The functional relationship of Yap/Taz with autophagy functions in sarcopenia associated with aging

Abstract

BACKGROUND: Muscle loss is one of the features associated with aging with significant impacts on the quality of life. Yap/Taz, the effectors of the Hippo pathway, was shown to regulate organ size and may be associated with aging. We postulate that Yap/Taz modulation may play a role in maintaining muscle fiber size or mediating the function of autophagy during aging and sarcopenia. OBJECTIVE: The research aim to explore sarcopenia and its relationship to autophagy and Yap/Taz expression. Additionally, we also explored the relationship of autophagy function and Yap/Taz on skeletal muscle tissue during aging. METHODS: We conducted experiments on two groups of rats kept at 16 and 80 weeks. Skeletal muscle tissue from the soleus muscle was harvested, and mRNA expression of Yap/Taz and genes associated with the autophagy pathway were quantified. Immunoblotting was done with antibodies against Yap/Taz and autophagy proteins. Bafilomycin and Verteporfin were used on the C2C12 cell line to elucidate the interaction between autophagy and Yap/Taz. RESULTS: Old rats were found to have a smaller fiber surface area of the soleus muscle and was associated with increased Yap mRNA and protein expression. The inhibition of autophagy increased Yap levels. However, the inhibition of Yap/Taz function did not affect autophagy in skeletal muscle. CONCLUSIONS: With current evidence, increased Yap was paradoxically associated with sarcopenia, and this increase was caused by the decreased autophagic flux caused by aging.