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.

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。