Yap/Taz与衰老所致肌肉减少症自噬功能的关系

Q3 Medicine Nutrition and Healthy Aging Pub Date : 2023-03-02 DOI:10.3233/nha-220164
A. Sanjaya, R. Lesmana, H. Goenawan, I. Setiawan, N. Sylviana, Nova Yuni S. Pratiwi, Fitriya N. Dewi, U. Supratman
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引用次数: 0

摘要

背景:肌肉损失是与衰老相关的特征之一,对生活质量有重大影响。Hippo通路的效应子Yap/Taz被证明可以调节器官大小,并可能与衰老有关。我们推测,在衰老和少肌症期间,Yap/Taz调节可能在维持肌肉纤维大小或介导自噬功能方面发挥作用。目的:探讨少肌症及其与自噬和Yap/Taz表达的关系。此外,我们还探讨了衰老过程中骨骼肌组织自噬功能与Yap/Taz的关系。方法:采用16周和80周两组大鼠进行实验。采集比目鱼肌的骨骼肌组织,并定量Yap/Taz的mRNA表达和与自噬途径相关的基因。用抗Yap/Taz的抗体和自噬蛋白进行免疫印迹。在C2C12细胞系上使用巴氟霉素和维替泊芬来阐明自噬与Yap/Taz之间的相互作用。结果:发现老年大鼠比目鱼肌纤维表面积较小,并与Yap mRNA和蛋白表达增加有关。对自噬的抑制增加了Yap水平。然而,Yap/Taz功能的抑制并不影响骨骼肌的自噬。结论:根据目前的证据,Yap的增加与少肌症有矛盾的关系,而这种增加是由衰老引起的自噬流量减少引起的。
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The functional relationship of Yap/Taz with autophagy functions in sarcopenia associated with aging
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.
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来源期刊
Nutrition and Healthy Aging
Nutrition and Healthy Aging Agricultural and Biological Sciences-Food Science
CiteScore
1.70
自引率
0.00%
发文量
17
期刊介绍: Nutrition and Healthy Aging is an international forum for research on nutrition as a means of promoting healthy aging. It is particularly concerned with the impact of nutritional interventions on the metabolic and molecular mechanisms which modulate aging and age-associated diseases, including both biological responses on the part of the organism itself and its micro biome. Results emanating from both model organisms and clinical trials will be considered. With regards to the latter, the journal will be rigorous in only accepting for publication well controlled, randomized human intervention trials that conform broadly with the current EFSA and US FDA guidelines for nutritional clinical studies. The journal will publish research articles, short communications, critical reviews and conference summaries, whilst open peer commentaries will be welcomed.
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