing.

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Setiawan, I., Sanjaya, A., Lesmana, R. et al. Hippo pathway effectors YAP and TAZ and their association with skeletal muscle ageing. J Physiol Biochem (2021). https://doi.org/10.1007/s13105-021-00787-z

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Keywords

  • Yes-associated protein
  • Sarcopenia
  • Ageing
  • Skeletal muscle
  • Cell signalling