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Axin-Mediated Regulation of Lifespan and Muscle Health in C. elegans Requires AMPK-FOXO Signaling
iScience ( IF 4.6 ) Pub Date : 2020-11-23 , DOI: 10.1016/j.isci.2020.101843
Avijit Mallick , Ayush Ranawade , Wouter van den Berg , Bhagwati P. Gupta

Aging is a significant risk factor for several diseases. Studies have uncovered multiple signaling pathways that modulate aging, including insulin/insulin-like growth factor-1 signaling (IIS). In Caenorhabditis elegans, the key regulator of IIS is DAF-16/FOXO. One of the kinases that affects DAF-16 function is the AMPK catalytic subunit homolog AAK-2. In this study, we report that PRY-1/Axin plays an essential role in AAK-2 and DAF-16-mediated regulation of life span. The pry-1 mutant transcriptome contains many genes associated with aging and muscle function. Consistent with this, pry-1 is strongly expressed in muscles, and muscle-specific overexpression of pry-1 extends life span, delays muscle aging, and improves mitochondrial morphology in AAK-2-DAF-16-dependent manner. Furthermore, PRY-1 is necessary for AAK-2 phosphorylation. Taken together, our data demonstrate that PRY-1 functions in muscles to promote the life span of animals. This study establishes Axin as a major regulator of muscle health and aging.



中文翻译:

毒素介导的秀丽隐杆线虫寿命和肌肉健康调节需要AMPK-FOXO信号传导

衰老是几种疾病的重要危险因素。研究发现了多种调节衰老的信号传导途径,包括胰岛素/ IGF-1信号传导(IIS)。在秀丽隐杆线虫中,IIS的关键调控因子是DAF-16 / FOXO。影响DAF-16功能的激酶之一是AMPK催化亚基同源物AAK-2。在这项研究中,我们报告PRY-1 / Axin在AAK-2和DAF-16介导的寿命调节中起着至关重要的作用。该撬-1突变体转录包含老化和肌肉功能相关的许多基因。与此相一致,pry-1在肌肉中强烈表达,并且pry-1的肌肉特异性过度表达以依赖AAK-2-DAF-16的方式延长寿命,延缓肌肉衰老并改善线粒体形态。此外,PRY-1对于AAK-2磷酸化是必需的。综上所述,我们的数据表明PRY-1在肌肉中具有促进动物寿命的功能。这项研究确立了Axin作为肌肉健康和衰老的主要调节剂。

更新日期:2020-12-03
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